Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC).
Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.
Kattan
Joseph G
JG
Hôtel-Dieu de France University Hospital, Beirut, Lebanon. jkattan62@hotmail.com
Farhat
Fady S
FS
Chahine
Georges Y
GY
Nasr
Fady L
FL
Moukadem
Walid T
WT
Younes
Fariha C
FC
Yazbeck
Nadine J
NJ
Ghosn
Marwan G
MG
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen