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Wang J, Yang J, Narang A, He J, Wolfgang C, Li K, Zheng L. Consensus, debate, and prospective on pancreatic cancer treatments. J Hematol Oncol 2024; 17:92. [PMID: 39390609 PMCID: PMC11468220 DOI: 10.1186/s13045-024-01613-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 09/25/2024] [Indexed: 10/12/2024] Open
Abstract
Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite the improvement of multi-modality treatment strategies, the prognosis of pancreatic cancer was not improved dramatically. For resectable or borderline resectable patients, the surgical strategy centered on improving R0 resection rate is consensus; however, the role of neoadjuvant therapy in resectable patients and the optimal neoadjuvant therapy of chemotherapy with or without radiotherapy in borderline resectable patients were debated. Postoperative adjuvant chemotherapy of gemcitabine/capecitabine or mFOLFIRINOX is recommended regardless of the margin status. Chemotherapy as the first-line treatment strategy for advanced or metastatic patients included FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan was the only standard of care second-line therapy. Immunotherapy is an innovative therapy although anti-PD-1 antibody is currently the only agent approved by for MSI-H, dMMR, or TMB-high solid tumors, which represent a very small subset of pancreatic cancers. Combination strategies to increase the immunogenicity and to overcome the immunosuppressive tumor microenvironment may sensitize pancreatic cancer to immunotherapy. Targeted therapies represented by PARP and KRAS inhibitors are also under investigation, showing benefits in improving progression-free survival and objective response rate. This review discusses the current treatment modalities and highlights innovative therapies for pancreatic cancer.
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Affiliation(s)
- Junke Wang
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA
- The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Jie Yang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan, China
- Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Amol Narang
- Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA
- The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Jin He
- Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA
- The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Christopher Wolfgang
- Department of Surgery, New York University School of Medicine and NYU-Langone Medical Center, New York, NY, USA
| | - Keyu Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
- Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA.
- The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
| | - Lei Zheng
- Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA.
- The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
- The Multidisciplinary Gastrointestinal Cancer Laboratories Program, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
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Demaziere A, Mourgues C, Lambert C, Trevis S, Bertucat H, Grange I, Pezet D, Sautou V, Jary M, Gagnière J. French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel versus gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients. Ther Adv Med Oncol 2024; 16:17588359241259635. [PMID: 38882442 PMCID: PMC11179525 DOI: 10.1177/17588359241259635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 05/20/2024] [Indexed: 06/18/2024] Open
Abstract
Context In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the institutions. Objectives GEM-NAB conduct a French multi-institutional cost-effectiveness analysis of GEM-NAB versus gemcitabine alone (GEM) as second-line treatment in pancreatic cancer patients. Design All the unresected metastatic pancreatic ductal adenocarcinoma (PDAC) consecutive patients who received GEM-NAB (institution 1) or GEM alone (institutions 2 and 3) as second-line treatment after failure of a 5-fluorouracil based systemic chemotherapy regimen were screened. Methods This study was conducted from the French national healthcare insurance perspective. The primary endpoint was the overall survival (OS) expressed in months, calculated from the date of the first second-line chemotherapy administration to death. Only direct (medical and non-medical) costs have been considered for this analysis. Data were collected retrospectively in one university hospital and two general hospitals. Results The OS was significantly improved in patients receiving GEM-NAB (hazard ratio: 0.54, 95% confidence interval: 0.38-0.77, p = 0.001), with a median OS of 6.2 months (versus 4.1 months in patients receiving GEM alone). Taking into account the cost of GEM-NAB which was afforded by each institution, the incremental cost-effectiveness ratio was €1,449,231 by year of life (€40,256 per patient). In both groups, most of the costs were attributable to readmissions and outpatient chemotherapy administration. Conclusion The issues of the article is based on the trade-off between the benefit in terms of OS of patients treated with GEM-NAB, which is minor (a gain of 2 months of survival, with an accumulated rate of grade ⩾ 3 non-hematological adverse effects) and the additional institutional cost (€25k per year of life for each patient treated). The debate is complex and refers to an ethical component, which is the cost of human life when no other therapeutic alternative is offered to the patient.
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Affiliation(s)
- Amaury Demaziere
- Department of Pharmacy, CHU Clermont-Ferrand, 58 Rue Montalembert, Clermont-Ferrand 63000, France
| | - Charline Mourgues
- Biostatistics Unit, DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Céline Lambert
- Biostatistics Unit, DRCI, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Sophie Trevis
- Department of Pharmacy, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | | | - Isabelle Grange
- Department of Pharmacy, Hospital of Le Puy-en-Velay, Le Puy-en-Velay, France
| | - Denis Pezet
- Department of Digestive and Hepatobiliary Surgery, CHU Clermont-Ferrand, Clermont-Ferrand, France
- U1071 Inserm, Clermont-Auvergne University, Clermont-Ferrand, France
| | - Valérie Sautou
- Department of Pharmacy, CHU Clermont-Ferrand, Clermont-Ferrand, France
- CNRS, SIGMA Clermont-Ferrand, ICCF, Clermont-Auvergne University, Clermont-Ferrand, France
| | - Marine Jary
- Department of Digestive and Hepatobiliary Surgery, CHU Clermont-Ferrand, Clermont-Ferrand, France
- U1071 Inserm, Clermont-Auvergne University, Clermont-Ferrand, France
| | - Johan Gagnière
- Department of Digestive and Hepatobiliary Surgery, CHU Clermont-Ferrand, Clermont-Ferrand, France
- U1071 Inserm, Clermont-Auvergne University, Clermont-Ferrand, France
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Elechalawar CK, Gulla SK, Roy RV, Means N, Zhang Y, Asifa S, Robertson DJ, Xu C, Bhattacharya R, Mukherjee P. Biodistribution and therapeutic efficacy of a gold nanoparticle-based targeted drug delivery system against pancreatic cancer. Cancer Lett 2024; 589:216810. [PMID: 38494151 PMCID: PMC11793163 DOI: 10.1016/j.canlet.2024.216810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 02/22/2024] [Accepted: 03/07/2024] [Indexed: 03/19/2024]
Abstract
Pancreatic cancer is characterized by desmoplasia; crosstalk between pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) leads to the deposition of extracellular matrix proteins in the tumor environment resulting in poor vascularity. Targeting either PCCs or PSCs individually has produced mixed results, and there is currently no effective strategy to target both cell types simultaneously. Previously, we demonstrated, through in vitro cell culture experiments, that a specific gold nanoparticle-based nanoformulation containing the anti-EGFR antibody cetuximab (C225) as a targeting agent and gemcitabine as a chemotherapeutic agent effectively targets both PCCs and PSCs simultaneously. Herein, we extend our studies to test the ability of these in vitro tested nano formulations to inhibit tumor growth in an orthotopic co-implantation model of pancreatic cancer in vivo. Orthotopic tumors were established by co-implantation of equal numbers of PCCs and PSCs in the mouse pancreas. Among the various formulations tested, 5 nm gold nanoparticles coated with gemcitabine, cetuximab and poly-ethylene glycol (PEG) of molecular weight 1000 Da, which we named ACGP441000, demonstrated optimal efficacy in inhibiting tumor growth. The current study reveals an opportunity to target PCCs and PSCs simultaneously, by exploiting their overexpression of EGFR as a target, in order to inhibit pancreatic cancer growth.
