|
1
|
Efficacy and tolerance of cetuximab in combination with 5 FU plus irinotecan based chemotherapy in metastatic squamous cell anal carcinoma. Dig Liver Dis 2023; 55:407-411. [PMID: 36088220 DOI: 10.1016/j.dld.2022.08.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/13/2022] [Accepted: 08/17/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Squamous cell anal carcinoma (SCAC) is an uncommon neoplasia often cured by surgery and/or chemo-adiation therapy at the localized stage. Although the first-line treatment for metastatic anal canal cancer is now better codified with two validated treatment regimens, carboplatin-paclitaxel and modified docetaxel-cisplatin-5FU (DCF), there is little data and no consensus regarding subsequent lines [1-5]. In this study, we report the safety and efficacy of cetuximab (an epidermal growth factor receptor inhibitor) in combination with 5-FU plus irinotecan based chemotherapy. METHOD A retrospective analysis of patients with metastatic SCAC (mSCAC), who failed on at least one prior line of treatment, before being treated with the combination FOLFIRI and cetuximab between March 2015 and February 2022 at Gustave Roussy cancer center, was performed. RESULTS A total of 33 patients with a pre-treated mSCAC were analyzed. The combination of FOLFIRI and cetuximab provided a disease control rate (DCR) of 73%, and response rate of 30%. With a median follow-up of 38 months, the median progression free survival was 5.5 months, and the median overall survival was 13.7 months. Fourteen patients (42%) experienced grade III/IV adverse events that remained manageable. CONCLUSION Our study suggests that FOLFIRI and cetuximab is a promising combination in the management of mSCAC with a very good DCR and a manageable toxicity profile. Further prospective trials would be needed to confirm our results.
Collapse
|
|
2
|
Abstract
PURPOSE OF REVIEW We aim to summarise the available evidence on systemic therapies for advanced anal cancer. RECENT FINDINGS There is no universal consensus on the management of this condition and the prognosis remains poor. Nevertheless, significant progress has been recently made including completion of the first, ever-conducted, randomised trial in the first-line setting, investigation of immunotherapy in the refractory setting and use of comprehensive genomic profiling for a better molecular characterisation of this disease and the identification of novel potential targets. The combination of a platinum agent and a fluoropyrimidine is generally considered the standard first-line treatment. Other cytotoxic agents, especially docetaxel and paclitaxel, have shown activity in both the chemotherapy-naive and chemo-refractory setting and are currently being investigated in clinical trials. Finally, further to the promising results of early clinical trials, immunotherapy with checkpoint inhibitors (i.e. nivolumab and pembrolizumab) is likely to become a standard second-line treatment option.
Collapse
|
|
3
|
De Dosso S, Martin V, Zanellato E, Frattini M, Saletti P. Molecular Characterization and Response to Cetuximab in a Patient with Refractory Squamous Cell Anal Carcinoma. TUMORI JOURNAL 2018; 96:627-8. [DOI: 10.1177/030089161009600419] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
There are no standard chemotherapeutic options for patients with squamous cell anal carcinoma, relapsing and progressing on palliative cisplatin-based regimens. Similarly to other malignant conditions, monoclonal antibodies directed against the epidermal growth factor receptor may represent an attractive therapeutic strategy. Here we describe a patient who, based on molecular profile, benefited from the combination of irinotecan and cetuximab.
