Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors

Autor: Loic Mourey, Christophe Massard, Remy Delva, Joseph Ciccolini, Fabienne Thomas, Christine Chevreau, Thomas Filleron, Jean-Pierre Lotz, Stéphane Culine, Gwenaelle Gravis, Marine Gross-Goupil, Etienne Chatelut, Aude Flechon, Angelo Paci, Jacques-Olivier Bay, Jérôme Guitton, Sotheara Moeung, Yohan Gallois, Pascale Olivier, Bénédicte Lelièvre, Karim Fizazi
Přispěvatelé: Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CRLCC Paul Papin, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Hôpital Saint-André, Direction de la recherche [Gustave Roussy], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de la Timone [CHU - APHM] (TIMONE), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Hôpital Pierre-Paul Riquet [Toulouse], CHU Toulouse [Toulouse], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cancer Research
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Carboplatin
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
germ cell tumors
phase II trial
Etoposide
ComputingMilieux_MISCELLANEOUS
Original Research
education.field_of_study
Ifosfamide
medicine.diagnostic_test
Area under the curve
Middle Aged
Neoplasms
Germ Cell and Embryonal
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Survival Rate
Treatment Outcome
Oncology
Area Under Curve
030220 oncology & carcinogenesis
high‐dose chemotherapy
Drug Monitoring
medicine.drug
Adult
medicine.medical_specialty
Paclitaxel
therapeutic drug monitoring
Population
relapsed patients
Urology
lcsh:RC254-282
Young Adult
03 medical and health sciences
medicine
Humans
Radiology
Nuclear Medicine and imaging
education
Salvage Therapy
Chemotherapy
Dose-Response Relationship
Drug
business.industry
Clinical Cancer Research
Regimen
030104 developmental biology
chemistry
Drug Resistance
Neoplasm
Therapeutic drug monitoring
Neoplasm Recurrence
Local
business
high-dose chemotherapy
Zdroj: Cancer Medicine
Cancer Medicine, Wiley, 2021, 10 (7), pp.2250-2258. ⟨10.1002/cam4.3687⟩
Cancer Medicine, Vol 10, Iss 7, Pp 2250-2258 (2021)
ISSN: 2045-7634
Popis: 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.
The superiority of HDCT over standard chemotherapy as initial salvage treatment of patients with relapsed or refractory germ cell tumors remains a valid question. In the TI‐CE regimen, TDM was demonstrated to be feasible in routine practice and really allowed to control target AUC more accurately compared to previous reports, avoiding both underexposure and overexposure to carboplatin. In our study, the rate of CR observed in this population with very poor prognosis was 44.3% and increased to 69.6% of favorable responses. Based on our study and if the benefit of HDCT is proven in the TIGER trial, we suggest that the use of carboplatin TDM for dose individualization in current practice should be considered.
Databáze: OpenAIRE
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