TY - JOUR
T1 - Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer
AU - Hudes, Gary R.
AU - Greenberg, Richard E.
AU - Krigel, Robert L.
AU - Fox, S.
AU - Scher, Richard M.
AU - Litwin, Samuel
AU - Watts, Perry
AU - Speicher, L
AU - Tew, Kenneth D.
AU - Comis, Robert L.
PY - 1992
Y1 - 1992
N2 - Purpose: Estramustine phosphate (EMP) and vinblastine are two microtubule inhibitors with distinct molecular targets and at least additive antimicrotubule effects in vitro. Their modest single-agent activities in hormone-refractory prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted a phase II trial in hormone-refractory prostate cancer. Patients and Methods: Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1 to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses were repeated every 8 weeks. Response assessment was based on a change in serum prostate-specific antigen (PSA) levels and was correlated with change in pain scores. Results: PSA decreased from baseline by at least 50% in 22 patients (61.1%) and by ≥ 75% in eight patients (22.2%). A 50% or more decrease in PSA on three successive 2-week measurements together with an improved or stable pain score, performance status, and measurable soft tissue disease (if present) was required for a partial response (PR), which occurred in 11 patients for an overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In seven patients with measurable nonosseous disease, there was one PR (14%) and one minor response (MR). In 28 patients with assessable pain, major pain responses occurred in 12 (42.9%). PSA response (≥ 50% decrease times three measurements) was predictive of major pain response with a 93.7% specificity, a 50% sensitivity, and a positive predictive value of 85.7%. Conclusion: We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.
AB - Purpose: Estramustine phosphate (EMP) and vinblastine are two microtubule inhibitors with distinct molecular targets and at least additive antimicrotubule effects in vitro. Their modest single-agent activities in hormone-refractory prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted a phase II trial in hormone-refractory prostate cancer. Patients and Methods: Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1 to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses were repeated every 8 weeks. Response assessment was based on a change in serum prostate-specific antigen (PSA) levels and was correlated with change in pain scores. Results: PSA decreased from baseline by at least 50% in 22 patients (61.1%) and by ≥ 75% in eight patients (22.2%). A 50% or more decrease in PSA on three successive 2-week measurements together with an improved or stable pain score, performance status, and measurable soft tissue disease (if present) was required for a partial response (PR), which occurred in 11 patients for an overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In seven patients with measurable nonosseous disease, there was one PR (14%) and one minor response (MR). In 28 patients with assessable pain, major pain responses occurred in 12 (42.9%). PSA response (≥ 50% decrease times three measurements) was predictive of major pain response with a 93.7% specificity, a 50% sensitivity, and a positive predictive value of 85.7%. Conclusion: We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols/pharmacology
KW - Drug Resistance
KW - Estramustine/administration & dosage
KW - Gonadal Steroid Hormones/therapeutic use
KW - Humans
KW - Male
KW - Microtubules/drug effects
KW - Middle Aged
KW - Pain Measurement
KW - Prostate-Specific Antigen/blood
KW - Prostatic Neoplasms/blood
KW - Survival Analysis
KW - Vinblastine/administration & dosage
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UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:A1992JV90000014&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1200/JCO.1992.10.11.1754
DO - 10.1200/JCO.1992.10.11.1754
M3 - Article
C2 - 1383436
SN - 0732-183X
VL - 10
SP - 1754
EP - 1761
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -