Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors
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 wi...
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3687 |
| _version_ | 1818649071833841664 |
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| author | Christine Chevreau Christophe Massard Aude Flechon Rémy Delva Gwenaëlle Gravis Jean‐Pierre Lotz Jacques‐Olivier Bay Marine Gross‐Goupil Karim Fizazi Loïc Mourey Angelo Paci Jérôme Guitton Fabienne Thomas Bénédicte Lelièvre Joseph Ciccolini Sotheara Moeung Yohan Gallois Pascale Olivier Stéphane Culine Thomas Filleron Etienne Chatelut |
| author_facet | Christine Chevreau Christophe Massard Aude Flechon Rémy Delva Gwenaëlle Gravis Jean‐Pierre Lotz Jacques‐Olivier Bay Marine Gross‐Goupil Karim Fizazi Loïc Mourey Angelo Paci Jérôme Guitton Fabienne Thomas Bénédicte Lelièvre Joseph Ciccolini Sotheara Moeung Yohan Gallois Pascale Olivier Stéphane Culine Thomas Filleron Etienne Chatelut |
| author_sort | Christine Chevreau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:28:30Z |
| format | Article |
| id | doaj.art-301fe9ecb34d4726a60f64295b13ac50 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-17T01:28:30Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-301fe9ecb34d4726a60f64295b13ac502022-12-21T22:08:39ZengWileyCancer Medicine2045-76342021-04-011072250225810.1002/cam4.3687Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumorsChristine Chevreau0Christophe Massard1Aude Flechon2Rémy Delva3Gwenaëlle Gravis4Jean‐Pierre Lotz5Jacques‐Olivier Bay6Marine Gross‐Goupil7Karim Fizazi8Loïc Mourey9Angelo Paci10Jérôme Guitton11Fabienne Thomas12Bénédicte Lelièvre13Joseph Ciccolini14Sotheara Moeung15Yohan Gallois16Pascale Olivier17Stéphane Culine18Thomas Filleron19Etienne Chatelut20Institut Claudius RegaudIUCT‐Oncopole Toulouse FranceInstitut Gustave Roussy Villejuif FranceCentre Léon Bérard Lyon FranceInstitut de Cancérologie de l’Ouest Centre Paul Papin Angers FranceInstitut Paoli Calmettes Marseille FranceHôpital Tenon Paris FranceCHU de Clermont‐Ferrand FranceHôpital Saint‐André Bordeaux FranceInstitut Gustave Roussy Villejuif FranceInstitut Claudius RegaudIUCT‐Oncopole Toulouse FranceInstitut Gustave Roussy Villejuif FranceLaboratoire de Pharmacologie ToxicologieCHU Lyon FranceInstitut Claudius RegaudIUCT‐Oncopole Toulouse FranceLaboratoire de Pharmacologie Toxicologie CHU Angers FranceCHU La Timone Marseille FranceInstitut Claudius RegaudIUCT‐Oncopole Toulouse FranceService d'Otoneurologie et ORL Pédiatrique Hôpital Pierre Paul RiquetCHU de Toulouse Toulouse FranceInstitut Claudius RegaudIUCT‐Oncopole Toulouse FranceHôpital Saint‐Louis Paris FranceInstitut Claudius RegaudIUCT‐Oncopole Toulouse FranceInstitut Claudius RegaudIUCT‐Oncopole Toulouse FranceABSTRACT 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.https://doi.org/10.1002/cam4.3687germ cell tumorshigh‐dose chemotherapyphase II trialrelapsed patientstherapeutic drug monitoring |
| spellingShingle | Christine Chevreau Christophe Massard Aude Flechon Rémy Delva Gwenaëlle Gravis Jean‐Pierre Lotz Jacques‐Olivier Bay Marine Gross‐Goupil Karim Fizazi Loïc Mourey Angelo Paci Jérôme Guitton Fabienne Thomas Bénédicte Lelièvre Joseph Ciccolini Sotheara Moeung Yohan Gallois Pascale Olivier Stéphane Culine Thomas Filleron Etienne Chatelut 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 Medicine germ cell tumors high‐dose chemotherapy phase II trial relapsed patients therapeutic drug monitoring |
| title | Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors |
| title_full | Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors |
| title_fullStr | Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors |
| title_full_unstemmed | Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors |
| title_short | Multicentric phase II trial of TI‐CE high‐dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors |
| title_sort | multicentric phase ii trial of ti ce high dose chemotherapy with therapeutic drug monitoring of carboplatin in patients with relapsed advanced germ cell tumors |
| topic | germ cell tumors high‐dose chemotherapy phase II trial relapsed patients therapeutic drug monitoring |
| url | https://doi.org/10.1002/cam4.3687 |
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