Results of a phase II study using estramustine phosphate and vinblastine in combination with high-dose three-dimensional conformal radiotherapy for patients with locally advanced prostate cancer

Purpose: To assess the feasibility and tolerance of neoadjuvant and concomi tant estramustine phosphate and vinblastine (EV) with high-dose three-dimen sional conformal radiotherapy (3D-CRT) for patients with unfavorable-risk p rostate cancer. Patients and Methods: Twenty-seven patients with unfavorable-risk prostate cancer were enrolled onto a prospective study to determine the feasibility of combining EV with 3D-CRT. Patients were eligible if any of the following requirements were satisfied: (1) Gleason score greater than or equal to 8 and prostate-specific antigen (PSA) > 10 ng/mL; (2) Gleason score of 7 and PSA > 20 ng/mL; (3) clinical stage T3N0M0 disease with PSA > 20 ng/mL; (4) any patient with T4N0M0 disease; or (5) patients with TXN1MO disease. Thera py consisted of three 8-week cycles of EV and 8 weeks of 3D-CRT. Estramusti ne phosphate was given orally beginning on week 1 and continued until the c ompletion of 3D-CRT. Each 8-week cycle of vinblastine consisted of 6 weekly intravenous injections followed by a 2-week rest period. Radiation therapy wets administered using a three-dimensional conformal approach to a prescr iption dose of 75.6 Gy. The median follow-vp was 26 months (range, 6 to 40 months). Results: Twenty-three (85%) of 27 patients completed the entire course of t herapy and were assessable for toxicities and biochemical outcome. Two pati ents (7%) developed grade 3 hematologic toxicity that resolved, and two pat ients (7%) developed grade 3 hepatoxicity, manifesting as persistent elevat ion of serum transaminase levels, necessitating discontinuation of the chem otherapy and withdrawal from the treatment program. The most prominent adve rse effects from this regimen were mild to moderate (grade 1 to 2) nausea a nd fatigue related to estramustine. Mild peripheral edema was seen in 15% o f patients and was treated with diuresis. 3D-CRT was tolerated well in thes e patients. Medications were required for relief of acute grade 2 rectal (g astrointestinal [GI]) and urinary (genitourinary [GU]) symptoms in 35% and 48% of patients, respectively. Three patients developed acute grade 3 GU to xicities. The 2-year actuarial likelihood of late grade 2 GI toxicity was 2 0%. No late grade 3 or 4 GI toxicities were observed. The 2-year actuarial likelihoods of late grade 2 and 3 GU toxicities were 25% and 12%, respectiv ely. No grade 4 GO toxicity was observed. Conclusion: Neoadjuvant and concomitant EV with high-dose 3D-CRT is well to lerated in patients with unfavorable-risk prostate cancer. Although the inc idence of modest (grade 2) late GI and GU toxicities seem to be increased c ompared with 3D-CRT alone or in combination with androgen ablation therapy, no severe toxicities were encountered with this regimen. (C) 2000 by Ameri can Society of Clinical Oncology.