Gemcitabine-cisplatin could be clinically useful in metastatic breast cancer

NEW YORK (Reuters Health) - The combination of gemcitabine and cisplatin is active against metastatic breast cancer, whether prior treatment has been minimal or aggressive, according to two phase 2 studies published online on March 23 by the Journal of Clinical Oncology.

The parallel studies, designed by the California Cancer Consortium and Loyola University Chicago and led by Dr. Helen K. Chew at the University of California Davis, Sacramento, enrolled 136 patients with histologically confirmed metastatic or locally recurrent breast cancer. Their median age was 46 years.

One of the two study populations comprised 74 women who had been heavily pretreated, with at least two chemotherapy regimens for metastatic disease or disease progression after bone marrow or hematopoietic cell transplantation. In addition, all had received anthracycline or taxane therapy.

The 62 women in the minimally treated population had received no more than one prior regimen, without either cisplatin or gemcitabine.

Treatment during the study was a 21-day cycle with cisplatin 25 mg/m� daily on days 1 through 4 and gemcitabine 1,000 mg/m� on days 2 and 8. Participants in the heavily pretreated group received a median of three cycles of protocol therapy, while those in the minimally pretreated group received a median of four.

The overall response rate was 26% in both groups. The duration of response was 5.3 months in the heavily pretreated group and 5.9 months in the minimally pretreated. Median overall survival was 10.8 months in the heavily pretreated group and 13.1 months in the minimally pretreated.

In a subset of 55 patients, the study also analyzed polymorphisms in 10 genes relevant to gemcitabine and cisplatin, including those involved in DNA repair, drug metabolism and cell-cycle control.

The XPD-751 polymorphism was associated with significantly increased overall survival, among participants who carried the Lys allele rather than the Gln allele.

The XRCC3 polymorphism was associated with significantly better response rate and progression-free survival among patients who carried the Thr/Thr genotype instead of the heterozygous Met/Thr genotype.

"Our findings," the researchers write, "implicate the potential importance of DNA repair enzymes and drug metabolism enzymes in the prediction of clinical outcome to chemotherapy in metastatic breast cancer."

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