If a patient has refractory or relapsed germ cell tumor after initial cisplatin-based combination chemotherapy, our field debates whether a patient should receive a different salvage combination cisplatin chemotherapy regimen or whether we should move towards high dose chemotherapy with autologous stem cell rescue. Early data showed that there are long term survivors, essentially cures, with stem cell transplant in the 3rd line.3 However, more recent retrospective data from University of Indiana showed rather impressive outcomes with transplant in the 2nd line.4 There was a definitive study evaluating the role of transplant as first line therapy for patients with intermediate- or poor-risk features, resulting in no benefit over standard bleomycin, etoposide and cisplatin (BEP) chemotherapy.5 However, it is unknown whether transplant offers benefit over salvage chemotherapy in the 2nd line. The Alliance Cooperative Group in the United States is performing a large randomized trial in this setting testing standard dose salvage chemotherapy vs. high dose chemotherapy with stem cell transplant (Trial 1). Hopefully, this should answer the question as to what we should do to help patients with refractory or relapsed disease.
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Even though outcomes are outstanding for most men with germ cell tumors, our field must continue to explore biology and mechanisms of resistance for refractory disease. This includes advocacy and academic partnerships with industry to design more clinical trials of novel agents. Although limited in numbers, we should encourage patient enrollment to clinical trials in these situations where we anticipate sub-optimal outcomes. This should serve as a reminder to our field that outcomes for this disease were not always outstanding until combination cisplatin-based chemotherapy regimens were developed. Only through clinical trials will we discover the next wave of therapeutics for those patients with a limited prognosis due to relapsed/refractory germ cell tumors.
Written by: Evan Yu, MD
- Standard dose salvage chemotherapy vs. high dose chemotherapy with stem cell transplant
- Brentuximab vedotin
- Brentuximab vedotin combined with Bevacizumab
- Durvalumab combined with Tremelimumab
- Sirolimus combined with Erlotinib
- Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
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