A pharmacokinetically guided Phase II study of carboxyamido-triazole in androgen-independent prostate cancer

Kenneth S. Bauer, William D. Figg*, J. Michael Hamilton, Elizabeth C. Jones, Ahalya Premkumar, Seth M. Steinberg, Valerie Dyer, W. Marsten Linehan, James M. Pluda, Eddie Reed

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


We conducted a Phase II clinical trial of the antiproliferative, antimetastatic, and antiangiogenic agent carboxyamido-triazole (CAI), using pharmacokinetic assessment to guide drug dosing. Fifteen patients who had stage D2 androgen-independent prostate cancer with soft tissue metastases were enrolled. Because CAI previously had been shown to decrease prostate- specific antigen secretion in vitro, this marker was not used to assess disease status. The dose of CAI used in this study was calculated so that plasma steady-state maximum concentrations between 2.0 and 5.0 μg/ml would be maintained. Following the initial dosage adjustment, 93% (14 of 15) of patients were within the predicted range. Fourteen of 15 patients were evaluable for response. All of the 14 evaluable patients demonstrated progressive disease at ~2 months. Twelve patients progressed by computed tomography and or bone scan at 2 months, whereas two patients demonstrated clinical progression at 1.5 and 2 months. One patient was removed from study at 6 weeks due to grade II peripheral neuropathy lasting >1 month. Although no clinical responses were noted, a 27.7% decrease in serum vascular endothelial growth factor concentration was observed. CAI does not possess clinical activity in patients with androgen-independent prostate cancer and soft tissue metastases. Pharmacokinetically guided dosing, although found to be feasible using a Bayesian approach, was not found to be of practical benefit. Although plasma CAT concentrations were maintained within the designated range, grade III toxicity requiring drug discontinuation was still observed.

Original languageEnglish
Pages (from-to)2324-2329
Number of pages6
JournalClinical Cancer Research
Issue number9
StatePublished - Sep 1999
Externally publishedYes


Dive into the research topics of 'A pharmacokinetically guided Phase II study of carboxyamido-triazole in androgen-independent prostate cancer'. Together they form a unique fingerprint.

Cite this