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Affiliation(s)
- Chandra Kumar Elechalawar
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Suresh Kumar Gulla
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Ram Vinod Roy
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Nicolas Means
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Yushan Zhang
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Sima Asifa
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - David J Robertson
- Department of Chemistry and University of Missouri Research Reactor, University of Missouri, Columbia, MO 65211, USA
| | - Chao Xu
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Resham Bhattacharya
- Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Priyabrata Mukherjee
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
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Treatment Outcomes and Prognostic Factors of Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy after Modified FOLFIRINOX in Unresectable Pancreatic Cancer. Cancers (Basel) 2023; 15:cancers15020358. [PMID: 36672308 PMCID: PMC9857205 DOI: 10.3390/cancers15020358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/26/2022] [Accepted: 01/03/2023] [Indexed: 01/06/2023] Open
Abstract
Outcomes and prognostic factors of second-line gemcitabine plus nab-paclitaxel (GnP) after modified FOLFIRINOX (mFFX) for unresectable pancreatic cancer were unclear. We retrospectively analyzed consecutive patients with unresectable pancreatic cancer treated with GnP after first-line mFFX treatment between March 2015 and March 2022 at our hospital. A total of 103 patients were included. Median overall survival (OS) from the start of first-line and second-line treatments was 14.9 months and 7.2 months, respectively. Median progression-free survival (PFS) was 3.6 months. Performance status, modified Glasgow prognostic score, and neutrophil-to-lymphocyte ratio were independently associated with OS. Our prognostic model using these parameters classifies patients into good (n = 70) and poor (n = 33) prognosis groups. Median OS and PFS were longer in the good prognosis group than in the poor prognosis group (OS: 9.3 vs. 3.8 months, p < 0.01; PFS: 4.1 vs. 2.3 months, p < 0.01). Grade 3/4 adverse events were observed in 70.9% of patients, with neutropenia being the most frequent. While GnP as second-line treatment was well-tolerated, efficacy of second-line gemcitabine plus nab-paclitaxel was notably limited, particularly in the poor prognosis group.
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Sardar M, Recio-Boiles A, Mody K, Karime C, Chandana SR, Mahadevan D, Starr J, Jones J, Borad M, Babiker H. Pharmacotherapeutic options for pancreatic ductal adenocarcinoma. Expert Opin Pharmacother 2022; 23:2079-2089. [PMID: 36394449 DOI: 10.1080/14656566.2022.2149322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.
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Affiliation(s)
- Muhammad Sardar
- Division of Hematology-Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Az, USA
| | - Alejandro Recio-Boiles
- Division of Hematology-Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Az, USA
| | - Kabir Mody
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | | | | | - Daruka Mahadevan
- Division of Hematology and Oncology, Department of Medicine, University of Texas, San Antonio, Texas, USA
| | - Jason Starr
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | - Jeremy Jones
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | - Mitesh Borad
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Phoenix, AZ, USA
| | - Hani Babiker
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
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Aung KL, McWhirter E, Welch S, Wang L, Lovell S, Stayner LA, Ali S, Malpage A, Makepeace B, Ramachandran M, Jang GH, Gallinger S, Zhang T, Stockley TL, Fischer SE, Dhani N, Hedley D, Knox JJ, Siu LL, Goodwin R, Bedard PL. A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma. J Gastrointest Oncol 2022; 13:3216-3226. [PMID: 36636049 PMCID: PMC9830369 DOI: 10.21037/jgo-22-86] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 08/12/2022] [Indexed: 11/06/2022] Open
Abstract
Background Mitogen-activated protein kinase kinase (MEK) is activated by mutated KRAS in >90% of pancreatic ductal adenocarcinoma (PDAC). MEK and focal adhesion kinase (FAK) are frequently co-activated in PDAC providing a rationale for combining trametinib, an oral allosteric MEK1/2 inhibitor, with GSK2256098, an oral FAK inhibitor. Methods Advanced PDAC patients whose disease progressed after first line palliative chemotherapy were treated with GSK2256098 250 mg twice daily and trametinib 0.5 mg once daily orally. The primary endpoint was clinical benefit (CB; complete response, partial response, or stable disease ≥24 weeks). Twenty-four patients were planned to enroll using a 2-stage minimax design (P0=0.15, P1=0.40; alpha =0.05, power 0.86). The combination would be considered inactive if 2/12 or fewer patients achieved CB at the end of stage 1, and would be considered active if >7/24 response-evaluable patients achieved CB by the end of stage 2. Serial blood samples were collected for circulating tumor DNA (ctDNA) mutation profiling. Results Sixteen patients were enrolled and 11 were response evaluable. Of those 11, 10 had progressive disease as best tumor response and one had stable disease for 4 months. No treatment related grade ≥3 adverse events (AEs) were observed. The median progression free survival (PFS) was 1.6 (95% CI: 1.5-1.8) months and the median overall survival (OS) was 3.6 (95% CI: 2.7-not reached) months. One response-inevaluable patient achieved clinical stability for 5 months with reduction in CA19-9 and ctDNA levels with a MAP2K1 treatment resistance mutation detected in ctDNA at clinical progression. Conclusions The combination of GSK2256098 and trametinib was well tolerated but was not active in unselected advanced PDAC.
