Combination of docetaxel, estramustine phosphate, and zoledronic acid in androgen-independent metastatic prostate cancer: efficacy, safety, and clinical benefit assessment.
OBJECTIVE
Docetaxel is an effective agent for the treatment of androgen-independent prostate cancer (AIPC). Its combination with estramustine phosphate (EMP) has shown promising results in AIPC but the toxicity remains considerable. In an effort to minimize toxicity, we designed an every-2-week docetaxel administration regimen with a 3-day low-dose EMP regimen. Patients with bone metastases also received zoledronic acid.


METHODS
A total of 54 patients with AIPC received docetaxel at 45 mg/m2 and EMP (140 mg orally every 8 hours for nine doses) every 2 weeks. Zoledronic acid was administered at 4 mg every 28 days.


RESULTS
Of the 49 assessable patients, 22 (45%, 95% confidence interval [CI] 31% to 60%) had a prostate-specific antigen response. Of 24 patients with measurable disease, 9 (38%, 95% CI 19% to 59%) had a response to therapy (one complete response and eight partial responses). The median time to progression was 4.4 months (95% CI 2.7 to 6), and overall survival was 13.3 months (95% CI 9 to 17.6). Toxicity was mild, with only 5 cases of grade 3 or 4 toxicity. The pain score improved by 1 point in 21 (54%) of 39 symptomatic patients, and 14 (40%) of 38 patients who used analgesics discontinued analgesic consumption by the end of treatment.


CONCLUSIONS
The combination of an every-2-week regimen of docetaxel, EMP, and zoledronic acid is an effective, well-tolerated regimen that results in symptomatic improvement in a significant proportion of patients with AIPC.
Efstathiou
E
E
Department of Clinical Therapeutics, University of Athens School of Medicine, Haidari, Athens, Greece.
Bozas
G
G
Kostakopoulos
A
A
Kastritis
E
E
Deliveliotis
C
C
Antoniou
N
N
Skarlos
D
D
Papadimitriou
C
C
Dimopoulos
M A
MA
Bamias
A
A
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D015993:Life Tables; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D009503:Neutropenia / Q000139:chemically induced; D009919:Orchiectomy; D010146:Pain / Q000188:drug therapy; D010166:Palliative Care; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D011882:Radiotherapy, High-Energy; D012074:Remission Induction; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007093:Imidazoles; D009363:Neoplasm Proteins; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen