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Clinical Trial
. 2009 Oct;8(19):1800-5.
doi: 10.4161/cbt.8.19.9593.

A phase I study of paclitaxel and continuous daily CAI in patients with refractory solid tumors

Nilofer Azad  1 , Alyssa Perroy, Erin Gardner, Chiyo K Imamura, Cynthia Graves, Gisele A Sarosy, Lori Minasian, Herbert Kotz, Miranda Raggio, William D Figg, Elise C Kohn
Affiliations
Clinical Trial

A phase I study of paclitaxel and continuous daily CAI in patients with refractory solid tumors

Nilofer Azad et al. Cancer Biol Ther. 2009 Oct.

Abstract

Background: Carboxyamido-triazole (CAI) is a calcium influx inhibitor with anti-angiogenic and anti-invasive properties and stabilizes tumor progression in patients. We hypothesized daily oral micronized CAI with q3 week paclitaxel would be well-tolerated and active.

Results: Twenty-nine heavily pretreated patients [median 3 [0-7]] were enrolled on five dose levels. No additive or cumulative toxicity was observed, and grade III nonhematological toxicity was rare. Neutropenia was the most common hematologic toxicity, seen in 79% of patients, with a trend towards increasing grade with higher paclitaxel doses. The recommended phase II dose defined by the maximum tolerated dose (MTD) was CAI 250 mg daily and paclitaxel 200 mg/m(2) q3weeks. Pharmacokinetic analysis revealed paclitaxel increases CAI trough concentration at all dose levels by over 100% (p < 0.0001). A trend towards higher steady-state CAI trough concentrations was found in patients with a partial response (PR; p = 0.09). Six patients had confirmed PR (24%; 4-67 cycles, median 10); two patients had minor responses.

Patients and methods: Eligible patients with solid tumors received micronized CAI daily (150-250 mg PO) and paclitaxel intravenously q3weeks (175-250 mg/m(2)), sequentially escalating each drug. CAI preceded paclitaxel by one week to permit pharmacokinetic analysis. Patients were assessed for toxicity, pharmacokinetics and disease outcome.

Conclusions: The MTD of the combination of CAI and paclitaxel is 250 mg daily and 200 mg/m(2) q3weeks, respectively. The combination is tolerable and has potential antitumor activity.

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