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Engebraaten O, Edvardsen H, Løkkevik E, et al. Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial. ISRN Oncol. 2012;2012:176789doi: 10.5402/2012/176789.
Engebraaten, O., Edvardsen, H., Løkkevik, E., Naume, B., Kristensen, V., Ottestad, L., & Natarajan, V. (2012). Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial. ISRN oncology, 2012176789. https://doi.org/10.5402/2012/176789
Engebraaten, Olav, et al. "Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial." ISRN oncology vol. 2012 (2012): 176789. doi: https://doi.org/10.5402/2012/176789
Engebraaten O, Edvardsen H, Løkkevik E, Naume B, Kristensen V, Ottestad L, Natarajan V. Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial. ISRN Oncol. 2012;2012:176789. doi: 10.5402/2012/176789. Epub 2012 May 14. PMID: 22666610; PMCID: PMC3361199.
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ISRN Oncol. 2012;2012:176789. doi: 10.5402/2012/176789. Epub 2012 May 14.

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

ISRN oncology

Olav Engebraaten, Hege Edvardsen, Erik Løkkevik, Bjørn Naume, Vessela Kristensen, Lars Ottestad, Vasanti Natarajan

Affiliations

  1. Department of Oncology, Oslo University Hospital, 0424 Oslo, Norway.

PMID: 22666610 PMCID: PMC3361199 DOI: 10.5402/2012/176789

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/m(2) (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 Of the 18 included patients, seven (of which three received gefitinib) were withdrawn from the study due to toxicity.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.

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