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Affiliation(s)
- Kyaw L. Aung
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | | | | | - Lisa Wang
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Sophia Lovell
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Lee-Anne Stayner
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Saara Ali
- Ottawa Hospital Cancer Centre, Ottawa, ON, Canada
| | - Anne Malpage
- London Health Science Centre, London, ON, Canada
| | | | | | - Gun Ho Jang
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | | | - Tong Zhang
- Advanced Molecular Diagnostics Laboratory, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Tracy L. Stockley
- Advanced Molecular Diagnostics Laboratory, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Divison of Laboratory Genetics, Laboratory Medicine Program, Department of Pathology, University Health Network, Toronto, ON, Canada;,Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada
| | - Sandra E. Fischer
- Department of Pathology, University Health Network, Toronto, ON, Canada
| | - Neesha Dhani
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - David Hedley
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Jennifer J. Knox
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Lillian L. Siu
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | | | - Philippe L. Bedard
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;,Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada
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Winer A, Dotan E. Treatment Paradigms for Older Adults with Pancreatic Cancer: a Nuanced Approach. Curr Treat Options Oncol 2021; 22:104. [PMID: 34596801 DOI: 10.1007/s11864-021-00892-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2021] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is increasing in incidence in the USA. This disease disproportionately affects older adults, and as the percentage of adults > 65 years old increases with the aging of the baby boomers, the prevalence is expected to rise over the coming decade. These patients are often more susceptible to disease-related symptoms and have less ability to withstand both cancer and treatment-related side effects. Therefore, it is imperative that treating physicians thoughtfully consider their recommended treatment approach towards this vulnerable patient population. This review focuses on the current state of research of older adults with pancreatic adenocarcinoma, highlighting deficiencies in the representation of this patient population in clinical trials. It is vital that the treating physicians take a nuanced approach towards therapy of localized and metastatic disease in geriatric patients. A one size fits all treatment algorithm is no longer appropriate in any cancer patient, let alone the elders who are particularly vulnerable to developing treatment-related toxicities. To help guide therapy decisions, it is important to perform a comprehensive geriatric assessment which may uncover unexpected frailty and lead to a change in the recommended treatment approach. In this way, we can support older adults during therapy for this aggressive malignancy and provide optimal care.
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Affiliation(s)
- Arthur Winer
- Department of Medical Oncology, Inova Schar Cancer Institute, 8081 Innovation Park Drive, Fairfax, VA, 22031, USA.
| | - Efrat Dotan
- Department of Medical Oncology, Fox Chase Cancer, Philadelphia, PA, USA
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8
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Pijnappel EN, Wassenaar NPM, Gurney-Champion OJ, Klaassen R, van der Lee K, Pleunis-van Empel MCH, Richel DJ, Legdeur MC, Nederveen AJ, van Laarhoven HWM, Wilmink JW. Phase I/II Study of LDE225 in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Cancer. Cancers (Basel) 2021; 13:4869. [PMID: 34638351 PMCID: PMC8507646 DOI: 10.3390/cancers13194869] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 09/17/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Desmoplasia is a central feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumor stroma. We investigated the combined use of LDE225 and chemotherapy to treat PDAC patients. METHODS This was a multi-center, phase I/II study for patients with metastatic PDAC establishing the maximum tolerated dose of LDE225 co-administered with gemcitabine and nab-paclitaxel (phase I) and evaluating the efficacy and safety of the treatment combination after prior FOLFIRINOX treatment (phase II). Tumor microenvironment assessment was performed with quantitative MRI using intra-voxel incoherent motion diffusion weighted MRI (IVIM-DWI) and dynamic contrast-enhanced (DCE) MRI. RESULTS The MTD of LDE225 was 200 mg once daily co-administered with gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2. In phase II, six therapy-related grade 4 adverse events (AE) and three grade 5 were observed. In 24 patients, the target lesion response was evaluable. Three patients had partial response (13%), 14 patients showed stable disease (58%), and 7 patients had progressive disease (29%). Median overall survival (OS) was 6 months (IQR 3.9-8.1). Blood plasma fraction (DCE) and diffusion coefficient (IVIM-DWI) significantly increased during treatment. Baseline perfusion fraction could predict OS (>222 days) with 80% sensitivity and 85% specificity. CONCLUSION LDE225 in combination with gemcitabine and nab-paclitaxel was well-tolerated in patients with metastatic PDAC and has promising efficacy after prior treatment with FOLFIRINOX. Quantitative MRI suggested that LDE225 causes increased tumor diffusion and works particularly well in patients with poor baseline tumor perfusion.
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Affiliation(s)
- Esther N. Pijnappel
- Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (E.N.P.); (R.K.); (K.v.d.L.); (D.J.R.); (H.W.M.v.L.)
| | - Nienke P. M. Wassenaar
- Cancer Center Amsterdam, Department of Radiology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (N.P.M.W.); (O.J.G.-C.); (A.J.N.)
| | - Oliver J. Gurney-Champion
- Cancer Center Amsterdam, Department of Radiology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (N.P.M.W.); (O.J.G.-C.); (A.J.N.)
| | - Remy Klaassen
- Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (E.N.P.); (R.K.); (K.v.d.L.); (D.J.R.); (H.W.M.v.L.)
| | - Koen van der Lee
- Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (E.N.P.); (R.K.); (K.v.d.L.); (D.J.R.); (H.W.M.v.L.)
| | | | - Dick J. Richel
- Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (E.N.P.); (R.K.); (K.v.d.L.); (D.J.R.); (H.W.M.v.L.)
| | - Marie C. Legdeur
- Department of Medical Oncology, Medisch Spectrum Twente, Twente, 7512 Enschede, The Netherlands; (M.C.H.P.-v.E.); (M.C.L.)
| | - Aart J. Nederveen
- Cancer Center Amsterdam, Department of Radiology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (N.P.M.W.); (O.J.G.-C.); (A.J.N.)
| | - Hanneke W. M. van Laarhoven
- Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (E.N.P.); (R.K.); (K.v.d.L.); (D.J.R.); (H.W.M.v.L.)
| | - Johanna W. Wilmink
- Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, 1012 Amsterdam, The Netherlands; (E.N.P.); (R.K.); (K.v.d.L.); (D.J.R.); (H.W.M.v.L.)
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Blomstrand H, Batra A, Cheung WY, Elander NO. Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer. World J Clin Oncol 2021; 12:787-799. [PMID: 34631442 PMCID: PMC8479347 DOI: 10.5306/wjco.v12.i9.787] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/09/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.
