Annals of Oncology 15:1295, 2004
© 2004 European Society for Medical Oncology
Oxaliplatin in non-seminomatous germ-cell tumors
Recently, Kollmannsberger et al. [1
] reported the final results of a phase II trial of oxaliplatin as a single agent in patients with relapsed or refractory non-seminomatous germ-cell tumors (NSGCT) treated from 1998 to 2001. The authors concluded that oxaliplatin is an active agent and that it should be evaluated in combination regimens.
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 oxaliplatin–paclitaxel 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
1. Kollmannsberger C, Rick O, Derigs HG et al. Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol 2002; 20: 2031–2037.
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: 707–711.[CrossRef][Web of Science][Medline]
3. Rixe O, Ortuzar W, Alvarez M et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's Anticancer Drug Screen panel. Biochem Pharmacol 1996; 52: 1855–1865.[CrossRef][Web of Science][Medline]
4. Fizazi K, Ducreux M, Ruffie P et al. Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer. J Clin Oncol 2000; 18: 2293–2300.
5. Soulié P, Bensmaine A, Garrino C et al. Oxaliplatin/cisplatin (L-OHP/CDDP) combination in heavily pretreated ovarian cancer. Eur J Cancer 1997; 33: 1400–1406.[CrossRef][Medline]
6. Fizazi K, Kramar A, Culine S et al. The early decline of tumor markers predicts outcome in poor-prognosis non-seminomatous germ-cell tumors (NSGCT). Results of a multi-Institution Study. Proc Am Soc Clin Oncol 2002; 21: 185a.
7. Kollmannsberger C, Beyer J, Liersch R et al. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol 2004; 22: 108–114.
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