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Phase II Study of Dolastatin-10 in Patients with Hormone-refractory Metastatic Prostate Adenocarcinoma¹

Division of Hematology/Oncology, Department of Medicine [U. V., M. H.], and Department of Biostatistics [W. D.], Wayne State University, and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201; University of Colorado Health and Science Center, Denver, Colorado [M. G., A. K.]; Fox Chase Cancer Center, Philadelphia, Pennsylvania [G. H.]; and National Cancer Institute, Bethesda, Maryland [J. W.]

ABSTRACT

Dolastatin-10 is a natural, cytotoxic peptide with microtubule-inhibitory and apoptotic effects. It has demonstrated in vitro and in vivo efficacy in the DU-145 human prostate cancer model. A Phase II clinical trial was designed in patients with hormone-refractory prostate cancer. Dolastatin-10 was administered at a dose of 400 µg/m² i.v. every 3 weeks. Dose escalation to 450 µg/m² was permitted. Toxicity evaluation was conducted every 2 weeks, and assessment of response was done at the end of every two cycles. Sixteen patients were enrolled between October 1998 to December 1999. The median age was 71 years (range, 59–79 years). Median prostate-specific antigen 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-only metastases, and seven had measurable disease with or without bone metastases. 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 µg/m². The major toxicities observed were grade 3 and 4 neutropenia in 8 patients and grade 3 neuropathy in 1 patient. All 15 patients are evaluable for response. Three patients demonstrated stable disease; 2 of these had bone disease, and 1 had nodal metastasis. All others had disease progression. Dolastatin-10 is very well tolerated in this elderly, pretreated population but lacks significant clinical activity as a single agent.

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