High dose chemotherapy and stem cell support in the treatment of germ cell cancer

The current status of high dose chemotherapy with autologous stem cell support in patients with germ cell cancer is reviewed.

Advanced germ cell cancer can be cured in most patients using chemotherapy with or without surgery. A small fraction of patients fail to achieve a marker remission, have residual viable carcinoma at post-chemotherapy surgery or have relapse after remission. Phase II trials suggest that autologous stem cell support is more active than standard dose chemotherapy in patients with relapse. A comprehensive literature review, focusing on trials published in the last decade, is followed by a discussion of current trials and recommendations for the use of autologous stem cell support in germ cell cancer.

In early trials about 15% of patients with multiple relapsed and refractory disease had durable remission with high dose carboplatin and etoposide. Most regimens now add high dose cyclophosphamide or ifosfamide to carboplatin and etoposide. Together with the use of autologous stem cell support in less heavily-pretreated patients, these regimens have produced durable remissions in 40% to 50% of patients. Multivariate analyses led to the identification of prognostic factors at diagnosis and predictive factors during therapy which were associated with a low rate of durable remission. Ongoing randomized trials of autologous stem cell support early in relapse or as part of initial therapy are designed to study and validate further these prognostic factors.

For patients with poor risk presenting features, the role of autologous stem cell support has not been proven and awaits the results of an ongoing United States intergroup trial. Patients with residual cancer at post-chemotherapy surgery may have a substantial risk of relapse despite additional cycles of the same drugs used to achieve marker remission. For select patients in this category alternatives to additional cycles of the original chemotherapy may include established second line regimens or autologous stem cell support. The role of autologous stem cell support for germ cell tumor in relapse may be challenged by the future discovery of new agents for these diseases.