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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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/m2 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/m2), 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/m2 q3weeks, respectively. The combination is tolerable and has potential antitumor activity.

Original languageEnglish
Pages (from-to)1800-1805
Number of pages6
JournalCancer Biology and Therapy
Issue number19
StatePublished - 10 Oct 2009
Externally publishedYes


  • Carboxyamidotriazole
  • Clinical trial
  • Ovarian cancer
  • Paclitaxel
  • Pharmacokinetics


Dive into the research topics of 'A phase I study of paclitaxel and continuous daily CAI in patients with refractory solid tumors'. Together they form a unique fingerprint.

Cite this