Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial

K. Fizazi 1 G. Gravis 2 A. Flechon 3 L. Geoffrois 4 C. Chevreau 5 B. Laguerre 6 R. Delva 7 J. C. Eymard 8 F. Rolland 9 Nadine Houédé 10, 11, 12 A. Laplanche 13 D. Burcoveanu 13 S. Culine 14
1 Département de médecine oncologique [Gustave Roussy]
2 Institut Paoli-Calmettes
3 Centre Léon Bérard [Lyon]
4 ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin
5 Institut Claudius Regaud
6 CRLCC - CRLCC Eugène Marquis
7 ICO - Paul Papin - Institut de cancérologie de l'Ouest - Paul Papin
8 CRLCC Jean Godinot
9 CRLCC René Gauducheau
10 CHRU Nîmes - Centre Hospitalier Régional Universitaire de Nîmes
11 Institut Bergonié - CRLCC Bordeaux
12 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier
13 SBE - Service de biostatistique et d'épidémiologie
14 Hôpital Saint-Louis
Abstract : BACKGROUND: The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate \textless50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study. PATIENTS AND METHODS: The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 mug/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used. RESULTS: Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression. CONCLUSION: In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate. CLINICAL TRIAL NUMBER: NCT00127049.
Keywords : Testicular Neoplasms/*drug therapy/mortality/pathology Germ Cell and Embryonal/*drug therapy/mortality/secondary Neoplasms Local/*drug therapy Neoplasm Recurrence Deoxycytidine/administration & dosage/analogs & derivatives Ifosfamide/administration & dosage Humans Middle Aged Adult Male Treatment Outcome Young Adult Prospective Studies Kaplan-Meier Estimate Lymphatic Metastasis Salvage Therapy Drug Administration Schedule Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Cisplatin/administration & dosage
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https://hal.umontpellier.fr/hal-02168058
Contributeur : Cécile Nowak <>
Soumis le : vendredi 28 juin 2019 - 13:49:51
Dernière modification le : mercredi 7 août 2019 - 13:48:04

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UNIV-MONTPELLIER | ICR | BERGONIE | VALDAURELLE | PAOLI_CALMETTES | VAUTRIN | ICO | MARQUIS | GAUDUCHEAU | FNCLCC | GODINOT | BS | IRCM | UNIV-PARIS7 | USPC | IGR

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K. Fizazi, G. Gravis, A. Flechon, L. Geoffrois, C. Chevreau, et al.. Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial. Annals of Oncology, Oxford University Press (OUP), 2014, 25, pp.987--91. ⟨10.1093/annonc/mdu099⟩. ⟨hal-02168058⟩

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