Dose-finding study of weekly docetaxel plus estramustine in patients with hormone-refractory metastatic prostate cancer

Objective: The aim of this phase I study was to find the maximum tolerated dose of weekly docetaxel in association with estramustine in hormone-refractory prostate cancer. Methods: Eleven patients with hormone-refractory prostate cancer were treated with escalating weekly doses of docetaxel (level I, 3 patients, 30 mg/m²; level II, 3 patients, 35 mg/m², level III, 3 patients, 40 mg/m²; level IV, 2 patients, 45 mg/m²) associated with fixed dosage of estramuscine (840 mg/day). Results: In level I, there was only one episode of grade 3 neutropenia; grade 1 nausea and vomiting were registered in 1 patient; in 1 patient mild edema of the lower limbs was noted. In level II, grade 2 stomatitis and grade 1 sensory symptoms occurred in 1 patient, and grade 1 edema in 1 case. In level III, grade 2 edema was noted in 2 patients, damage to nails in 1 patient, asthenia in 1 patient, grade 1 neuropathy in 2 patients, and grade 1 nausea in 1 patient. In level IV, grade 2 edema was present in 1 patient, grade 3 edema in 1 patient, changes with fall of nails and grade 2 erythema of face in 2 patients, asthenia in 2 patients, grade 1 neuropathy in both patients. Nine patients had a more than a 50% decrease in PSA after 2 cycles of therapy. Conclusions: The results of the study suggest a good tolerability of weekly 35 mg/m² dpcetaxel in hormone-refractory prostate cancer in association with estramustine.