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Affiliation(s)
- Hakon Blomstrand
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
| | - Atul Batra
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Winson Y Cheung
- Department of Oncology, University of Calgary, Calgary T2N 4N1, Canada
| | - Nils Oskar Elander
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
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10
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Lee-Ying R, Ahmed O, Ahmed S, Ahmed S, Bathe OF, Brunet B, Dawson L, Davies J, Gordon V, Hebbard P, Kasnik J, Kim CA, Le D, Lee MKC, Lim H, McGhie JP, Mulder K, Park J, Renouf D, Tam V, Visser R, Wong RPW, Zaidi A, Doll C. Report from the 21st Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; 20-21 September 2019. Curr Oncol 2021; 28:3629-3648. [PMID: 34590606 PMCID: PMC8482207 DOI: 10.3390/curroncol28050310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/18/2021] [Accepted: 09/18/2021] [Indexed: 12/12/2022] Open
Abstract
The 21st annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, 20-21 September 2019. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists, pathologists, radiologists, and allied health care professionals such as dietitians and nurses participated in presentation and discussion sessions to develop the recommendations presented here. This consensus statement addresses current issues in the management of hepato-pancreato-biliary (HPB) cancers.
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Affiliation(s)
- Richard Lee-Ying
- Tom Baker Cancer Center, Alberta Health Service, Calgary, AB T2N 4N2, Canada; (V.T.); (C.D.)
| | - Osama Ahmed
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada; (O.A.); (S.A.); (B.B.); (D.L.); (A.Z.)
| | - Shahid Ahmed
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada; (O.A.); (S.A.); (B.B.); (D.L.); (A.Z.)
| | - Shahida Ahmed
- Department of Oncology, Cancer Care Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (V.G.); (P.H.); (C.A.K.); (J.P.); (R.P.W.W.)
| | - Oliver F. Bathe
- Surgical Oncology, Arnie Charbonneau Cancer Institute, Calgary, AB T2N 4Z6, Canada;
| | - Bryan Brunet
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada; (O.A.); (S.A.); (B.B.); (D.L.); (A.Z.)
| | - Laura Dawson
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada;
| | - Janine Davies
- Department of Oncology, British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (J.D.); (M.K.C.L.); (H.L.); (D.R.)
| | - Valerie Gordon
- Department of Oncology, Cancer Care Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (V.G.); (P.H.); (C.A.K.); (J.P.); (R.P.W.W.)
| | - Pamela Hebbard
- Department of Oncology, Cancer Care Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (V.G.); (P.H.); (C.A.K.); (J.P.); (R.P.W.W.)
| | - Jessica Kasnik
- Cross Cancer Institute, Alberta Health Services, Edmonton, AB T5G 1Z2, Canada; (J.K.); (K.M.)
| | - Christina A. Kim
- Department of Oncology, Cancer Care Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (V.G.); (P.H.); (C.A.K.); (J.P.); (R.P.W.W.)
| | - Duc Le
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada; (O.A.); (S.A.); (B.B.); (D.L.); (A.Z.)
| | - Michael K. C. Lee
- Department of Oncology, British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (J.D.); (M.K.C.L.); (H.L.); (D.R.)
| | - Howard Lim
- Department of Oncology, British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (J.D.); (M.K.C.L.); (H.L.); (D.R.)
| | - John Paul McGhie
- Department of Oncology, British Columbia Cancer Agency, Victoria, BC V8R 4S1, Canada;
| | - Karen Mulder
- Cross Cancer Institute, Alberta Health Services, Edmonton, AB T5G 1Z2, Canada; (J.K.); (K.M.)
| | - Jason Park
- Department of Oncology, Cancer Care Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (V.G.); (P.H.); (C.A.K.); (J.P.); (R.P.W.W.)
| | - Daniel Renouf
- Department of Oncology, British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (J.D.); (M.K.C.L.); (H.L.); (D.R.)
| | - Vincent Tam
- Tom Baker Cancer Center, Alberta Health Service, Calgary, AB T2N 4N2, Canada; (V.T.); (C.D.)
| | - Robin Visser
- Department of Surgery, University of Manitoba, Winnipeg, MB R3E 0V9, Canada;
| | - Ralph P. W. Wong
- Department of Oncology, Cancer Care Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (V.G.); (P.H.); (C.A.K.); (J.P.); (R.P.W.W.)
| | - Adnan Zaidi
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada; (O.A.); (S.A.); (B.B.); (D.L.); (A.Z.)
| | - Corinne Doll
- Tom Baker Cancer Center, Alberta Health Service, Calgary, AB T2N 4N2, Canada; (V.T.); (C.D.)
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Hayuka K, Okuyama H, Murakami A, Okita Y, Nishiuchi T, Okano K, Suzuki Y, Tsuji A. Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis. Chemotherapy 2021; 66:58-64. [PMID: 34284397 DOI: 10.1159/000517244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/09/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. METHODS Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. RESULTS The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). CONCLUSIONS GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.
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Affiliation(s)
- Kotone Hayuka
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan,
| | - Hiroyuki Okuyama
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Akitsu Murakami
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Yoshihiro Okita
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Takamasa Nishiuchi
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Kagawa University, Takamatsu, Japan
| | - Yasuyuki Suzuki
- Department of Gastroenterological Surgery, Kagawa University, Takamatsu, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
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12
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Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. Biomolecules 2021; 11:biom11060780. [PMID: 34067288 PMCID: PMC8224606 DOI: 10.3390/biom11060780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/20/2021] [Accepted: 05/20/2021] [Indexed: 11/17/2022] Open
Abstract
FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by several biases. In order to overcome these biases, we took advantage of matching-adjusted indirect comparison (MAIC), that allows an indirect comparison by reducing cross-trial differences, and compared data from 268 patients treated with GN in a real-world setting with data from the 171 patients included in the FFX arm of the PRODIGE trial. Survival outcomes did not differ between the two populations. Overall survival was 11.1 months for both treatments (hazard ratio (HR) of FFX 1.10, 95% confidence interval (CI) 0.81–1.49; p = 0.527). Progression-free survival was 6.0 months with GN and 6.4 months with FFX (HR of FFX 1.11, 95% CI 0.82–1.50; p = 0.520). On the other hand, we observed a difference in the toxicity profiles: grade 3/4 anemia was more frequent with GN, whereas a higher occurrence of grade 3/4 vomiting and diarrhea was reported with FFX. FFX and GN show an equivalent efficacy but different safety profiles in the first-line therapy of metastatic pancreatic cancer. Searching for reliable predictive biomarkers is advised in order to improve therapeutic strategy in metastatic PC.