Collapse
Affiliation(s)
- Sara De Dosso
- Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Vittoria Martin
- Laboratory of Molecular Diagnostic, Istituto Cantonale di Patologia, Locarno, Switzerland
| | - Elena Zanellato
- Laboratory of Molecular Diagnostic, Istituto Cantonale di Patologia, Locarno, Switzerland
| | - Milo Frattini
- Laboratory of Molecular Diagnostic, Istituto Cantonale di Patologia, Locarno, Switzerland
| | - Piercarlo Saletti
- Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| |
Collapse
|
|
4
|
Koncar RF, Feldman R, Bahassi EM, Hashemi Sadraei N. Comparative molecular profiling of HPV-induced squamous cell carcinomas. Cancer Med 2017; 6:1673-1685. [PMID: 28556593 PMCID: PMC5504316 DOI: 10.1002/cam4.1108] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 03/29/2017] [Accepted: 04/30/2017] [Indexed: 12/21/2022] Open
Abstract
Approximately 5% of all cancer incidences result from human papillomavirus (HPV) infection. HPV infection most commonly leads to cancers of the anogenital region or oropharynx. It is unknown whether different HPV-mediated cancers collectively share a molecular signature and it is important to determine if there are targetable alterations common to different types of HPV-positive tumors. We analyzed 743 p53 wild-type samples of anal, cervical, oropharyngeal, and vulvar squamous cell carcinomas which underwent multiplatform testing at a commercial molecular profiling service. Expression of 24 proteins was measured by immunohistochemistry (IHC), mutation of 48 genes was determined by next-generation and Sanger sequencing, and copy number alteration for six genes was determined by in situ hybridization. The four cohorts had remarkably similar molecular profiles. No gene had a statistically significant difference in mutation frequency or copy number change between the four different types of squamous cell carcinomas. The only significant differences between cohorts were frequency of ERCC1 and SPARC loss as determined by IHC. In all four cancer types, oncogene mutation and PD-L1 expression was relatively infrequent. The most commonly mutated gene was PIK3CA, with mutations most often affecting the helical domain of the protein and accompanied by concurrent lack of PTEN expression. Loss of MGMT and RRM1 was common among the four cohorts and may be predictive of response to cytotoxic therapies not currently being used to treat these cancer types. The similar molecular profiles of the four cohorts indicate that treatment strategies may be similarly efficacious across HPV-positive cancers.
Collapse
Affiliation(s)
- Robert F Koncar
- Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio
| | | | - El Mustapha Bahassi
- Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio
| | - Nooshin Hashemi Sadraei
- Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio
| |
Collapse
|
|
5
|
|
|
6
|
Houlihan OA, O'Neill BD. Chemoradiotherapy for anal squamous cell carcinoma. Surgeon 2016; 14:202-12. [DOI: 10.1016/j.surge.2016.03.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 03/10/2016] [Accepted: 03/18/2016] [Indexed: 01/27/2023]
|
|
7
|
Smaglo BG, Tesfaye A, Halfdanarson TR, Meyer JE, Wang J, Gatalica Z, Reddy S, Arguello D, Boland PM. Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas. Oncotarget 2015; 6:43594-604. [PMID: 26498363 PMCID: PMC4791253 DOI: 10.18632/oncotarget.6202] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 10/09/2015] [Indexed: 02/01/2023] Open
Abstract
Anal squamous cell carcinoma (ASCC) is a rare, HPV-associated malignancy typically diagnosed in early stages and definitively treated with chemoradiation. In situations where patients exhibit metastatic or recurrent disease, treatment options are severely limited. In this study, molecular alterations were identified that could be used to aid in therapeutic decisions for patients with metastatic or recurrent anal squamous cell carcinoma. Specimens from patients with this cancer were tested via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing, protein expression by immunohistochemistry, and gene amplification with in situ hybridization. Utilizing these techniques, novel treatment strategies that could be explored were identified, including potential benefit with anti-EGFR therapies, immune checkpoint inhibitors, topoisomerase inhibitors, and taxanes. The frequency of overexpression of proteins that mark resistance to chemotherapeutic drugs, such as MRP1 (chemotherapy efflux pump), ERCC1 (resistance to platinum-based chemotherapy), and thymidylate synthase (resistance to fluoropyrimidines) were also identified, suggesting a lack of benefit. This multiplatform strategy could be explored for its potential to generate a personalized treatment selection for patients with advanced ASCC, provide a guide for future therapeutic development for this cancer, and be extended to other rare cancer types as well.
