Late toxicity following curative treatment of testicular cancer

Abstract

Cisplatin appears to be the major cause for long‐term toxicity in patients treated for testicular cancer. Long‐term side effects consist mainly of nephrotoxicity, ototoxicity, and neurotoxicity as well as gonadal damage. Following standard‐dose chemotherapy approximately 20% to 30% of patients will be affected by long‐term side effects, although not all these side effects will cause an impaired quality of life. Several strategies have been or currently are being evaluated to reduce acute and long‐term complications including the introduction of equally effective, but less toxic regimens, or the use of cytoprotective agents such as amifostine. Secondary acute myeloid leukemia and secondary myelodysplastic syndrome probably represent the worst possible long‐term complications of cancer therapy in those patients who originally were cured of their primary testicular cancer. Therapy‐related solid tumors are mainly associated with the use of radiation therapy and the risk for developing a therapy‐related solid tumor is increased approximately two to three times compared to the general population. In contrast, therapy‐related leukemias are predominantly associated with chemotherapy, particularly with the use of topoisomerase‐II inhibitors and alkylating agents. In general, the cumulative incidence of therapy‐related leukemia following treatment of germ cell cancer is low. It is approximately 0.5% and 2% at 5 years of median follow‐up for patients receiving etoposide at cumulative doses≤2 g/m2 and >2 g/m2, respectively. The risk‐benefit analysis in patients with testicular cancer clearly favors the use of current treatment regimens including high‐dose chemotherapy. However, even the acceptably low number of therapy‐related long‐term complications should encourage the search for equally effective but less toxic therapies. This review will highlight important available data about therapy‐related toxicity and particularly, therapy‐related malignancies following cisplatin‐etoposide‐based chemotherapy. Semin. Surg. Oncol. 17:275–281, 1999. © 1999 Wiley‐Liss, Inc.

NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: A HuGE review

“…9,50 There are numerous documented cases of individuals receiving chemotherapy with alkylating agents who develop secondary myeloid leukemia. [51][52][53] The NQO1*2 allelic frequency was found to be higher in these individuals than in patients who received chemotherapy but did not develop secondary malignancies, 54,55 implicating NQO1 in some chemical-induced leukemias.…”

Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype

“…In addition, the risk of developing cardiovascular disease is more than twice as high among testicular cancer treatment survivors relative to age-matched controls (Huddart et al 2003). Other therapy-related complications include nephrotoxicity, neuropathy, and ototoxicity due to cisplatin, as well as pulmonary toxicity from bleomycin (Kollmannsberger et al 1999). Post-treatment sexual dysfunction is not uncommon (van Basten et al 1997, Huddart et al 2005).…”

Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD

“…Administration of multiple cycles leads to permanent and irreversible loss of kidney function, 17,18 but the cause of this progressive form of CKD is unknown. Prior studies suggest multifactorial mechanisms, including induction of apoptotic and cellular repair pathways, oxidative stress, and inflammatory responses.…”