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13
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Yeh C, Bates SE. Two decades of research toward the treatment of locally advanced and metastatic pancreatic cancer: Remarkable effort and limited gain. Semin Oncol 2021; 48:34-46. [PMID: 33712267 DOI: 10.1053/j.seminoncol.2021.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 01/20/2021] [Indexed: 01/04/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is diagnosed at the locally advanced or metastatic stage in approximately 80% of cases. Relative to other tumor types, progress in the treatment of this disease has been painfully slow. While agents targeting DNA repair have proven successful in a subset of patients, the majority of PDACs do not exhibit validated molecular targets. Hence, conventional chemotherapy remains at the forefront of therapy for this disease. In this review, we study two decades of efforts to improve upon the gemcitabine backbone - 67 phase II and III trials enrolling 16,446 patients - that culminated in the approvals of gemcitabine/nab-paclitaxel (Gem/NabP) and FOLFIRINOX. Today, these remain gold standards for the first-line treatment of locally advanced unresectable and metastatic PDAC, while ongoing efforts focus on improving upon the Gem/NabP backbone. Because real world data often do not reflect the data of randomized controlled trials (RCTs), we also summarize the retrospective evidence comparing the efficacy of Gem/NabP and FOLFIRINOX in the first-line setting - 29 studies reporting a median overall survival of 10.7 and 9.1 months for FOLFIRINOX and Gem/NabP, respectively. These values are surprisingly comparable to those reported by the pivotal RCTs at 11.1 and 8.5 months. Finally, there is a paucity of RCT data regarding the efficacy of second-line therapy. Hence, we conclude this review by summarizing the data that ultimately demonstrate a small but significant survival benefit of second-line therapy with Gem/NabP or FOLFIRINOX. Collectively, these studies describe the long journey, the steady effort, and the myriad lessons to be learned from 20 years of PDAC trials to inform strategies for success in clinical trials moving forward.
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Affiliation(s)
- Celine Yeh
- Department of Medicine, Columbia University Irving Medical Center, New York, NY
| | - Susan E Bates
- James J. Peters VA Medical Center, Bronx, NY; Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY.
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14
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Zhang J, Wang W, Zhou Y, Yang J, Xu J, Xu Z, Xu B, Yan L, Cheng XD, Li M, Qin JJ. Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice. Front Pharmacol 2020; 11:457. [PMID: 32322210 PMCID: PMC7157903 DOI: 10.3389/fphar.2020.00457] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 03/24/2020] [Indexed: 12/14/2022] Open
Abstract
Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and effective anti-PC therapeutic agents. We have recently identified a novel marine-derived natural product terphenyllin with potent anti-PC activity. The present study was designed to investigate the efficacy and mechanisms of action of terphenyllin in several human PC cell lines and an orthotopic PC mouse model. The results showed that terphenyllin significantly inhibited the viability of all PC cell lines with minimal effects on a normal human pancreatic cell line (HPNE). We next demonstrated the effects of terphenyllin on colony formation, apoptosis, migration, and invasion in both Panc1 and HPAC cell lines in a concentration-dependent manner. Terphenyllin also suppressed the tumor growth and metastasis in the Panc1 orthotopic mouse model. We further showed the profound effects of terphenyllin on the expression of apoptosis-associated proteins, including Bax, Bad, Puma, BimL, Bcl-2, phos-Bcl-2 (Ser70), Bcl-xL, caspase 7, and PARP, which contributed to its anti-PC activity. In summary, terphenyllin suppressed the PC cell growth and metastasis in vitro and in vivo and may be developed as an anti-PC therapeutic agent in the future.
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Affiliation(s)
- Jia Zhang
- Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, China
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Weiyi Wang
- Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, China
| | - Yuan Zhou
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jing Yang
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jingli Xu
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiyuan Xu
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou, China
| | - Beihua Xu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Li Yan
- School of Pharmacy, Naval Medical University, Shanghai, China
| | - Xiang-Dong Cheng
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou, China
| | - Minghua Li
- Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, China
| | - Jiang-Jiang Qin
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou, China
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15
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de Jesus VHF, Camandaroba MPG, Calsavara VF, Riechelmann RP. Systematic review and meta-analysis of gemcitabine-based chemotherapy after FOLFIRINOX in advanced pancreatic cancer. Ther Adv Med Oncol 2020; 12:1758835920905408. [PMID: 32165927 PMCID: PMC7052451 DOI: 10.1177/1758835920905408] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 01/14/2020] [Indexed: 12/11/2022] Open
Abstract
Background There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity. Methods We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions. Results Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p = 0.038) and DCR (53.5 versus 30.5%; p < 0.001) compared with single-agent gemcitabine. Median PFS ranged from 1.9 to 6.4 months and numerically favored gemcitabine plus nab-paclitaxel. Conclusions Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).
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Affiliation(s)
- Victor H F de Jesus
- Medical Oncology Department, A.C. Camargo Cancer Center, Rua Prof. Antônio Prudente, 211, São Paulo, 01509-010, Brazil
| | | | - Vinicius F Calsavara
- Department of Epidemiology and Statistics - International Research Center (CIPE), A.C. Camargo Cancer Center, São Paulo, Brazil
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Abstract
Chemotherapy is an important part of multimodality pancreatic cancer treatment. After curative resection, adjuvant chemotherapy can significantly improve disease free survival and overall survival. The current standard of care is six months adjuvant chemotherapy with modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) in patients fit enough for this protocol, otherwise six months of gemcitabine and capecitabine based on the European Study Group for Pancreatic Cancer (ESPAC)-4 study. In patients with metastatic disease, combination chemotherapy according to the FOLFIRINOX protocol or with gemcitabine plus nab-paclitaxel is an important improvement to gemcitabine monotherapy that was the standard for many years. Patients not fit for combination chemotherapy however may still benefit from gemcitabine. Patients with good performance status may benefit from second-line chemotherapy. Chemoradiation has long been used in locally advanced pancreatic cancer but is now tempered following the LAP07 study. This trial showed no difference in overall survival in those patients with stable disease after four months of gemcitabine (with or without erlotinib) randomized to either continuation of gemcitabine therapy or chemoradiation (54Gy with capecitabine). As an alternative to radiation, other forms local therapies including radiofrequency ablation, irreversible electroporation, high-intensity focused ultrasound, microwave ablation and local anti-KRAS therapy (using siG12D-LODER) are currently under investigation. Given the systemic nature of pancreas cancer from an early stage, the success of any local approach other than complete surgical resection (with adjuvant systemic therapy) is likely to be very limited. In patients with locally advanced, irresectable cancer, chemotherapy may offer the chance for secondary resection with a survival similar to patients with primary resectable disease. Downstaging regimens need to be evaluated in prospective randomized trials in order to make firm recommendations. Selection of patient groups for specific therapy including cytotoxics is becoming a reality using assays based on drug cellular transport and metabolism, and molecular signatures. Going forward, high throughput screening of different chemotherapy agents using molecular signatures based on patients' derived organoids holds considerable promise.
