, Volume 68, Issue 6, pp 1565-1573
Date: 06 May 2011

Tesetaxel, a new oral taxane, in combination with capecitabine: a phase I, dose-escalation study in patients with advanced solid tumors

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Abstract

Purpose

This phase I study was conducted primarily to determine the maximum tolerated dose (MTD) of tesetaxel, a novel, orally active, semisynthetic microtubule inhibitor of the taxane class, administered with oral capecitabine to patients with advanced solid tumors.

Methods

During each 21-day cycle, patients were to receive tesetaxel on Day 1 and capecitabine twice daily on Days 1 through 14. The starting dose was tesetaxel 18 mg/m2 and capecitabine 1,250 mg/m2/day. These doses were increased based on tolerability during the first cycle according to the protocol-specified dose-escalation scheme. Response was evaluated every other treatment cycle according to RECIST. Serial blood samples were collected during the first and second cycles to explore possible pharmacokinetic drug interactions.

Results

Twenty-seven patients were enrolled and treated. The most frequently reported dose-limiting toxicities were neutropenia and febrile neutropenia, with individual patients experiencing dose-limiting stomatitis and diarrhea. The MTD for the treatment regimen was defined as tesetaxel 27 mg/m2 and capecitabine 2,500 mg/m2/day. The most common ≥Grade 3 treatment-related adverse events included leukopenia (44% of patients) and neutropenia (41%). Of 22 evaluable patients, the best overall response was stable disease in 82% and progressive disease in 18%. No meaningful pharmacokinetic drug interactions were apparent.

Conclusions

The results of this study demonstrate that these two orally active agents can be combined at the individual MTD of each drug with acceptable toxicity. These data further support the continued clinical development of tesetaxel both as a single agent and in combination with other active cancer therapeutics.

Preliminary data were presented in abstract form at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO), May 13–17, 2005, Orlando, FL and the 42nd Annual Meeting of ASCO, June 2–6, 2006, Atlanta, GA. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=34&abstractID=32680 and http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=40&abstractID=34424.