Abstract
Background
The purpose of this study is to assess the feasibility of salvage chemotherapy with gemcitabine and oxaliplatin (GEMOX) for Japanese patients with refractory testicular germ cell cancer.
Methods
Eleven patients were treated with GEMOX. All had experienced disease progression or recurrence and had been treated with the standard induction chemotherapy and at least one cycle of cisplatin-based salvage chemotherapy (median 6 cycles) before the start of GEMOX. GEMOX consisted of gemcitabine 1,000 mg/m2 intravenously on days 1 and 8 and oxaliplatin 130 mg/m2 on day 1.
Results
Two patients (18 %) achieved a complete response (CR) after GEMOX and surgical resection of residual tumor. One additional patient responded to GEMOX, but was forced to discontinue treatment due to sensory neuropathy. This patient achieved CR after further treatment with irinotecan-based chemotherapy and surgery. All three patients have remained continuously free from disease progression at a median follow-up duration of 24 months. Sixty-four per cent of patients developed grade 3 leukocytopenia and 82 % developed grade 3 or higher thrombocytopenia but they were all managed with routine supportive care. Sensory neuropathy was frequently seen but no patient experienced neurotoxicity higher than grade 3.
Conclusions
GEMOX as salvage chemotherapy is tolerable for intensively pretreated Japanese patients. GEMOX may offer a chance of long-term disease-free status even after failure of multiple cycles of chemotherapy.
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References
Bokemeyer C, Gerl A, Schöffski P et al (1999) Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer. J Clin Oncol 17:512–516
Kollmannsberger C, Rick O, Derigs HG et al (2002) 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 20:2031–2037
Hinton S, Catalano P, Einhorn LH et al (2002) Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 20:1859–1863
Motzer RJ, Sheinfeld J, Mazumdar M et al (2000) Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol 18:2413–2418
Einhorn LH, Brames MJ, Juliar B et al (2007) Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol 25:513–516
Kollmannsberger C, Beyer J, Liersch R et al (2004) 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 22:108–114
Pectasides D, Pectasides M, Farmakis D et al (2004) Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol 15:493–497
De Giorgi U, Rosti G, Aieta M et al (2006) Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol 50:1032–1038
Theodore C, Chevreau C, Yataqhene Y et al (2008) A phase II multicenter study of oxaliplatin in combination with paclitaxel in poor prognosis patients who failed cisplatin-based chemotherapy for germ-cell tumors. Ann Oncol 19:1465–1469
Oechsle K, Kollmannsberger C, Honecker F et al (2011) Long-term survival after treatment with gemcitabine and oxaliplatin with and without paclitaxel plus secondary surgery in patients with cisplatin-refractory and/or multiply relapsed germ cell tumors. Eur Urol 60:850–855
Takimoto CH, Graham MA, Lockwood G et al (2007) Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function. Clin Cancer Res 13:4832–4839
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247
Miki T, Mizutani Y, Nonomura N et al (2002) Irinotecan plus cisplatin has substantial antitumor effect as salvage chemotherapy against germ cell tumors. Cancer 95:1879–1885
Dunn TA, Schmoll HJ, Grünwald V et al (1997) Comparative cytotoxicity of oxaliplatin and cisplatin in non-seminomatous germ cell cancer cell lines. Invest New Drugs 15:109–114
Fink D, Nebel S, Aebi S et al (1996) The role of DNA mismatch repair in platinum drug resistance. Cancer Res 56:4881–4886
Faivre S, Raymond E, Woynarowski JM et al (1999) Supraadditive effect of 2′,2′-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol 44:117–123
Hellberg V, Wallin I, Eriksson S et al (2009) Cisplatin and oxaliplatin toxicity: importance of cochlear kinetics as a determinant for ototoxicity. J Natl Cancer Inst 101:37–47
Pasetto LM, D’Andrea MR, Rossi E et al (2006) Oxaliplatin-related neurotoxicity: how and why? Crit Rev Oncol Hematol 59:159–168
Hewitt MR, Sun W (2006) Oxaliplatin-associated hypersensitivity reactions: clinical presentation and management. Clin Colorectal Cancer 6:114–117
Siu SW, Chan RT, Au GK (2006) Hypersensitivity reactions to oxaliplatin: experience in a single institute. Ann Oncol 17:259–261
Acknowledgments
This work was supported in part by a Grant-in-Aid for Scientific Research(C) (24592376) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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The authors declare that they have no conflict of interest.
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Uchida, M., Kawai, K., Kimura, T. et al. Salvage chemotherapy with gemcitabine plus oxaliplatin for patients with testicular germ cell cancer. Int J Clin Oncol 19, 1112–1117 (2014). https://doi.org/10.1007/s10147-014-0667-5
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DOI: https://doi.org/10.1007/s10147-014-0667-5