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1
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Fortunato AR, Barbosa C, Araujo A, Fernandez-Llimos F. Influence of the estimated glomerular filtration rate equation on carboplatin dosing: a real-world study. Front Pharmacol 2025; 16:1605458. [PMID: 40567373 PMCID: PMC12187738 DOI: 10.3389/fphar.2025.1605458] [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: 04/03/2025] [Accepted: 05/30/2025] [Indexed: 06/28/2025] Open
Abstract
Background Carboplatin is a renally excreted antineoplastic drug associated with myelotoxic effects. Doses are calculated according to the Calvert formula. The change from Cockcroft-Gault (CG) to the race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) may have an impact on doses. The aim of the study was to evaluate the difference in carboplatin doses based on estimated glomerular filtration rate (eGFR) calculated using the two different equations (i.e., CG and CKD-EPI) applied to a real-world dataset of carboplatin administrations. Materials and methods Retrospective study simulating the effect of switching to CKD-EPI on doses calculated using CG. Real-world data were collected on all carboplatin doses administered in a general hospital oncology day-care unit during 2023. Doses originally calculated using CG estimates were recalculated using CKD-EPI results. A Bland-Altman analysis was performed to assess the discrepancies between the two equations. Correlations with anthropometric data were examined. Result A total of 487 cycles were administered to 126 patients with a mean age of 58.3 years (SD 12.6), 60.3% were female. There was a significant mean difference (p < 0.001) with a moderate effect (Cohen's d = 0.474) between clearance calculated with CG and eGFR calculated with CKD-EPI. CKD-EPI calculated doses had a mean 52 mg higher (limits of agreement -107 + 211). Percentage differences between CKD-EPI and CG doses ranged from +70.9% (CG = 405 mg, CKD-EPI = 692 mg) to -24.3% (CG = 684 mg, CKD-EPI = 518 mg). Differences were strongly correlated with body mass index (BMI) (p < 0.001, R = 0.681). Conclusion Clinically relevant differences were found between carboplatin doses calculated with CG and CKD-EPI. These differences were more relevant in male patients with low BMI.
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Affiliation(s)
| | - Cátia Barbosa
- Pharmacy Department, ULS Alto Ave, Guimarães, Portugal
| | - Ariana Araujo
- Pharmacy Department, ULS Alto Ave, Guimarães, Portugal
| | - Fernando Fernandez-Llimos
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
- Applied Molecular Biosciences Unit (UCIBIO), Faculty of Pharmacy, University of Porto, Porto, Portugal
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2
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Kicken MP, Deenen MJ, van der Wekken AJ, van den Borne BEEM, van den Heuvel MM, Ter Heine R. Opportunities for Precision Dosing of Cytotoxic Drugs in Non-Small Cell Lung Cancer: Bridging the Gap in Precision Medicine. Clin Pharmacokinet 2025; 64:511-531. [PMID: 40045151 PMCID: PMC12041064 DOI: 10.1007/s40262-025-01492-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2025] [Indexed: 04/30/2025]
Abstract
Precision dosing of classical cytotoxic drugs in oncology remains underdeveloped, especially in treating non-small cell lung cancer (NSCLC). Despite advancements in targeted therapy and immunotherapy, classical cytotoxic agents continue to play a critical role in NSCLC treatment. However, the current body surface area (BSA)-based dosing of these agents fails to adequately address interindividual variability in pharmacokinetics. By better considering patient characteristics, treatment outcomes can be improved, reducing risks of under-exposure and over-exposure. This narrative review explores opportunities for precision dosing for key cytotoxic agents used in NSCLC treatment: cisplatin, carboplatin, pemetrexed, docetaxel, (nab-)paclitaxel, gemcitabine, and vinorelbine. A comprehensive review of regulatory reports and an extensive literature search were conducted to evaluate current dosing practices, pharmacokinetics, pharmacodynamics, and exposure-response relationships. Our findings highlight promising developments in precision dosing, although the number of directly implementable strategies remains limited. The most compelling evidence supports using the biomarker cystatin C for more precise carboplatin dosing and adopting weekly dosing schedules for docetaxel, paclitaxel, and nab-paclitaxel. Additionally, we recommend direct implementation of therapeutic drug monitoring (TDM)-guided dosing for paclitaxel. This review stresses the urgent need to reassess conventional dosing paradigms for classical cytotoxic agents to better align with the principles of the precision dosing framework. Our recommendations show the potential of precision dosing to improve NSCLC treatment, addressing gaps in the current dosing of classical cytotoxic drugs. Given the large NSCLC patient population, optimising the dosing of these agents could significantly improve treatment outcomes and reduce toxicity for many patients.
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Affiliation(s)
- M P Kicken
- Department of Clinical Pharmacy, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.
- Department of Pharmacy, Radboudumc, Research Institute for Medical Innovation, Nijmegen, The Netherlands.
| | - M J Deenen
- Department of Clinical Pharmacy, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, The Netherlands
| | - A J van der Wekken
- Department of Pulmonology and Tuberculosis, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | | | - M M van den Heuvel
- Department of Pulmonology, Radboudumc, Research Institute for Medical Innovation, Nijmegen, The Netherlands
- Department of Pulmonology, University Medical Center, Utrecht, The Netherlands
| | - R Ter Heine
- Department of Pharmacy, Radboudumc, Research Institute for Medical Innovation, Nijmegen, The Netherlands
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3
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Pusta A, Tertis M, Ardusadan C, Mirel S, Cristea C. Electrochemical Sensing Device for Carboplatin Monitoring in Proof-of-Concept Drug Delivery Nanosystems. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:793. [PMID: 38727386 PMCID: PMC11085464 DOI: 10.3390/nano14090793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/19/2024] [Accepted: 04/30/2024] [Indexed: 05/12/2024]
Abstract
(1) Background: Carboplatin (CBP) is a chemotherapeutic drug widely used in the treatment of a variety of cancers. Despite its efficiency, CBP is associated with side effects that greatly limit its clinical use. To mitigate these effects, CBP can be encapsulated in targeted delivery systems, such as liposomes. Ensuring the adequate loading and release of CBP from these carriers requires strict control in pharmaceutical formulation development, demanding modern, rapid, and robust analytical methods. The aim of this study was the development of a sensor for the fast and accurate quantification of CBP and its application on proof-of-concept CBP-loaded nanosomes. (2) Methods: Screen-printed electrodes were obtained in-lab and the electrochemical behavior of CBP was tested on the obtained electrodes. (3) Results: The in-lab screen-printed electrodes demonstrated superior properties compared to commercial ones. The novel sensors demonstrated accurate detection of CBP on a dynamic range from 5 to 500 μg/mL (13.5-1350 μM). The method was successfully applied on CBP loaded and released from nanosomes, with strong correlations with a spectrophotometric method used as control. (4) Conclusions: This study demonstrates the viability of electrochemical techniques as alternative options during the initial phases of pharmaceutical formulation development.
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Affiliation(s)
- Alexandra Pusta
- Department of Analytical Chemistry, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (A.P.); (C.A.); (C.C.)
- Department of Medical Devices, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Mihaela Tertis
- Department of Analytical Chemistry, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (A.P.); (C.A.); (C.C.)
| | - Catalina Ardusadan
- Department of Analytical Chemistry, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (A.P.); (C.A.); (C.C.)
| | - Simona Mirel
- Department of Medical Devices, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Cecilia Cristea
- Department of Analytical Chemistry, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (A.P.); (C.A.); (C.C.)
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4
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Porfyriou E, Letsa S, Kosmas C. Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors. World J Clin Oncol 2021; 12:746-766. [PMID: 34631440 PMCID: PMC8479351 DOI: 10.5306/wjco.v12.i9.746] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/19/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors (GCTs) who failed to be cured by conventional chemotherapy. Hematopoietic stem cells (HSCs) collected from the peripheral blood, after appropriate pharmacologic mobilization, have largely replaced bone marrow as the principal source of HSCs in transplants. As it is currently common practice to perform tandem or multiple sequential cycles of HDCT, it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure. Moreover, the CD34+ cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment, with patients who receive > 2 × 106 CD34+ cells/kg having consistent, rapid, and sustained hematopoietic recovery. However, many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy, which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy. Therefore, alternative strategies that use novel agents in combination with traditional mobilizing regimens are required. Herein, after an overview of the mechanisms of HSCs mobilization, we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs, and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.