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17
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Vogl UM, Andalibi H, Klaus A, Vormittag L, Schima W, Heinrich B, Kafka A, Winkler T, Öhler L. Nab-paclitaxel and gemcitabine or FOLFIRINOX as first-line treatment in patients with unresectable adenocarcinoma of the pancreas: does sequence matter? BMC Cancer 2019; 19:28. [PMID: 30621630 PMCID: PMC6325849 DOI: 10.1186/s12885-018-5240-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 12/21/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Locally advanced or metastatic adenocarcinoma of the pancreas remains - despite the implementation of new chemotherapy protocols - a disease with short overall survival (OS). METHODS Eighty-three patients were treated with locally advanced or metastatic adenocarcinoma of the pancreas with either FOLFIRINOX or nab-Paclitxel and Gemcitabine (nabPGem) as first- or second line therapy. We analysed the outcome for OS and progression-free survival (PFS) in terms of treatment regimen and sequence. RESULTS The majority of patients presented in good performance status (PS) with a median age of 68 years. Fourty-two patients received FOLFIRINOX as first-line therapy, 41 patients were treated with nabPGem as first line therapy. Forty-eight patients received both treatments. The OS of all 83 patients was 12.6 months (95% CI: 10.7-14.6), resulting in a 1-year OS of 54%. Forty-eight patients received FOLFIRINOX followed by nabPGem or vice versa. There was no significant difference in OS or PFS for either of the two sequences (p = 0.9). The OS for FOLFIRINOX followed by nabPGem or nabPGem followed by FOLFIRINOX was 13.7 months (95% CI: 12.6-14.7) and 13.8 months (95% CI: 8.6-19), respectively. CONCLUSIONS The sequence FOLFIRINOX followed by nab-Paclitaxel and Gemcitabine or vice versa lead to an equal OS outcome.
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Affiliation(s)
- Ursula M. Vogl
- Department of Internal Medicine II, Oncology, Barmherzige Schwestern Wien, Stumpergasse 13, 1060 Vienna, Austria
| | - Haleh Andalibi
- Department of Internal Medicine II, Oncology, Barmherzige Schwestern Wien, Stumpergasse 13, 1060 Vienna, Austria
| | - Alexander Klaus
- Department of Surgery, Barmherzige Schwestern Wien, Vienna, Austria
| | - Laurenz Vormittag
- Department of Internal Medicine I, Oncology, Sankt Josef Krankenhaus, Vienna, Austria
| | - Wolfgang Schima
- Department of Diagnostic and Interventional Radiology, Barmherzige Schwestern Krankenhaus Wien, Goettlicher Heiland Krankenhaus and Sankt Josef Krankenhaus, Vienna, Austria
| | - Bettina Heinrich
- Department of Internal Medicine I, Oncology, Sankt Josef Krankenhaus, Vienna, Austria
| | - Alice Kafka
- Department of Internal Medicine I, Oncology, Sankt Josef Krankenhaus, Vienna, Austria
| | - Thomas Winkler
- Department of Internal Medicine I, Oncology, Sankt Josef Krankenhaus, Vienna, Austria
| | - Leopold Öhler
- Department of Internal Medicine II, Oncology, Barmherzige Schwestern Wien, Stumpergasse 13, 1060 Vienna, Austria
- Department of Internal Medicine I, Oncology, Sankt Josef Krankenhaus, Vienna, Austria
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18
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de Jesus VHF, Camandaroba MPG, Donadio MDS, Cabral A, Muniz TP, de Moura Leite L, Sant'Ana LF. Retrospective analysis of efficacy and safety of Gemcitabine-based chemotherapy in patients with metastatic pancreatic adenocarcinoma experiencing disease progression on FOLFIRINOX. J Gastrointest Oncol 2018; 9:806-819. [PMID: 30505579 DOI: 10.21037/jgo.2018.06.08] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Metastatic pancreatic adenocarcinoma (MPA) represents a highly lethal condition. Despite the improvements seen with FOLFIRINOX, there is no randomized data to guide treatment selection beyond this regimen. We aimed to evaluate the outcomes of patients with MPA progressing on FOLFIRINOX who were treated with Gemcitabine-based chemotherapy afterwards. Methods We included patients aged 18 years or older, treated for MPA with FOLFIRINOX in the first-line setting and who experienced disease progression, with Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and treated with at least one cycle of Gemcitabine-based chemotherapy in second or further lines of treatment. We used descriptive statistics to characterize the study population and Cox proportional-hazards models to describe factors associated with survival. As an exploratory analysis, we compared the outcomes of patients treated with single-agent Gemcitabine with those of patients undergoing Gemcitabine-based polychemotherapy. Results The study population consisted of 42 patients. Median age was 59 years and 78.6% of patients presented ECOG 0-1. Thirty-three patients (78.6%) were treated with Gemcitabine-based chemotherapy in the second-line setting and 27 patients (64.3%) were treated with single-agent Gemcitabine. Objective response rate and disease control rate were 2.4% and 33.4%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 2.9 and 5.5 months, respectively. Six-month PFS and OS rates were 19.2% and 46.2%, respectively. We observed no significant difference in OS according to the type of Gemcitabine-based chemotherapy, despite numerically improved disease control rate and PFS for those treated with Gemcitabine-based polychemotherapy. In multivariate analysis, ECOG 2 (vs. ECOG 0-1) was the only factor significantly associated with inferior PFS and OS. Conclusions a subgroup of patients with MPA derives benefit from treatment with Gemcitabine-based regimens after FOLFIRINOX. There is a suggestion that Gemcitabine-based combinations, in particular Gemcitabine plus Nab-Paclitaxel, provide superior outcomes compared to single-agent Gemcitabine. Additionally, treatment in this setting should be offered carefully to patients with ECOG 2, as they present shorter survival and increased risk of toxicity.
