In fact, oxaliplatin has previously been studied in this setting, and combination treatments are underway. Soulié et al. [2] reported a series of 13 patients who received an oxaliplatin-based regimen from 1992 to 1995 as part of a compassionate-use program for relapsed/refractory NSGCT. Patients received oxaliplatin 130 mg/m2 and cisplatin 100 mg/m2, in combination with other drugs and alone. This study demonstrated that responses can occur in cisplatin-refractory patients (four responses in eight patients) using an oxaliplatin-based regimen. Furthermore, it provided information which showed that oxaliplatin can be safely combined with potentially active drugs in NSGCT. However, until the trial reported by the German group [1
], there were no published data on single-agent use of oxaliplatin in NSGCT. From September 1997 to October 1999, eight patients with cisplatin-refractory (n=6) or relapsed (n=2) NSGCT also received single-agent oxaliplatin (130 mg/m2 every 3 weeks) at the Institut Gustave Roussy, Villejuif, France. These patients had received a median of two (range one to four) previous regimens. Among them, three out of eight achieved an improvement: one had a partial response with normalization of tumor markers, one had a partial response (tumor markers were normal at baseline), and one had a reduction of 50% of serum human chorionic gonadotropin while on single-agent oxaliplatin. These data confirmed those of the German trial [1
], showing activity in the advanced stages of the disease.
A much higher activity of oxaliplatin is expected in combination regimens based on both preclinical data [3] and the clinical experience accumulated in other neoplasms [4
, 5
]. In certain models, synergy of oxaliplatin with other drugs and non cross-resistance with cisplatin are observed. This was the rationale for a French phase II trial of the oxaliplatinpaclitaxel combination in relapsed/refractory NSGCT, for which accrual is now over and first results are expected soon. Oxaliplatin was also combined with gemcitabine in a phase II trial conducted by the German group [6
]. The overall responses rate in 35 relapsed/refractory GCT patients was 46%, including three complete responses.
Based on these promising results, we have incorporated oxaliplatin in an international phase III trial in which patients with poor-risk NSGCT and an unfavorable decline of tumor markers [7] are randomized between the bleomycin, cisplatin, etoposide (BEP) regimen and a dose-dense regimen including oxaliplatin. This trial began in November 2003. It may contribute to better defining the role of oxaliplatin in the treatment of NSGCT.
1 Department of Medicine, Institut Gustave Roussy, Villejuif; 2 Centre Val d'Aurelle, Montpellier, France 3 Department of Genitourinary Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA
* Email: fizazi{at}igr.fr
References
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2. Soulié P, Garrino C, Bensmaine MA et al. Antitumoral activity of oxaliplatin/cisplatin-based combination therapy in cisplatin-refractory germ cell cancer patients. J Cancer Res Clin Oncol 1999; 125: 707711.[CrossRef][ISI][Medline]
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