Journal Title
Title of Journal: Cancer Chemother Pharmacol
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Abbravation: Cancer Chemotherapy and Pharmacology
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Publisher
Springer-Verlag
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Authors: Bojana Milojkovic Kerklaan Veronique Diéras Christophe Le Tourneau Marja MerguiRoelvink Alwin D R Huitema Hilde Rosing Jos H Beijnen Sandrine Marreaud AnneSophie Govaerts Martine J PiccartGebhart Jan H M Schellens Ahmad Awada
Publish Date: 2012/09/29
Volume: 71, Issue: 1, Pages: 53-62
Abstract
This phase I study was performed to determine the maximum tolerated dose MTD doselimiting toxicities DLT safety profile recommended dose for phase II studies the pharmacokinetics and antitumor activity of the combination of lonafarnib farnesyl transferase inhibitor trastuzumab and paclitaxel in Her2positive advanced breast cancerTwentythree patients with Her2overexpressing breast cancer received in the first cycle paclitaxel and trastuzumab and from cycle 2 onwards lonafarnib which was added to the combination Doselimiting toxicity DLT was determined during the second cycleThe MTD and the recommended dose for phase II trials are lonafarnib 250 mg/day 125 mg/bidaily BID continuously paclitaxel 175 mg/m² 3h infusion every 3 weeks and trastuzumab 4 mg/kg loading dose and 2 mg/kg/week thereafter The most frequently observed adverse events starting from cycle 1 onwards were alopecia myalgia sensory neuropathy fatigue arthralgia leukocytopenia and neutropenia From cycle 2 onwards additional adverse events appeared such as diarrhea nausea dyspepsia vomiting and allergy The mean systemic exposures of both lonafarnib and paclitaxel through all dose levels were higher in the regimen with all three study medications but with no statistically significant difference Preliminary antitumor activity CR + PR was observed in 58 of all patientsLonafarnib can be safely combined and tolerated with full doses of paclitaxel and trastuzumab in Her2positive advanced breast cancer patients Promising preliminary antitumor activity warrants further evaluation of lonafarnib in combination with paclitaxel and trastuzumab in Her2positive breast cancer
Keywords:
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