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Affiliation(s)
- Eleni Porfyriou
- Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
| | - Sylvia Letsa
- Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
| | - Christos Kosmas
- Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
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5
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Le Louedec F, Puisset F, Thomas F, Chatelut É, White-Koning M. Easy and reliable maximum a posteriori Bayesian estimation of pharmacokinetic parameters with the open-source R package mapbayr. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY 2021; 10:1208-1220. [PMID: 34342170 PMCID: PMC8520754 DOI: 10.1002/psp4.12689] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/22/2021] [Accepted: 06/28/2021] [Indexed: 12/28/2022]
Abstract
Pharmacokinetic (PK) parameter estimation is a critical and complex step in the model‐informed precision dosing (MIPD) approach. The mapbayr package was developed to perform maximum a posteriori Bayesian estimation (MAP‐BE) in R from any population PK model coded in mrgsolve. The performances of mapbayr were assessed using two approaches. First, “test” models with different features were coded, for example, first‐order and zero‐order absorption, lag time, time‐varying covariates, Michaelis–Menten elimination, combined and exponential residual error, parent drug and metabolite, and small or large inter‐individual variability (IIV). A total of 4000 PK profiles (combining single/multiple dosing and rich/sparse sampling) were simulated from each test model, and MAP‐BE of parameters was performed in both mapbayr and NONMEM. Second, a similar procedure was conducted with seven “real” previously published models to compare mapbayr and NONMEM on a PK outcome used in MIPD. For the test models, 98% of mapbayr estimations were identical to those given by NONMEM. Some discordances could be observed when dose‐related parameters were estimated or when models with large IIV were used. The exploration of objective function values suggested that mapbayr might outdo NONMEM in specific cases. For the real models, a concordance close to 100% on PK outcomes was observed. The mapbayr package provides a reliable solution to perform MAP‐BE of PK parameters in R. It also includes functions dedicated to data formatting and reporting and enables the creation of standalone Shiny web applications dedicated to MIPD, whatever the model or the clinical protocol and without additional software other than R.
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Affiliation(s)
- Félicien Le Louedec
- Inserm UMR1037, Cancer Research Center of Toulouse, Toulouse, France.,Faculty of Pharmacy, Université Paul Sabatier Toulouse III, Toulouse, France.,Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Florent Puisset
- Inserm UMR1037, Cancer Research Center of Toulouse, Toulouse, France.,Faculty of Pharmacy, Université Paul Sabatier Toulouse III, Toulouse, France.,Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Fabienne Thomas
- Inserm UMR1037, Cancer Research Center of Toulouse, Toulouse, France.,Faculty of Pharmacy, Université Paul Sabatier Toulouse III, Toulouse, France.,Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Étienne Chatelut
- Inserm UMR1037, Cancer Research Center of Toulouse, Toulouse, France.,Faculty of Pharmacy, Université Paul Sabatier Toulouse III, Toulouse, France.,Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Mélanie White-Koning
- Inserm UMR1037, Cancer Research Center of Toulouse, Toulouse, France.,Faculty of Pharmacy, Université Paul Sabatier Toulouse III, Toulouse, France
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6
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Chevreau C, Massard C, Flechon A, Delva R, Gravis G, Lotz JP, Bay JO, Gross-Goupil M, Fizazi K, Mourey L, Paci A, Guitton J, Thomas F, Lelièvre B, Ciccolini J, Moeung S, Gallois Y, Olivier P, Culine S, Filleron T, Chatelut E. Multicentric phase II trial of TI-CE high-dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors. Cancer Med 2021; 10:2250-2258. [PMID: 33675184 PMCID: PMC7982623 DOI: 10.1002/cam4.3687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 09/28/2020] [Accepted: 11/07/2020] [Indexed: 12/02/2022] Open
Abstract