Collapse
Affiliation(s)
- Brandon G. Smaglo
- The Ruesch Center for the Cure of GI Cancers, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA
| | - Anteneh Tesfaye
- Departments of Hematology/Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA
| | | | - Joshua E. Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Jue Wang
- Division of Oncology, University of Arizona Cancer Center, Phoenix, AZ, USA
| | - Zoran Gatalica
- Department of Pathology, Caris Life Sciences, Phoenix, AZ, USA
| | - Sandeep Reddy
- Department of Pathology, Caris Life Sciences, Phoenix, AZ, USA
| | - David Arguello
- Department of Pathology, Caris Life Sciences, Phoenix, AZ, USA
| | - Patrick M. Boland
- Department of Medicine, GI Center, Roswell Park Cancer Institute, Buffalo, NY, USA
| |
Collapse
|
|
8
|
Bustamante L, Frakes J, Hoffe S, Kim R. Investigational drugs for treating anal cancer and future perspectives. Expert Opin Investig Drugs 2015; 25:51-62. [PMID: 26560877 DOI: 10.1517/13543784.2016.1116518] [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: 11/05/2022]
Abstract
INTRODUCTION Anal cancer is a relatively rare malignancy which comprises about 2.5% of all digestive system malignancies in the United States. The majority of cases are squamous cell carcinoma which is closely related to human papilloma virus (HPV) infection. Despite high cure rates with chemoradiation alone, 10 - 20% of patients do develop metastatic disease with little data to guide their treatment. AREAS COVERED In this review article, the authors describe the current standard treatment of early and advanced squamous cell carcinoma of the anal canal based on published data. The authors then describe the new approaches to the disease, focusing on new radio sensitizing agents, systemic targeted drugs and immunotherapy. EXPERT OPINION The authors believe that current standard treatment options for squamous cell carcinoma of the anal canal are well defined with acceptable results. However the major challenge in the treatment of anal cancer is the lack of randomized or even large single arm Phase II trials due to rarity of the disease, especially in the metastatic disease. But we are slowly making progress. Currently, the most promising areas of research are immunotherapy, targeted therapy and even HPV prevention. We are eagerly anticipating the results of these studies in order to expand the treatment armamentarium.
Collapse
Affiliation(s)
- Liliana Bustamante
- a Department of Gastrointestinal Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , FL 33612 , USA
| | - Jessica Frakes
- b Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , FL 33612 , USA
| | - Sarah Hoffe
- b Department of Radiation Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , FL 33612 , USA
| | - Richard Kim
- a Department of Gastrointestinal Oncology , H. Lee Moffitt Cancer Center and Research Institute , Tampa , FL 33612 , USA
| |
Collapse
|
|
9
|
Yellu M, Deeb A, Olowokure O. Overview of Recent Trends in the Management of Metastatic Anal Cancer. World J Oncol 2015; 6:311-315. [PMID: 29147423 PMCID: PMC5649953 DOI: 10.14740/wjon866w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2014] [Indexed: 01/22/2023] Open
Abstract
Anal cancer is a relatively rare gastrointestinal tumor with roughly 7,000 new cases per year. Metastatic anal cancer as an initial presentation occurs in 10-20% of the patients. Treatment for localized disease is well established with concurrent chemoradiation (CCR) therapy as the standard of care; however, metastatic anal cancer remains a therapeutic challenge. National Comprehensive Cancer Network (NCCN) guidelines recommend systemic chemotherapy as the initial choice of treatment for metastatic anal disease. NCCN also recognizes the fact that there are limited data to influence the management of metastatic anal cancer but that some evidence suggests flouropyrimidine and cisplatin as the initial choice of treatment outside the setting of clinical trial. If the patient fails this regimen, options become limited with no strong level I evidence available to guide the treatment. We present two cases of metastatic anal cancer and discuss the potential treatment strategies after failing the initial systemic chemotherapy.
