Phase II evaluation of docetaxel plus exisulind in patients with androgen independent prostate carcinoma.
OBJECTIVE
In this phase II study, the combination of docetaxel and exisulind (a GMP phosphodiesterase inhibitor) was given to patients with metastatic androgen independent prostate cancer (AIPC) to establish efficacy, assess toxicity, and determine pharmacokinetics of docetaxel administered alone and in combination with exisulind.


METHODS
Fourteen patients with metastatic AIPC were registered to receive weekly docetaxel for 4 weeks, followed by 2 weeks of rest; repeated up to a maximum of 6 cycles. Exisulind 250 mg was given orally twice a day starting on day 8 of the study and taken continuously.


RESULTS
All patients were evaluable for toxicity, response and survival. Grade 3 reversible toxicities included: fatigue, nausea, diarrhea, abdominal pain, rash, syncope, pulmonary edema, deep vein thrombosis, congestive heart failure, and elevations in transaminases, requiring therapy delays and/or dose reductions, or removal from therapy. Only 3 out of 14 patients (21.4%) had a 50% decline in prostate specific antigen (PSA) level that lasted > or =4 weeks; 1 out of 14 patients (7%) had a lymph node response. Median survival was 17.28 months. Docetaxel pharmacokinetics for 11 patients demonstrated mean +/- SD clearance values that were similar during week 1 and week 3 when exisulind had been added.


CONCLUSIONS
: Overall, our trial indicated that the toxicity profile and efficacy of this regimen is unlikely to be substantially better than single agent docetaxel.
Sinibaldi
Victoria J
VJ
Prostate Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. sinibvi@jhmi.edu
Elza-Brown
Kathy
K
Schmidt
Jill
J
Eisenberger
Mario A
MA
Rosenbaum
Eli
E
Denmeade
Samuel R
SR
Pili
Roberto
R
Walczak
Janet
J
Baker
Sharyn D
SD
Zahurak
Marianna
M
Carducci
Michael A
MA
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics
D043823:Taxoids; D000077143:Docetaxel; D013467:Sulindac; C025463:sulindac sulfone