One hundred and eighty-five studies (number of participants not reported) were included in the review. There were 68 studies on chemotherapy regimens, including first-line treatment (24 RCTs), second-line treatment (2 RCTs, 12 prospective phase 2 studies, 6 retrospective studies and 1 retrospective matched pair study) and post chemotherapy surgery (22 retrospective studies); 17 studies on late relapse (retrospective series); and 104 studies on toxic effects (4 RCTs and 100 retrospective series).
In the initial management of metastatic GCT, approximately 90% of patients classified as having good prognosis achieved a complete remission to either 4 cycles of etoposide and cisplatin or 3 cycles of cisplatin, etoposide and bleomycin. Complete response was less frequent in patients with intermediate- and poor-risk (55 to 82%) GCTs with standard care comprising 4 cycles of bleomycin, etoposide, and cisplatin.
Second- and third-line treatment regimens were also found to have curative potential. Successful approaches included either standard doses of 3-drug combinations based on ifosfamide and cisplatin or high-dose chemotherapy with autologous stem-cell support. Durable response rates with conventionally dosed salvage regimens (e.g. ifosfamide and cisplatin plus either vinblastine or etoposide) ranged from 7 to 26%. A durable response rate of 63% was found for the combination of paclitaxel, ifosfamide and cisplatin, with a median follow-up of 69 months. Limited data exist to guide the choice of high-dose or conventional-dose chemotherapy for initial salvage treatment; one prospective trial found no significant difference in 3-year event-free and overall survival between the two approaches, while one retrospective study found a 10% benefit in 2-year disease-free and overall survival with high-dose therapy.
A 2 to 6% incidence rate of 'late relapse' (relapse, in the absence of a second primary testicular cancer, at least 2 years after treatment completion) was found. The majority of late relapses occur more than 5 years (median 5 to 10 years) following the completion of treatment, with the latest relapse occurring 32 years after treatment completion.
Acute toxicities associated with the most commonly used chemotherapy treatments of GCT include myelosuppression leading to febrile neutropenia, bleeding and anaemia. GCT chemotherapy has also been linked to acute cardiovascular and thromboembolic events. Acute adverse events of bleomycin included pulmonary toxicity and Raynaud phenomenon. Select toxic effects of other chemotherapy drugs used to treat GCT were also reported. Chronic toxicity associated with treatment included cardiovascular disease, infertility and secondary malignancies.