Collapse
Affiliation(s)
- Mahender Yellu
- Division of Hematology/Oncology, Stem Cell Transplantation, University of Cincinnati, Cincinnati, OH 45229, USA
| | - Ayham Deeb
- Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH 45229, USA
| | - Olugbenga Olowokure
- Division of Hematology/Oncology, University of Cincinnati, Cincinnati, OH 45229, USA
| |
Collapse
|
|
10
|
Funahashi K, Nemoto T, Koike J, Kurihara A, Shiokawa H, Ushigome M, Kaneko T, Arai K, Nagashima Y, Koda T, Suzuki T, Kagami S, Suitsu Y, Kaneko H, Shibuya T. Chemoradiation therapy with S-1 for primary squamous cell carcinoma of the rectum: report of three cases. Surg Case Rep 2015; 1:14. [PMID: 26943382 PMCID: PMC4747969 DOI: 10.1186/s40792-015-0025-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 01/27/2015] [Indexed: 12/24/2022] Open
Abstract
Purpose Although successful treatment of squamous cell carcinoma (SCC) of the rectum using chemoradiation therapy (CRT) has been reported, a standard protocol has yet to be established. The aim is to ascertain the effectiveness of CRT with S-1 for three patients with SCC of the rectum. Case presentation We treated three female patients complaining of rectal bleeding. The patients were diagnosed as having primary SCC of the rectum by means of routine examinations; one of them was a very rare case because of the presence of two lesions in the lower rectum. We treated the patients using CRT with S1 at a radiation dose of 1.8 Gy/fraction given five times weekly (Monday to Friday) to a median dose of 59.4 (45 to 59.4) Gy; S-1 (80 mg/m2/day) was administered orally during radiation therapy. One of three patients had an adverse event involving massive hemorrhage from the tumor. All patients exhibited an excellent response to CRT with S-1; two patients had a complete response, and one patient had a partial response and underwent a posterior pelvic exenteration with advancement flap reconstruction as a salvage treatment. Pathological examination of the resected specimen and lymph nodes revealed no tumor cells indicating a pathological complete response. In this series, the response rate was 100%. Conclusions We suggest that CRT with S-1 be chosen as the first-line therapy for SCC of the rectum. However, a large study will be required to establish a safe and effective regimen.
Collapse
Affiliation(s)
- Kimihiko Funahashi
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Tetsuo Nemoto
- Department of Pathology, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Junichi Koike
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Akiharu Kurihara
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Hiroyuki Shiokawa
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Mistunori Ushigome
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Tomoaki Kaneko
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Kenichiro Arai
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Yasuo Nagashima
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Takamaru Koda
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Takayuki Suzuki
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Satoru Kagami
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Yu Suitsu
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Hironori Kaneko
- Department of General and Gastroenterological Surgery, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| | - Toshikazu Shibuya
- Department of Pathology, Toho University Medical Center, Omori Hospital, 6-11-1 Omorinishi, Otaku, Tokyo, 143-8541, Japan.
