Table of Contents
ISRN Oncology
Volume 2012, Article ID 176789, 8 pages
http://dx.doi.org/10.5402/2012/176789
Clinical Study

Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial

1Department of Oncology, Oslo University Hospital, 0424 Oslo, Norway
2Faculty of Medicine, University of Oslo, Oslo, Norway
3Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway
4AstraZeneca, R&D, Mereside Alderley Park, Macclesfield, UK

Received 24 January 2012; Accepted 29 February 2012

Academic Editors: A. M. Garcia-Lora and C. Nicco

Copyright © 2012 Olav Engebraaten et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In patients with metastatic breast cancer, taxane treatment demonstrates activity but is not curative. Targeted treatment modalities are therefore necessary in order to improve outcomes in this group. A randomized placebo-controlled phase II trial was initiated to evaluate effect and toxicity of gefitinib (250 mg QD) and docetaxel 35 mg/m2 (six of seven weeks) (NCT 00319618). The inclusion of 66 patients was planned. The study was closed due to treatment-related toxicity. Of the 18 included patients, seven (of which three received gefitinib) were withdrawn from the study due to toxicity. Of the nine patients receiving gefitinib and chemotherapy, one achieved a partial response and four stable disease. In the chemotherapy of nine patients, four had a partial response and four stable disease. The breast cancer patients in this study were genotyped using a panel of 14 single-nucleotide polymorphisms (SNPs), previously found associated with docetaxel clearance in a cohort of lung cancer patients. We were unable to identify genes related to toxicity in this study. Nevertheless, toxicity was aggravated by the addition of the tyrosine kinase inhibitor. In conclusion, despite adequately tolerated as monotherapy, combination regimens should be carefully considered for overlapping adverse events in order to avoid increased treatment-related toxicity.