Diethyldithiocarbamate chemoprotection of carboplatin-induced hematological toxicity

Carboplatin therapy has a more favorable toxicity profile than cisplatin and, given in appropriate doses, is equivalent in efficacy to cisplatin for suboptimal ovarian cancer. However myelosuppression frequently curtails therapy with carboplatin. Diethyldithiocarbamate (DDTC) is a thiol compound and heavy-metal-chelating agent that has been shown to protect against carboplatin-induced bone marrow suppression in animal models. This pilot study was undertaken to evaluate the ability of DDTC to ameliorate the degree and/or duration of myelosuppression from carboplatin chemotherapy in patients with relapsed ovarian cancer. Ten patients who had previously demonstrated a response to platinum-based chemotherapy, were treated with single-agent intravenous carboplatin 400 mg/m² administered over 30-60 min every 4 weeks. Patients received their first cycle of carboplatin without DDTC, and their second cycle with DDTC. DDTC at 600 mg/m² was infused over 3 h commencing 30 min prior to carboplatin and was well tolerated. Treatment with DDTC did not decrease the degree of leukopenia or thrombocytopenia associated with carboplatin chemotherapy, nor did it decrease the duration of myelosuppression. This clinical study demonstrates no evidence of a bone-marrow-protective effect for this dose and schedule of DDTC in patients receiving carboplatin chemotherapy.