| |
Collapse
|
|
11
|
Squamous Cell Carcinoma of the Anal Canal. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
12
|
|
|
13
|
Cetuximab in Refractory Squamous Cell Carcinoma of the Anal Canal. J Gastrointest Cancer 2014; 45 Suppl 1:198-200. [DOI: 10.1007/s12029-014-9626-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
14
|
Khawandanah M, Baxley A, Pant S. Recurrent metastatic anal cancer treated with modified paclitaxel, ifosfamide, and cisplatin and third-line mitomycin/cetuximab. J Oncol Pharm Pract 2014; 21:232-7. [PMID: 24627343 DOI: 10.1177/1078155214526268] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE Squamous cell carcinoma represents approximately 75% of all anal cancers. Squamous cell carcinoma of the anal canal is a rare malignancy often curable in the early stages with the combined modality therapy of chemoradiation. Treatment in the metastatic setting is challenging due to the rarity of metastatic disease with the majority of patients presenting with curative locally advanced disease, and the ability to design clinical trials for metastatic disease has yet to be explored. There are no established chemotherapy guidelines for patients with metastatic anal cancer after the failure of cisplatin and fluorouracil. METHODS We used PubMed and OVID research engines to identify publications in English literature addressing treatments/therapeutics using the following keywords "metastatic anal cancer" and "metastatic squamous cell carcinoma of anus" in addition to reviewing related clinical trials in clinicaltrials.gov. RESULTS We hereby report our experience in using aggressive combinations in the second- and third-line settings. A 49-year-old white male diagnosed with T3 N3 M0 Stage IIIB anal cancer was treated initially with surgical excision and adjuvant fluorouracil/cisplatin due unavailability of mitomycin. He developed metastatic disease to the skin and perianal region, was treated with four cycles of paclitaxel, ifosfamide, and cisplatin with growth factor support, and achieved minimal residual disease. On progression five months after finishing therapy, we treated him with mitomycin and cetuximab with mixed response after two cycles. The patient later elected to proceed with hospice care only and succumbed to his disease 16 months after first cycle of paclitaxel, ifosfamide, and cisplatin and 24 months from diagnosis. CONCLUSIONS Paclitaxel, ifosfamide, and cisplatin is highly active in metastatic setting in selected patients. Cetuximab based regimen can be valuable option as second or third line. Paclitaxel, ifosfamide, and cisplatin and mitomycin and cetuximab can be available options for unmet need in metastatic anal cancer.
Collapse
Affiliation(s)
- Mohamad Khawandanah
- Section of Hematology-Oncology, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Allison Baxley
- Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Shubham Pant
- Section of Hematology-Oncology, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| |
Collapse
|
|
15
|
Abstract
Due to the low incidence of anal cancer and generally high cure rates, few second-line treatment options have been evaluated in the setting of formal clinical trials. We briefly report two cases that were both found to have wild-type K-RAS, with no epidermal growth factor receptor amplification or evidence of prior persistent human papilloma virus infection. Both cases were treated with irinotecan and cetuximab with evidence of clinical benefit in the setting of a third recurrence, as well as evidence of response to other strategies employed in their management. These cases provide support for the suggestion that treatment planning in conjunction with molecular profiling may be beneficial in such uncommon clinical settings.
Collapse
Affiliation(s)
- Eiko Klimant
- Eastern Regional Medical Center, Cancer Treatment Centers of America, Philadelphia, Pa., USA
| | | |
Collapse
|
|
16
|
|
|
17
|
Cacheux W, Lievre A, De La Rochefordiere A, Dieumegard B, Cvitkovic F, Labib A, Mitry E, Buecher B. Chemotherapy in the treatment of anal canal carcinoma. Dig Liver Dis 2012; 44:803-11. [PMID: 22658644 DOI: 10.1016/j.dld.2012.04.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 04/18/2012] [Indexed: 12/11/2022]
Abstract
Squamous cell carcinomas of the anal canal are generally diagnosed at a localized or locally advanced stage and only 5% are metastatic at the time of diagnosis. Advanced forms are therefore much rarer than localized forms and usually correspond to metachronous metastases of initially localized disease. Systemic chemotherapy is indicated for the treatment of both localized disease, in combination with radiotherapy, and metastatic disease. The purpose of this article is to define the current indications and modalities of chemotherapy in the treatment of these cancers based on a review of the published data and in the light of available guidelines.
Collapse
Affiliation(s)
- Wulfran Cacheux
- Department of Medical Oncology, Groupe Hospitalier, Institut Curie, 26 rue d'Ulm, 75248 Paris Cédex 5, France
| | | | | | | | | | | | | | | |
Collapse
|
|
18
|
|
|
19
|
Oliveira S, Teixeira L, Hoff PM, de Gramont A, Tournigand C. Squamous-cell carcinoma of the anal canal: room for improvement with targeted therapy. Clin Res Hepatol Gastroenterol 2012; 36:209-13. [PMID: 22138064 DOI: 10.1016/j.clinre.2011.10.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 10/25/2011] [Accepted: 10/27/2011] [Indexed: 02/04/2023]
Abstract
Carcinoma of the anal canal is a rare disease accounting for 1-5% of gastrointestinal tract malignancies. However, its incidence is increasing worldwide. Chemoradiation is the standard treatment for most patients with squamous-cell carcinoma of the anal canal and was first described by Nigro et al. Since then, no other effective treatment was developed. Patients with metastatic disease should be considered candidates for clinical trials. New treatment strategies, including molecular target therapies, are warranted in order to improve disease control. Despite the rarity of this disease, it is urgent to improve its treatment by introducing targeted therapy in the arena.
