Antitumoral activity of oxaliplatin/cisplatin-based combination therapy in cisplatin-refractory germ cell cancer patients

J Cancer Res Clin Oncol. 1999 Dec;125(12):707-11. doi: 10.1007/s004320050338.

Abstract

Purpose: Only 20-30% of patient with advanced germ cell tumors, relapsing after standard first-line therapy, are curable with current second-line cisplatin-based regimens. New salvage combinations incorporating new active agents are needed. We report the toxicity/tolerance of a new salvage regimen based on the oxaliplatin (Eloxatin)/cisplatin combination, evaluated in patients with recurrent, mostly cisplatin-refractory germ cell tumors.

Patients and methods: Thirteen patients were enrolled in this study. All except one had received cisplatin-based chemotherapy. Eight had progressive disease as the best response on their last platinum-based chemotherapy, and three had potentially sensitive tumors. The median interval since the last platinum-based chemotherapy was 6 months (range: 1-36 months). One untreated patient with poor prognosis was also enrolled. Twelve patients had pathological markers [median alpha-fetoprotein 14 800 ng/ml (58-10(6)), median human chorionic gonadotrophin beta subunit 7000 IU/ml (37-723 700)]. Patients received either oxaliplatin (130 mg/m(2)) and cisplatin (100 mg/m(2)) every 3-4 weeks (Bi regimen, four patients), or the same regimen combined with one to four of the following cytotoxic agents: ifosfamide, epirubicin, vinorelbine, methotrexate, dactinomycin, etoposide and bleomycin (BiC regimen, 9 patients). Treatment was individualized according to each individual patient's pretreatment and clinical characteristics.

Results: Seven objective responses were obtained (overall response rate = 54%), all with the BiC regimens (two complete and five partial responses). Two patients with recurrent disease achieved a long-term complete response lasting over 5 years. Four partial responders were seen in the eight cisplatin-refractory tumors, lasting 4-8 months. All objective responses had a corroborating major decrease in tumor marker blood levels (median decrease: 99.7%). The median survival for the whole group was 8 months. The commonest severe toxicity was hematological (grade 4 neutropenia in 78% and thrombopenia in 74% of the BiC cycles).

Conclusion: Our combined salvage regimen induced significant antitumoral activity in recurrent, cisplatin-refractory germ cell tumors. Oxaliplatin merits further evaluation as a component of combination therapy for this disease.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / therapeutic use
  • Chorionic Gonadotropin, beta Subunit, Human / blood
  • Chorionic Gonadotropin, beta Subunit, Human / drug effects
  • Cisplatin / therapeutic use*
  • Dactinomycin / therapeutic use
  • Drug Resistance, Neoplasm
  • Drug Therapy, Combination
  • Epirubicin / therapeutic use
  • Etoposide / therapeutic use
  • Germinoma / drug therapy*
  • Humans
  • Ifosfamide / therapeutic use
  • Male
  • Neoplasm Recurrence, Local
  • Neutropenia / chemically induced
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Salvage Therapy
  • Testicular Neoplasms / drug therapy*
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Vinblastine / analogs & derivatives
  • Vinblastine / therapeutic use
  • Vinorelbine
  • alpha-Fetoproteins / drug effects
  • alpha-Fetoproteins / metabolism

Substances

  • Chorionic Gonadotropin, beta Subunit, Human
  • Organoplatinum Compounds
  • alpha-Fetoproteins
  • Oxaliplatin
  • Bleomycin
  • Dactinomycin
  • Epirubicin
  • Vinblastine
  • Etoposide
  • Cisplatin
  • Vinorelbine
  • Ifosfamide