Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma

Dolastatin-10 is a natural, cytotoxic peptide with microtubule-inhibitory a nd apoptotic effects. It has demonstrated ill vitro and in vivo efficacy in the DU-145 human prostate cancer model. A Phase II clinical trial was desi gned in patients with hormone-refractory prostate cancer, Dolastatin-10 was administered at a dose of 400 mug/m(2) i.v. every 3 weeks. Dose escalation to 450 mug/m(2) was permitted, Toxicity evaluation was conducted every 2 w eeks, and assessment of response was done at the end of every two cycles, S ixteen patients were enrolled between October 1998 to December 1999. The me dian age was 71 Sears (range, 59-79 years). Median prostate-specific antige n value was 108 ng/ml (range, 15.3-1672 ng/ml). Of the 15 eligible patients , 7 were Caucasian and 8 were African-American. Eight patients had bone-onl y metastases, and seven had measurable disease with or without bone metasta ses, A total of 56 cycles have been administered. Only 2 patients required dose adjustment because of toxicity, and in 5 patients, dose escalation was feasible to 450 mug/m(2). The major toxicities observed were grade 3 and 4 neutropenia in 8 patients and grade 3 neuropathy in 1 patient, All 15 pati ents are evaluable for response. Three patients demonstrated stable disease ; 2 of these had bone disease, and 1 had nodal metastasis, All others had d isease progression, Dolastatin-10 is very well tolerated in this elderly, p retreated population hut lacks significant clinical activity as a single ag ent.