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 prostrate cancer Journal Article

Authors: Zelefsky, M. J.; Kelly, W. K.; Scher, H. I.; Lee, H.; Smart, T.; Metz, E.; Schwartz, L.; Fuks, Z.; Leibel, S. A.
Article Title: 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 prostrate cancer
Abstract: Purpose: To assess the feasibility and tolerance of neoadjuvant and concomitant estramustine phosphate and vinblastine (EV) with high-dose three- dimensional conformal radiotherapy (3D-CRT) for patients with unfavorable- risk prostate cancer. Patients and Methods: Twenty-seven patients with unfavorable-risk prostate cancer were entailed 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 ≥ 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. Therapy consisted of three 8-week cycles of EV and 8 weeks of 3D-CRT. Estramustine phosphate was given orally beginning on week 1 and continued until the completion of 3D-CRT. Each 8-week cycle of vinblastine consisted of 6 weekly intravenous injections followed by a 2-week rest period. Radiation therapy was administered using a three-dimensional conformal approach to a prescription dose of 75.6 Gy. The median follow-up was 26 months (range, 6 to 40 months). Results: Twenty-three (85%) of 27 patient's completed the entire course of therapy and were assessable for toxicities and biochemical outcome. Two patients (7%) developed grade 3 hematologic toxicity that re- solved, and two patients (7%) developed grade 3 hepatoxicity, manifesting as persistent elevation of serum transaminase levels, necessitating discontinuation of the chemotherapy and withdrawal from the treatment program. The most prominent adverse effect's from this regimen were mild to moderate (grade 1 to 2) nausea and fatigue related to estramustine. Mild peripheral edema was seen in 15% of patients and was treated with diuresis. 3D-CRT was tolerated well in these patients. Medications were required for relief of acute grade 2 rectal (gastrointestinal [GI]) and urinary (genitourinary [GU]) symptoms in 35% and 48% of patients, respectively. Three patients developed acute grade GU toxicities. The 2-year actuarial likelihood of late grade 2 GI toxicity was 20%. 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%, respectively. No grade 4 GU toxicity was observed. Conclusion: Neoadjuvant and concomitant EV with high-dose 3D-CRT is well tolerated in patients with unfavorable-risk prostate cancer. Although the incidence of modest (grade 2) late GI and GU toxicities seem to be increased compared with 3D-CRT alone or in combination with androgen ablation therapy, no severe toxicities were encountered with this regimen. (C) by American Society of Clinical Oncology.
Keywords: clinical article; treatment outcome; clinical trial; fatigue; cancer combination chemotherapy; cancer radiotherapy; radiation dose; combined modality therapy; neoadjuvant therapy; cancer staging; prospective studies; prostate specific antigen; edema; liver toxicity; phase 2 clinical trial; anemia; etoposide; blood toxicity; nausea; antineoplastic combined chemotherapy protocols; radiotherapy dosage; risk factors; hemoglobin; vinblastine; prostate cancer; prostate-specific antigen; prostatic neoplasms; vindesine; radiotherapy, conformal; aminotransferase; administration, oral; recombinant erythropoietin; injections, intravenous; gastrointestinal diseases; estramustine; male urogenital diseases; estramustine phosphate; humans; human; male; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 18
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2000-05-09
Start Page: 1936
End Page: 1941
Language: English
PUBMED: 10784635
PROVIDER: scopus
Notes: Export Date: 18 November 2015 -- Source: Scopus