A phase IB study of ABT-751 in combination with docetaxel in patients with advanced castration-resistant prostate cancer.
BACKGROUND
This study investigated the safety, pharmacokinetics (PK) and clinical antitumor activity of ABT-751, a novel sulfonamide antimitotic and vascular disrupting agent, in combination with docetaxel (Taxotere) in patients with castration-resistant prostate cancer (CRPC).


METHODS
Patients received docetaxel (60-75 mg/m(2)) i.v. on day 1 and ABT-751 (100-200 mg) orally daily for 14 days, repeated every 3 weeks for up to 10 times on four escalating dose levels (DLs).


RESULTS
Thirty-two patients received a median of 8.5 treatment cycles (range 1-10). One of six patients on DL 3 (D 60 mg/m(2) + A 200 mg) and 4 (D 75 mg/m(2) + A 200 mg) experienced dose-limiting toxicity, and both DLs were expanded. Overall, severe adverse events occurred more commonly on DL 4 than 3 (47% versus 18% of patients). PK data for docetaxel and ABT-751 were similar to reported literature. Best post-treatment prostate-specific antigen decline of > or =50% occurred in 60% and objective responses occurred in 45% of patients. Median overall survival was 24 months (95% confidence interval 8.3-37.7 months).


CONCLUSIONS
The combination of ABT-751 and docetaxel is safe and active in CRPC. Based on the cumulative safety analysis, the recommended phase II dose of ABT-751 is 200 mg daily with docetaxel 60 mg/m(2) for this patient population.
Michels
J
J
Department of Medical Oncology, Vancouver Centre, British Columbia Cancer Agency, Vancouver; Department of Medical Oncology, Vancouver Island Centre, British Columbia Cancer Agency, Victoria.
Ellard
S L
SL
Department of Medical Oncology, Southern Interior Centre, British Columbia Cancer Agency, Kelowna.
Le
L
L
Department of Medical Oncology, Fraser Valley Centre, British Columbia Cancer Agency, Surrey.
Kollmannsberger
C
C
Department of Medical Oncology, Vancouver Centre, British Columbia Cancer Agency, Vancouver.
Murray
N
N
Department of Medical Oncology, Vancouver Centre, British Columbia Cancer Agency, Vancouver.
Tomlinson Guns
E S
ES
The Prostate Centre at Vancouver General Hospital, Vancouver, British Columbia, Canada.
Carr
R
R
Abbott Laboratories, Abbott Park, IL, USA.
Chi
K N
KN
Department of Medical Oncology, Vancouver Centre, British Columbia Cancer Agency, Vancouver. Electronic address: k.chi@bccancer.bc.ca.
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002369:Castration; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome
C490492:ABT751; D013449:Sulfonamides; D043823:Taxoids; D000077143:Docetaxel