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Affiliation(s)
| | | | | | - Audrey Cabral
- Medical Oncology Department, A.C. Camargo Cancer Center, São Paulo, SP, Brazil
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Second-Line Treatment for Advanced Pancreatic Adenocarcinoma: Is There a Role for Gemcitabine? J Gastrointest Cancer 2018; 50:860-866. [PMID: 30175393 DOI: 10.1007/s12029-018-0166-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
PURPOSE Advanced pancreatic adenocarcinoma (PA) is an aggressive disease that has poor prognosis and frequently interferes with patient's quality of life. There has been progress in first-line regimens; however, there is no standard second-line regimen. The aim of this study is to analyze second-line gemcitabine after first-line fluorouracil (FU) + leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX) regimen. METHODS This study included consecutive patients with advanced PA treated at Hospital Sirio-Libanês from 2011 to 2016. The patients received FOLFIRINOX as first-line treatment and upon progression, received gemcitabine alone. Survival analysis was performed using the Kaplan-Meier method. RESULTS A total of 54 patients were evaluated. Most patients were male (61.1%) and most had an ECOG performance status of 0 or 1 prior to the beginning of second-line treatment (66.6%). The mean number of gemcitabine cycles was 3.4. Most patients had disease progression as the best response to treatment (75.9%), 11.1% had stable disease, and 9.3% experienced a partial response. The median progression-free survival was 1.7 months, and the median overall survival was 6.8 months. CONCLUSIONS Gemcitabine alone did not show meaningful clinical benefit as second-line treatment after FOLFIRINOX.
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Asano T, Hirano S, Nakamura T, Okamura K, Tsuchikawa T, Noji T, Nakanishi Y, Tanaka K, Shichinohe T. Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2018; 25:342-350. [PMID: 29797499 DOI: 10.1002/jhbp.565] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Conversion surgery (CS) is expected as a new therapeutic strategy for patients with unresectable pancreatic cancer (UR-PC). We analyzed outcomes of CS for patients with UR-PC and evaluated the survival benefit of CS. METHODS Thirty-four patients diagnosed with UR-PC according to the National Comprehensive Cancer Network guideline underwent CS in our hospital. Resectability was considered by multimodal images in patients who underwent nonsurgical treatment (NST) for more than 6 months. CS was performed only in patients who were judged to be able to undergo R0 resection. RESULTS Twenty-six patients had locally advanced PC, and eight had distant metastases. The median duration of NST was 9 (range 5-44) months. R0 resection was achieved in 30 patients (88.2%). Six patients (17.6%) showed Evans grade ≥III. Three- and 5-year overall survival (OS) rates from initial treatment were 74% and 56.9%, respectively, with median survival time (MST) of 5.3 years. The actual 5-year OS rate in 19 patients was 47.4% with an MST of 4.0 years. Patients with Evans grade ≥III had a better prognosis than those with Evans grade <III (P = 0.0092, log-rank test). CONCLUSIONS Conversion surgery might have survival benefits to patients with UR-PC who responded favorably to NST.
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Affiliation(s)
- Toshimichi Asano
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Keisuke Okamura
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Yoshitsugu Nakanishi
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, West-7, North-15, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan
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21
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KOKKALI STEFANIA, TRIPODAKI ELLISOPHIA, DRIZOU MARIA, STEFANOU DIMITRA, MAGOU ELPIDA, ZYLIS DIMOSTHENIS, KAPIRIS MATTHAIOS, NASI DESPOINA, GEORGANTA CHARA, ARDAVANIS ALEXANDROS. Biweekly Gemcitabine/Nab-Paclitaxel as First-line Treatment for Advanced Pancreatic Cancer. In Vivo 2018; 32. [PMID: 29695574 PMCID: PMC6000799 DOI: 10.21873/invivo.112289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND/AIM During recent years, a survival advantage was reported for first-line treatment of advanced pancreatic cancer with two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel, over gemcitabine monotherapy. Gemcitabine/nab-paclitaxel administration on days 1, 8 and 15 of a 4-week cycle is associated with some practical disadvantages. We adopted a biweekly regimen with the same dose density. PATIENTS AND METHODS Patients with Eastern Cooperative Oncology Group performance status 0-2 diagnosed with advanced histologically or cytologically confirmed pancreatic cancer and no prior treatment were included in the study. Study combination included 1.5 g/m2 gemcitabine and 175 mg/m2 nab-paclitaxel given every 2 weeks. Survival analysis was performed using the Kaplan-Meier method. RESULTS Forty-six patients were treated with this regimen. Adverse events were similar to those of the original regimen. Median progression-free and overall survival were 5 and 10 months, respectively. CONCLUSION Biweekly gemcitabine/nab-paclitaxel seems to have a similar safety and efficacy profile as the original regimen.
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22
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Kokkali S, Tripodaki ES, Drizou M, Stefanou D, Magou E, Zylis D, Kapiris M, Nasi D, Georganta C, Ardavanis A. Biweekly Gemcitabine/Nab-Paclitaxel as First-line Treatment for Advanced Pancreatic Cancer. In Vivo 2018; 32:653-657. [PMID: 29695574 PMCID: PMC6000799 DOI: 10.21873/invivo.11289] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 02/13/2018] [Accepted: 02/20/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIM During recent years, a survival advantage was reported for first-line treatment of advanced pancreatic cancer with two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel, over gemcitabine monotherapy. Gemcitabine/nab-paclitaxel administration on days 1, 8 and 15 of a 4-week cycle is associated with some practical disadvantages. We adopted a biweekly regimen with the same dose density. PATIENTS AND METHODS Patients with Eastern Cooperative Oncology Group performance status 0-2 diagnosed with advanced histologically or cytologically confirmed pancreatic cancer and no prior treatment were included in the study. Study combination included 1.5 g/m2 gemcitabine and 175 mg/m2 nab-paclitaxel given every 2 weeks. Survival analysis was performed using the Kaplan-Meier method. RESULTS Forty-six patients were treated with this regimen. Adverse events were similar to those of the original regimen. Median progression-free and overall survival were 5 and 10 months, respectively. CONCLUSION Biweekly gemcitabine/nab-paclitaxel seems to have a similar safety and efficacy profile as the original regimen.
