Advanced
germ cell cancer can be cured in most patients using
chemotherapy with or without surgery. A small fraction of patients with nonseminomatous
tumors (NSGCT) and an even smaller percentage of
seminoma patients are destined to have a less favorable outcome, due to an inadequate response to first-line
chemotherapy (failure to achieve remission, finding of residual viable
carcinoma at post-
chemotherapy surgery, or relapse after achieving a remission). Despite the apparent salvage potential for regimens containing
ifosfamide or
paclitaxel, no proof exists that such combinations are superior to the standard regimen of four cycles of
cisplatin,
etoposide, and
bleomycin (PEB) in the front-line
therapy of patients with advanced NSGCT. Other modifications of first-line
therapy, such as the addition of
paclitaxel or the use of escalated doses of
cisplatin, also have failed to increase the cure rate. The use of single or tandem cycles of high-dose
chemotherapy (HDT with autologous hematopoietic cell transplant [aHCT]) in various settings (for selected patients with poor prognostic features before
therapy, patients predicted to have a poor outcome based on the rate of serum
tumor marker decline while on
therapy, and patients in relapse or failure to achieve adequate response to standard
therapy) has been evaluated in many phase II and a limited number of phase III trials, which are summarized in this review. Important questions that remain to be answered include the role of new agents and the use of more sophisticated techniques to understand prognostic and predictive factors in selecting
therapy for GCT.