Collapse
Affiliation(s)
- Suilane Oliveira
- Instituto do Cancer do Estado de São Paulo, 251 avenida Doutor Arnaldo, 01246-000 São Paulo, Brazil.
| | | | | | | | | |
Collapse
|
|
20
|
Dewdney A, Rao S. Metastatic squamous cell carcinoma of the anus: time for a shift in the treatment paradigm? ISRN ONCOLOGY 2012; 2012:756591. [PMID: 22619735 PMCID: PMC3352602 DOI: 10.5402/2012/756591] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/10/2012] [Accepted: 01/29/2012] [Indexed: 02/06/2023]
Abstract
Anal cancers are rare tumours; however, the incidence is increasing in both men and women. Changing trends in sexual behaviour, smoking, and infection with the human papillomavirus are thought to be responsible for the increase. Patients with metastatic disease have a poor prognosis, with 5-year median overall survival rates of 10% in men and 20% in women. The standard systemic treatment of metastatic disease remains cisplatin and 5-fluorouracil, and aside from several non-randomised small phase II trials there has been no real progress over the past two decades. Based on the efficacy of cetuximab in squamous cell carcinomas from other primary sites, there appears to be clinical rationale for evaluation of anti-epidermal growth factor inhibitors in anal squamous cell carcinoma. In order to facilitate research and implement more effective treatment strategies international collaboration in clinical trials incorporating tissue collection for biomarkers is essential.
Collapse
Affiliation(s)
- Alice Dewdney
- Department of Medicine, Royal Marsden Hospital, London and Surrey, UK
| | | |
Collapse
|
|
21
|
Lim F, Glynne-Jones R. Chemotherapy/chemoradiation in anal cancer: A systematic review. Cancer Treat Rev 2011; 37:520-32. [DOI: 10.1016/j.ctrv.2011.02.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2010] [Revised: 02/07/2011] [Accepted: 02/27/2011] [Indexed: 12/27/2022]
|
|
22
|
A regimen of taxol, Ifosfamide, and platinum for recurrent advanced squamous cell cancer of the anal canal. CHEMOTHERAPY RESEARCH AND PRACTICE 2011; 2011:163736. [PMID: 22295202 PMCID: PMC3265251 DOI: 10.1155/2011/163736] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2011] [Accepted: 04/18/2011] [Indexed: 12/12/2022]
Abstract
The typically recommended chemotherapy options in metastatic anal cancer generally yield partial remissions with limited benefit for the majority of patients. TIP is a regimen containing paclitaxel (Taxol), ifosfamide, and cisplatin that is known to have significant activity in patients with squamous cell cancers of the head and neck as well as in cervical cancer, both of which are malignancies strongly associated with oncogenic strains of human papilloma virus (HPV). Interestingly, squamous cell cancer of the anal canal shares an almost identical pathophysiology including causal association with HPV. Due to this, we chose to use the TIP regimen to treat patients with advanced anal cancer at our institution and report our findings on three such consecutive patients. All the patients tolerated the regimen well with manageable side effects and had excellent responses with complete resolution of PET activity after treatment. Our observations suggest that TIP is highly active for squamous cell cancer of the anal canal and warrants further study in the treatment of this disease.