Background High‐dose chemotherapy (HDCT) with TI‐CE regimen is a valid option for the treatment of relapsed advanced germ cell tumors (GCT). We report a phase II trial with therapeutic drug monitoring of carboplatin for optimizing area under the curve (AUC) of this drug. Methods Patients with unfavorable relapsed GCT were treated according to TI‐CE regimen: two cycles combining paclitaxel and ifosfamide followed by three cycles of HD carboplatin plus etoposide administered on 3 days. Carboplatin dose was adapted on day 3 based on carboplatin clearance (CL) at day 1 in order to reach a target AUC of 24 mg.min/mL per cycle. The primary endpoint was the complete response (CR) rate. Results Eighty‐nine patients who received HDCT were included in the modified intent‐to‐treat (mITT) analysis. Measured mean AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 mg.min/mL for 10th and 90th percentiles). Thirty‐five (44.3%) patients achieved a CR with or without surgery of residual masses and 20 patients achieved a partial response with negative tumor markers. With a median follow‐up of 44 months (m), median PFS was 12.3 m (95% CI: 7.5–25.9) and OS was 46.3 m (95% CI: 18.6–not reached). For high‐ and very high‐risk patients, according to the International Prognostic Score at first relapse or treated after at least one salvage treatment (n = 51), 2‐year PFS rate was 41.1%. Conclusion The rates of complete and favorable responses were clinically relevant in this very poor risk population. Individual monitoring of carboplatin plasma concentration permitted to control more accurately the target AUC and avoided both underexposure and overexposure to the drug.
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Affiliation(s)
| | | | | | - Rémy Delva
- Institut de Cancérologie de l'Ouest, Centre Paul Papin, Angers, France
| | | | | | | | | | | | - Loïc Mourey
- Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France
| | | | - Jérôme Guitton
- Laboratoire de Pharmacologie Toxicologie, CHU, Lyon, France
| | - Fabienne Thomas
- Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.,Cancer Research Center of Toulouse (CRCT),, Université Paul Sabatier, Toulouse, France
| | | | | | - Sotheara Moeung
- Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.,Cancer Research Center of Toulouse (CRCT),, Université Paul Sabatier, Toulouse, France
| | - Yohan Gallois
- Service d'Otoneurologie et ORL Pédiatrique, Hôpital Pierre Paul Riquet, CHU de Toulouse, Toulouse, France
| | | | | | | | - Etienne Chatelut
- Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.,Cancer Research Center of Toulouse (CRCT),, Université Paul Sabatier, Toulouse, France
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7
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Maillard M, Le Louedec F, Thomas F, Chatelut E. Diversity of dose-individualization and therapeutic drug monitoring practices of platinum compounds: a review. Expert Opin Drug Metab Toxicol 2020; 16:907-925. [PMID: 33016786 DOI: 10.1080/17425255.2020.1789590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Platinum-derived drugs are commonly used for the treatment of solid tumors. The differences in chemical structures of these molecules lead to different pharmacological properties, in terms of indication, efficacy, and toxicity. Their pharmacokinetics (PK) differ according to their respective renal elimination and have led to many studies investigating their dose optimization. Area covered: This review attempts to summarize and compare PK and pharmacodynamics of cisplatin, carboplatin, and oxaliplatin, with an emphasis on differences of dose calculations and opportunities for therapeutic drug monitoring (TDM) in various patient populations. Expert opinion: Although cisplatin and carboplatin can be considered as analogs since they share the same DNA interacting properties, the slower hydrolysis of the latter results in a better safety profile. Carboplatin is the only drug in oncology to be administrated according to a target area under the curve of concentration versus time, considering that its PK variability is almost fully explained by renal function, not by body size. This enables individual dosing based on predicted carboplatin clearance (along with patients renal characteristics) or on actual clearance with TDM, especially in a high-dose protocol.
