Phase II trial of alternating weekly chemohormonal therapy for patients with androgen-independent prostate cancer.
Two distinct regimens of weekly chemotherapy for hormone-refractory prostate cancer were combined in an alternating schedule and tested in a Phase II trial to determine efficacy and toxic effects. Forty-six patients with hormone-refractory prostate cancer and rising prostate-specific antigen (PSA) levels entered the trial. Therapy consisted of doxorubicin (20 mg/m2/week) plus oral ketoconazole (400 mg three times a day) given at weeks 1, 3, and 5 and vinblastine (5 mg/m2/week) plus oral estramustine (140 mg three times a day) given at weeks 2, 4, and 6. No therapy was given at weeks 7 and 8. Replacement doses of hydrocortisone were administered throughout treatment to counteract potential adrenal insufficiency secondary to the ketoconazole. In 67% of patients (31 of 46), the PSA declined by 50% or greater for a minimum duration of 8 weeks (95% confidence interval, 52-80%). Among the 16 patients with measurable soft tissue disease, there were 12 responses (75%; 95% confidence interval, 47-92%). The median duration of response was 8. 4 months (1.8-14.9). The median survival for the entire group was 19 months. The median survival of PSA responders has not been reached, whereas that of nonresponders was 13 months (P = 0.010). Seventy-six percent of symptomatic patients noted improvement. Hematological toxicity was modest and was managed without growth factors. Peripheral edema (49%) and deep venous thrombosis (18%) were the most common nonhematological toxicities. The alternating weekly regimen of chemohormonal therapy is active for hormone-refractory prostate cancer, providing a high rate of symptom control, soft tissue response, and PSA decline.
Ellerhorst
J A
JA
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Tu
S M
SM
Amato
R J
RJ
Finn
L
L
Millikan
R E
RE
Pagliaro
L C
LC
Jackson
A
A
Logothetis
C J
CJ
D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D001842:Bone and Bones / Q000000981:diagnostic imaging; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000627:therapeutic use*; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011877:Radionuclide Imaging; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D000893:Anti-Inflammatory Agents; D004961:Estramustine; D014747:Vinblastine; D004317:Doxorubicin; D017430:Prostate-Specific Antigen; D007654:Ketoconazole; D006854:Hydrocortisone