Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 11, Pages 2480-2486Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-2610
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Funding
- Polaris Pharmaceuticals
- VA Career Development Award-2
- VA Merit [1I01BX001784]
- NCI Cancer Center Support Grant [P30CA093373-06]
- National Cancer Institute [K12CA138464]
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Purpose: This phase I study examined the toxicity and tolerability of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies. Experimental Design: Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, Zubrod performance status 0-2, and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5 to 36 mg/m(2) and up to 10 doses of docetaxel (75 mg/m(2)) every 3 weeks. Primary endpoints were safety, toxicity, and a recommended phase II dose. Circulating arginine levels were measured before each cycle. Tumor response was measured as a secondary endpoint every 6 weeks on study. Results: Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1st dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3 to 4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with 10 patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including 2 patients with PSA response) were documented, and 7 patients had stable disease. Conclusions: ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted, and expansion cohorts are now accruing for both castrate-resistant prostate cancer and non-small cell lung cancer at a recommended phase II dose of 36 mg/m(2). (C)2015 AACR.
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