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Affiliation(s)
- Stefania Kokkali
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | | | - Maria Drizou
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Dimitra Stefanou
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Elpida Magou
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Dimosthenis Zylis
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Matthaios Kapiris
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Despoina Nasi
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
| | - Chara Georganta
- First Medical Oncology Clinic, Saint Savvas Anticancer Hospital, Athens, Greece
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23
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Zhang H, Kellett C, Lambert P, Kim CA. Efficacy and Tolerability of Second-line Nab-paclitaxel and Gemcitabine After Failure of First-line FOLFIRINOX for Advanced Pancreas Cancer: A Single-institution Experience. Clin Colorectal Cancer 2018; 17:e451-e456. [PMID: 29631907 DOI: 10.1016/j.clcc.2018.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Revised: 02/27/2018] [Accepted: 03/05/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Advanced pancreatic cancer (APC) has a poor prognosis. Current first-line chemotherapy options include FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin), NG (nab-paclitaxel, gemcitabine), and GEM (gemcitabine) alone. The optimal second-line regimen is unclear. For patients with disease progression with FOLFIRINOX who have a good performance status, NG might be a reasonable second-line option. PATIENTS AND METHODS Patients in whom APC was diagnosed from 2012 to 2016 who underwent chemotherapy at CancerCare Manitoba were identified from the Manitoba Cancer Registry. Pharmacy records were used to identified those patients who had received first-line FOLFIRINOX, followed by second-line NG, GEM alone, or best supportive care. A retrospective analysis was performed to identify the patient and treatment characteristics, toxicity, radiologic response, and survival. Edmonton Symptom Assessment System, revised, scores were analyzed to assess symptom control. RESULTS A total of 146 patients had received first-line FOLFIRINOX. Of those with disease progression who were offered second-line therapy, 30 received NG, 8 GEM alone, and 22 best supportive care. NG was more toxic than GEM alone; however, the dose intensity was similar between the 2 groups. The median progression-free survival was 3.61 months in the NG group and 2.51 months in the GEM-alone group. The median overall survival was 5.69 months in the NG group and 3.82 months in the GEM-alone group. No significant differences were found in the Edmonton Symptom Assessment System, revised, scores when stratified by the treatment received. CONCLUSION For select patients with APC in whom first-line FOLFIRINOX fails, a role might exist for second-line NG. In our institution, second-line NG was associated with improvement in survival compared with second-line GEM alone, with a manageable toxicity profile.
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Affiliation(s)
- Hanbo Zhang
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
| | | | | | - Christina A Kim
- Section of Haematology/Oncology, University of Manitoba, Winnipeg, MB, Canada
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Kang MJ, Jang JY, Kwon W, Kim SW. Clinical significance of defining borderline resectable pancreatic cancer. Pancreatology 2018; 18:139-145. [PMID: 29274720 DOI: 10.1016/j.pan.2017.12.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 11/21/2017] [Accepted: 12/06/2017] [Indexed: 12/11/2022]
Abstract
Since the introduction of the concept of borderline resectable pancreatic cancer (BRPC), various definitions of this disease entity have been suggested. However, there are several obstacles in defining this disease category. The current diagnostic criteria of BRPC mainly focuses on its expanded 'technical resectability'; however, they are difficult to interpret because of their ambiguity using potential subjective or arbitrary terminology, In addition, limitations in current imaging technology and a lack of evidence in radiological-pathological-clinical correlation make it difficult to refine the criteria. On the other hand, neoadjuvant treatment is usually applied to increase the R0 resection rate of BRPC focusing on the 'oncological curability'. However, evidence is needed concerning the effect of neoadjuvant treatment by quality-controlled prospective randomized clinical trials based on a standardized radiologic and pathologic reporting system. In conclusion, there are two aspects in the current concept of BRPC, which are technical resectability and oncological curability. Although the recent evolution of surgical techniques is expanding the scope of technical resectability, it should not be overlooked that the disease entity must be defined based on the evidence of oncological curability.
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Affiliation(s)
- Mee Joo Kang
- Korea International Cooperation Agency, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sun-Whe Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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25
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Palacio S, Hosein PJ, Reis I, Akunyili II, Ernani V, Pollack T, Macintyre J, Restrepo MH, Merchan JR, Rocha Lima CM. The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. J Gastrointest Oncol 2018; 9:135-139. [PMID: 29564179 DOI: 10.21037/jgo.2017.10.12] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The phase III MPACT trial for metastatic pancreatic cancer (PC) showed improved overall survival (OS), progression free survival (PFS) and response rates (RRs) for first-line nab-paclitaxel (Abraxane) and gemcitabine (the AG combination) compared to gemcitabine monotherapy. The safety and efficacy of the AG combination has not been systematically studied as second-line therapy or beyond for metastatic PC. We conducted an IRB-approved retrospective analysis of all patients diagnosed between September 2010 and August 2014 with advanced refractory PC that received combination treatment with AG at our institution. Demographic and survival data were extracted from the registry. Patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1,000 mg/m2 and on days 1, 8 and 15 of a 28-day cycle with subsequent dose modifications based on tolerance. Data on 59 patients was available; the median age was 61; 55% were male; 56% received AG as second line therapy and 44% received it as third-line or beyond. Five (10%) patients had a confirmed partial response (PR), 23 (47%) had stable disease (SD) and 21 (43%) had disease progression as their best response. Among the 31 (52%) patients who received prior gemcitabine, 18 (58%) had clinical benefit; 3 had a PR and 15 had SD. The median OS was 3.9 months and the median progression-free survival was 3 months. Toxicity was similar to what was reported in the MPACT trial. This retrospective analysis suggests that AG is active in PC patients previously treated with either fluoropyrimidine-based therapy or gemcitabine-based therapy with manageable toxicities.
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Affiliation(s)
- Sofia Palacio
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Peter J Hosein
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Isildinha Reis
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Ikechukwu I Akunyili
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Vinicius Ernani
- Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Terri Pollack
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Jessica Macintyre
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Maria H Restrepo
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Jaime R Merchan
- Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Caio M Rocha Lima
- Division of Oncology, Gibbs Comprehensive Cancer Center and Research Institute, Spartanburg, SC, USA
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Saung MT, Zheng L. Current Standards of Chemotherapy for Pancreatic Cancer. Clin Ther 2017; 39:2125-2134. [PMID: 28939405 DOI: 10.1016/j.clinthera.2017.08.015] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Revised: 08/23/2017] [Accepted: 08/24/2017] [Indexed: 12/18/2022]
Abstract
PURPOSE Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers patients meaningful benefit. METHODS This study reviewed the literature for recently published Phase III clinical trials whose results have guided the current standards of chemotherapy for pancreatic cancer. FINDINGS Although combination chemotherapy regimens are shown to be superior to gemcitabine monotherapy for both metastatic pancreatic cancer and adjuvant chemotherapy after surgical resection, it should be recognized that all combination chemotherapy regimens offer only limited benefits. In addition, there is a paucity of clinical trials that directly compare the various combination chemotherapy regimens. IMPLICATIONS With the advancement of systemic cancer treatment beyond chemotherapy, it is important to devote more investigation into better understanding the biology of these chemotherapy regimens, such that we combine them with targeted therapeutics and immunotherapeutics in a rational and scientific manner. For the current treatment of pancreatic cancer, the available chemotherapy regimens have shown modest but statistically significant improvements in survival. However, it is important to avoid cross-comparisons of trials and choose regimens based on patient characteristics and the side-effect profiles of the regimen.
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Affiliation(s)
- May Tun Saung
- The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Lei Zheng
- The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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