Wednesday, April 27, 2011

New Drug Combo for Metastatic Disease


An early-phase study showed that the new taxoid, cabazitaxel (XRP6258), is not only safe but has significant activity when combined with capecitabine in patients with metastatic breast cancer previously treated with paclitaxel-like agents. This is a new drug combo with great promise that women who have Stage 4 disease can use in their arsenal against their cancer.


Eur J Cancer. 2011 May 1;47(7):1037-1045, C Villanueva, A Awada, M Campone, JP Machiels, T Besse, E Magherini, F Dubin, D Semiond, X Pivot

 

Abstract

Background: Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in patients with MBC who had been previously treated with taxanes and anthracyclines.

Patients and Methods: In part I, we used a 3 + 3 dose–escalation scheme to assess the MTD of intravenous cabazitaxel (day 1) with oral capecitabine twice daily (days 1–14) every 3 weeks. In part II, we evaluated the objective response rate (ORR) at the MTD.

Results: Thirty-three patients were enrolled and treated (15 in part I; 18 in part II). Cabazitaxel 20 mg/m2 plus capecitabine 1000 mg/m2 was the MTD. Pharmacokinetic analysis showed no apparent drug–drug interaction. In all patients, the main grade 3–4 toxicities were asthenia (n = 5), hand–foot syndrome (n = 5), neutropenia (n = 21), neutropenic infection (n = 1), and neutropenic colitis (n = 1). One patient had febrile neutropenia. Antitumour activity was observed at all dose-levels with two complete responses, five partial responses (PRs), and 20 disease stabilisations (seven unconfirmed PR). At the MTD, 21 patients were evaluable for efficacy. The ORR was 23.8% (95% CI: 8.2–47.2%). The median response duration was 3.1 months (95% CI: 2.1–8.4 months), with four of five lasting for more than 3 months. Median time to progression was 4.9 months.

Conclusions: Cabazitaxel combined with capecitabine is active, has a safety profile consistent with a taxane plus capecitabine combination and warrants further investigation in patients with MBC.

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