Collapse
|
|
23
|
The Role of EGFR Inhibitors in the Treatment of Metastatic Anal Canal Carcinoma: A Case Series. JOURNAL OF ONCOLOGY 2011; 2011:125467. [PMID: 21772841 PMCID: PMC3136097 DOI: 10.1155/2011/125467] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Revised: 04/14/2011] [Accepted: 04/15/2011] [Indexed: 11/17/2022]
Abstract
Anal cancer patients who have exhibited disease progression after having received all approved drugs pose a major therapeutic challenge. In addition to cytotoxic agents, novel targeted agents are being developed and have an established role in the treatment of many solid tumors, including colon cancer. However, their role in anal cancer is yet to be determined. Most anal malignancies are squamous cell carcinomas often strongly expressing epidermal growth factor receptors (EGFRs). Targeting the latter seems to result in favorable changes in tumor growth. We present three cases of refractory anal cancers, treated with EGFR inhibitors, after having received the recommended chemotherapy regimens. We conclude that EGFR inhibitors may play a vital role in the treatment of anal cancer and we suggest that large trials are be conducted in order to clarify their efficacy and to improve therapeutic management.
Collapse
|
|
24
|
Combined-Modality Treatment for Anal Cancer. Strahlenther Onkol 2010; 186:361-6. [DOI: 10.1007/s00066-010-2162-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2010] [Accepted: 04/27/2010] [Indexed: 11/25/2022]
|
|
25
|
|
|
26
|
Zampino MG, Magni E, Sonzogni A, Renne G. K-ras status in squamous cell anal carcinoma (SCC): it's time for target-oriented treatment? Cancer Chemother Pharmacol 2009; 65:197-9. [PMID: 19727729 DOI: 10.1007/s00280-009-1117-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2009] [Accepted: 08/17/2009] [Indexed: 12/22/2022]
Abstract
PURPOSE Squamous cell anal carcinoma (SCC) is an uncommon disease comprising only 1-5% of all intestinal tumours. SCC is now considered the prototype for the successful application of conservative treatment as chemoradiation instead of aggressive surgery. The EGFR status and k-ras mutations in SCC of the anal canal has not been well investigated. The purpose of our evaluation was to give information about this issue. METHODS From June 1999 to December 2008, 32 patients affected by SCC were treated in our institution with chemotherapy containing Fluoropyrimidine and platinum salt concomitant with pelvic radiotherapy. Immunohistochemistry for EGFR and k-ras mutation was retrospectively evaluated. RESULTS Twenty-six specimens were considered evaluable for biological objectives: K-ras mutation was performed in all cases, while EGFR in 12. In all cases of our series wild-type K-ras was observed. CONCLUSIONS Such information is, in our knowledge, the Wrst reported in literature on this setting. This observation previously reported in other tumours has supported the effective use of EGFR-inhibitors in recurrent or metastatic disease. This observation could support the role of EGFR-inhibitors in the treatment of SCC.
Collapse
Affiliation(s)
- Maria Giulia Zampino
- Medical Care Unit, Department of Medicine, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
| | | | | | | |
Collapse
|
|
27
|
Treatment Options in Metastatic Squamous Cell Carcinoma of the Anal Canal. Curr Treat Options Oncol 2009; 9:400-7. [DOI: 10.1007/s11864-009-0103-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2008] [Accepted: 04/20/2009] [Indexed: 11/29/2022]
|
|
28
|
Maingon P, Créhange G, Peignaux K, Truc G. Place potentielle des thérapies ciblées en association avec la radiothérapie dans les cancers digestifs. Cancer Radiother 2008; 12:25-30. [DOI: 10.1016/j.canrad.2007.11.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2007] [Revised: 11/20/2007] [Accepted: 11/23/2007] [Indexed: 10/22/2022]
|
|
29
|
Tetzlaff E, Polansky M, Carr K, Mares J, Vu L. Physician assistants in oncology. J Oncol Pract 2007; 3:283. [PMID: 20859427 DOI: 10.1200/jop.0759001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Eric Tetzlaff
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
| | | | | | | | | |
Collapse
|