Multicentric phase II trial of TI-CE high-dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors.
Adult
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Area Under Curve
Carboplatin
/ administration & dosage
Dose-Response Relationship, Drug
Drug Monitoring
/ methods
Drug Resistance, Neoplasm
Etoposide
/ administration & dosage
Humans
Ifosfamide
/ administration & dosage
Male
Middle Aged
Neoplasm Recurrence, Local
/ blood
Neoplasms, Germ Cell and Embryonal
/ blood
Paclitaxel
/ administration & dosage
Salvage Therapy
Survival Rate
Treatment Outcome
Young Adult
germ cell tumors
high-dose chemotherapy
phase II trial
relapsed patients
therapeutic drug monitoring
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
28
09
2020
received:
28
07
2020
accepted:
07
11
2020
pubmed:
7
3
2021
medline:
27
7
2021
entrez:
6
3
2021
Statut:
ppublish
Résumé
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. 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. 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%. 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.
Sections du résumé
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.
Identifiants
pubmed: 33675184
doi: 10.1002/cam4.3687
pmc: PMC7982623
doi:
Substances chimiques
Etoposide
6PLQ3CP4P3
Carboplatin
BG3F62OND5
Paclitaxel
P88XT4IS4D
Ifosfamide
UM20QQM95Y
Banques de données
ClinicalTrials.gov
['NCT00864318']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2250-2258Informations de copyright
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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