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Affiliation(s)
- Maud Maillard
- Laboratoire De Pharmacologie, Institut Claudius-Regaud, IUCT-Oncopole , Toulouse Cedex 9, France.,Cancer Research Center of Toulouse, INSERM UMR1037, Team 14 DIAD (Dose Individualization of Anticancer Drug) , Toulouse, France.,Faculté de Pharmacie, Université Paul Sabatier Toulouse III , Toulouse, France
| | - Félicien Le Louedec
- Laboratoire De Pharmacologie, Institut Claudius-Regaud, IUCT-Oncopole , Toulouse Cedex 9, France.,Cancer Research Center of Toulouse, INSERM UMR1037, Team 14 DIAD (Dose Individualization of Anticancer Drug) , Toulouse, France.,Faculté de Pharmacie, Université Paul Sabatier Toulouse III , Toulouse, France
| | - Fabienne Thomas
- Laboratoire De Pharmacologie, Institut Claudius-Regaud, IUCT-Oncopole , Toulouse Cedex 9, France.,Cancer Research Center of Toulouse, INSERM UMR1037, Team 14 DIAD (Dose Individualization of Anticancer Drug) , Toulouse, France.,Faculté de Pharmacie, Université Paul Sabatier Toulouse III , Toulouse, France
| | - Etienne Chatelut
- Laboratoire De Pharmacologie, Institut Claudius-Regaud, IUCT-Oncopole , Toulouse Cedex 9, France.,Cancer Research Center of Toulouse, INSERM UMR1037, Team 14 DIAD (Dose Individualization of Anticancer Drug) , Toulouse, France.,Faculté de Pharmacie, Université Paul Sabatier Toulouse III , Toulouse, France
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8
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Moeung S, Chevreau C, Marsili S, Massart C, Fléchon A, Delva R, Gravis G, Lotz JP, Bay JO, Gross-Goupil M, Filleron T, Delmas C, Lafont T, Chatelut E, Thomas F. Pharmacokinetic and Pharmacogenetic Study of Etoposide in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors. Pharm Res 2020; 37:147. [PMID: 32676789 DOI: 10.1007/s11095-020-02861-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 06/16/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND Etoposide dosing is based on body surface area. We evaluated if further dose individualization would be required for high dose (HD) etoposide within the TI-CE (taxol, ifosfamide, carboplatin, and etoposide) protocol. METHODS Eighty-eight patients received 400 mg/m2/day of etoposide as a 1-hour IV infusion on 3 consecutive days over 3 cycles as part of a phase II trial evaluating efficacy of therapeutic drug monitoring (TDM) of carboplatin in the TI-CE HD protocol. Pharmacokinetic (PK) data were analyzed using population PK model on NONMEM to quantify inter- and intra-individual variabilities. Relationship between etoposide exposure and pharmacodynamic (PD) endpoints, and between selected genetic polymorphisms and tumor response or toxicity were evaluated. RESULTS The inter-patient, inter- and intra-cycle variabilities of clearance were 16%, 9% and 0.1%, respectively. The PK-PD relationship was not significant despite a trend toward higher etoposide exposure in patients responding to treatment. A significant correlation was found between exposure and extended neutropenia at cycle 3. A significant association between UGT1A1*28 polymorphism and late neutropenia was observed but needs further evaluation. CONCLUSIONS The present study suggests that neither a priori dose individualization nor dose adaptation using TDM is required validating body surface area dosing of etoposide in the TI-CE protocol.
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Affiliation(s)
- Sotheara Moeung
- Institut Claudius-Regaud, IUCT-Oncopole, Toulouse, France.,CRCT, Université de Toulouse, Inserm, Toulouse, France
| | | | - Sabrina Marsili
- Institut Claudius-Regaud, IUCT-Oncopole, Toulouse, France.,CRCT, Université de Toulouse, Inserm, Toulouse, France
| | | | | | - Rémy Delva
- Institut De Cancérologie de l'Ouest Paul Papin, Angers, France
| | | | | | | | | | | | - Caroline Delmas
- Institut Claudius-Regaud, IUCT-Oncopole, Toulouse, France.,CRCT, Université de Toulouse, Inserm, Toulouse, France
| | - Thierry Lafont
- Institut Claudius-Regaud, IUCT-Oncopole, Toulouse, France.,CRCT, Université de Toulouse, Inserm, Toulouse, France
| | - Etienne Chatelut
- Institut Claudius-Regaud, IUCT-Oncopole, Toulouse, France. .,CRCT, Université de Toulouse, Inserm, Toulouse, France.
