Long-Term Complications of Chemotherapy for Germ Cell Tumours
- 1 January 2003
- journal article
- review article
- Published by Springer Science and Business Media LLC in Drugs
- Vol. 63 (15), 1565-1577
- https://doi.org/10.2165/00003495-200363150-00004
Abstract
Testicular cancer is the most common solid tumour among young males aged 15–35 years. Cisplatin-based combination chemotherapy has changed the outlook of this disease. Disseminated testicular cancer, once uniformly fatal, now has a cure rate of more than 80% with combination chemotherapy. Systematic randomised trials have shown that cisplatin, etoposide and bleomycin (PEB) combination chemotherapy remains the mainstay of treatment. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have now been recognised, including secondary leukaemia, therapy-related solid tumours, nephrotoxicity, neurotoxicity, pulmonary toxicity, vascular toxicity and infertility. Etoposide, a DNA topoisomerase II inhibitor, is a significant risk factor for developing leukaemia; the risk appears to be correlated with the total dose given. Patients receiving cisplatin-based combination chemotherapy for testicular cancer also appear to have a higher relative risk for developing second non-germ cell malignancies; the greatest risks for therapy-related solid tumours were seen with a combination of radiation therapy plus chemotherapy. Long-term vascular toxicities associated with chemotherapy include Raynaud’s phenomenon, acute myocardial infarction and cerebrovascular events. Bleomycin is thought to be the most important drug in the pathogenesis of Raynaud’s phenomenon, while cisplatin is the most likely agent involved in myocardial infarction. Peripheral neuropathy is the most common form of neurotoxicity observed with cisplatin-based chemotherapy. Risk factors for the development of neural damage include a high cumulative dose of cisplatin, the use of vinblastine and the concomitant development of Raynaud’s phenomenon. Cisplatin is also well known to cause significant nephrotoxicity. Approximately 25% of patients present with azoospermia after undergoing combination chemotherapy with a follow up of 2–5 years. Physician awareness of complications associated with chemotherapy is vital to maximise efficacy, minimise toxicity, and preserve quality of life after treatment. Sperm cryopreservation should be considered for patients who desire children. Close monitoring during therapy allows for the early diagnosis of complications, and close follow up of patients after the completion of therapy is necessary to monitor for relapse and development of long-term complications such as myelodysplastic syndrome and leukaemia. Despite these complications, given the potential for cure rates in this young group of patients, the benefits far outweigh the risks.Keywords
This publication has 109 references indexed in Scilit:
- Impact of cytotoxic treatment on long-term fertility in patients with germ-cell cancerInternational Journal of Cancer, 1999
- Risk of subsequent non-germ cell cancer after treatment of germ cell cancer in 2006 Norwegian male patientsEuropean Journal of Cancer, 1997
- Enhanced effects of bleomycin on pulmonary function disturbances in patients with decreased renal function due to cisplatinEuropean Journal of Cancer, 1996
- Secondary Leukemia Associated With a Conventional Dose of Etoposide: Review of Serial Germ Cell Tumor ProtocolsJNCI Journal of the National Cancer Institute, 1993
- Prediction of long-term gonadal toxicity after standard treatment for testicular cancerEuropean Journal of Cancer and Clinical Oncology, 1991
- Hematologic Neoplasia Associated with Primary Mediastinal Germ-Cell TumorsNew England Journal of Medicine, 1990
- Treatment of Disseminated Germ-Cell Tumors with Cisplatin, Bleomycin, and either Vinblastine or EtoposideNew England Journal of Medicine, 1987
- Pulmonary complications associated with combination chemotherapy programs containing bleomycinAmerican Journal Of Medicine, 1983
- Low‐dose bleomycin lungMedical and Pediatric Oncology, 1982
- VP16-213 as a single agent in advanced testicular tumorsEuropean Journal of Cancer (1965), 1980