Shamash J et al. (2007) GAMEC—a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours. Br J Cancer 97: 308–314

The optimum treatment regimen for patients with untreated poor-prognosis or relapsed germ cell tumors (GCT) is currently a matter of some debate. In a recent paper, researchers from St Bartholomew's Hospital, London, UK, describe a novel intensive protocol that is highly active in GCT.

Between September 1997 and June 2005, 27 patients with untreated poor-prognosis GCT, and 35 patients with relapsed GCT following conventional platinum-based therapy, were enrolled in a phase II trial of a novel intensive regimen. The cisplatin-based protocol—GAMEC—incorporated dactinomycin, etoposide and high-dose methotrexate, administered every 14 days. Following GAMEC administration and appropriate surgery, 74% of the previously untreated group and 51% of the previously treated group were progression-free at a median follow-up of 2.5 years. Furthermore, one patient in the previously untreated group and four patients in the pretreated group were salvaged by additional therapy. Unfortunately, the toxicity associated with the GAMEC regimen was considerable, with many cycles of therapy being complicated by cases of febrile neutropenia, approximately half of which required platelet transfusion. Overall, there were five treatment-related deaths—four owing to sepsis and one to intra-abdominal hemorrhage from choriocarcinoma. In the pretreated group, methotrexate dose density was significantly associated with progression-free survival (P = 0.003). Notably, neither the Memorial Sloan–Kettering Cancer Center criteria nor the Medical Research Council criteria for relapsed GCT were able to identify a poor-prognostic group for GAMEC.

The authors conclude that GAMEC is an effective treatment for patients with untreated or relapsed GCT, although it results in substantial toxic effects.