| | - Fabienne Thomas
- Institut Claudius-Regaud, IUCT-Oncopole, Toulouse, France.,CRCT, Université de Toulouse, Inserm, Toulouse, France
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9
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Abstract
More than 80 % of patient with metastatic germ cell tumor are cured with first line chemotherapy. Twenty to 30 % of patients will experience relapse or refractory disease with a very poor long-term prognosis. Most of them had metastatic germ cell tumors with a poor prognosis according to the international germ cell classification collaborative group (IGCCCG). The role of treatment intensification by high dose chemotherapy (HDCT) followed by stem cell rescue has not been demonstrated yet in the first line setting compared to standard chemotherapy. The role of HDCT in first or second salvage is also not yet demonstrated, many studies have been published in this situation with a lot of different regimen. Outside clinical trial, HDCT remains an option in salvage therapy, depending on many factors including prognostics factors, previous therapy, general condition and reference center consideration to select eligible patient who could benefit the most of this approach. Results from the international randomized trial TIGER will provide evidence-based information for HDCT strategy.
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10
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Barnett S, Kong J, Makin G, Veal GJ. Over a decade of experience with carboplatin therapeutic drug monitoring in a childhood cancer setting in the United Kingdom. Br J Clin Pharmacol 2020; 87:256-262. [PMID: 32519769 DOI: 10.1111/bcp.14419] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/27/2020] [Accepted: 04/30/2020] [Indexed: 11/30/2022] Open
Abstract
The widely used platinum agent carboplatin represents a good example of an anticancer drug where clear relationships between pharmacological exposure and clinical response and toxicity have previously been shown. Within the setting of childhood cancer, there are defined groups of patients who present a particular challenge when dosing with carboplatin, including neonates and infants, those who are anephric, and poor prognosis patients receiving high-dose chemotherapy. For these groups, nonstandard chemotherapy dosing regimens are currently utilised, often with different approaches between clinical study protocols and between treatment centres. For the treatment of these patient populations in the UK, there is now significant experience in carrying out therapeutic drug monitoring, aiming to consistently achieve target drug exposures, maximise drug efficacy and minimise treatment-related side effects. An ongoing clinical trial is currently providing information on drug exposure for a wide range of anticancer agents in these hard to treat patient populations. In addition to supporting dosing decisions for individual patients, the collection and analysis of these data may allow the development of future dosing regimens. For example, current reduced dosing approaches for neonates and infants based on age or body weight, may well be better replaced by regimens based on a sound pharmacological rationale. The successful use of adaptive carboplatin dosing in childhood cancer should encourage the development of therapeutic drug monitoring approaches more widely in an oncology setting.
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Affiliation(s)
- Shelby Barnett
- Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Jordon Kong
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Guy Makin
- Division of Cancer Sciences, University of Manchester, Manchester, UK.,Royal Manchester Children's Hospital, Manchester, UK
| | - Gareth J Veal
- Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
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12
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White-Koning M, Paludetto MN, Le Louedec F, Gladieff L, Chevreau C, Chatelut E, Puisset F. Formulae recently proposed to estimate renal glomerular filtration rate improve the prediction of carboplatin clearance. Cancer Chemother Pharmacol 2020; 85:585-592. [DOI: 10.1007/s00280-019-04020-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Accepted: 12/17/2019] [Indexed: 12/21/2022]
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13
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Estimation of Unbound Carboplatin Clearance From Total Plasma Concentrations as a Means of Facilitating Therapeutic Drug Monitoring. Ther Drug Monit 2019; 41:66-74. [DOI: 10.1097/ftd.0000000000000569] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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