NEW YORK (Reuters Health) - In patients with metastatic triple-negative breast cancer, cisplatin plus gemcitabine appears to be an effective option, Chinese researchers say.
As Dr. Xi-Chun Hu told Reuters Health by email, "The cisplatin plus gemcitabine regimen, already fully-assessed in other malignancies, is an alternative or even preferential first-line doublet chemotherapy strategy for patients with metastatic triple negative breast cancer."
As reported March 17th online in The Lancet Oncology, Dr. Hu of Shanghai Medical College, Fudan University and colleagues randomly assigned 236 patients with previously untreated, histologically confirmed metastatic triple-negative breast cancer to receive either cisplatin plus gemcitabine or paclitaxel plus gemcitabine IV every 3 weeks for a maximum of eight cycles.
After a median follow-up of about 16 months, the hazard ratio for progression-free survival in the cisplatin plus gemcitabine group was 0.692. Median progression-free survival was 7.73 months compared to 6.47 months in the paclitaxel plus gemcitabine group.
Both regimens were well tolerated although they had different toxicity profiles. For example, in terms of grade 3 or 4 adverse events, nausea was seen in 7% of the cisplatin plus gemcitabine group vs <1 3="" also="" and="" case="" for="" gemcitabine="" group.="" of="" p="" paclitaxel="" plus="" the="" this="" thrombocytopenia="" vomiting="" vs="" was="">
However, the cisplatin plus gemcitabine group had significantly fewer grade 1-4 alopecia events (10% vs 36%) and less peripheral neuropathy (23% vs 51%), but more grade 1-4 anorexia (28% vs 8%).
"Future work," the investigators conclude, "could include a validation of our cisplatin plus gemcitabine regimen in non-Asian populations and the identification of predictive markers for treatment with platinum-based regimens" in such patients.
In an editorial, Dr. Lisa Carey of University of North Carolina, Chapel Hill notes that "only eight cycles (about 6 months) of protocol-directed therapy were allowed, and therefore the effect of ongoing therapy cannot yet be assessed."
However, she concludes, the study "provides evidence for the establishment of an effective, non-anthracycline and non-taxane combination regimen for patients with triple-negative breast cancer, and further evidence of the activity of platinum therapy in this patient subset."
Commenting by email, oncologist Dr. Sherene Loi of the University of Melbourne, Australia told Reuters Health that the investigators "should be commended for carrying out this randomized trial, though the inclusion of a third arm of single agent weekly paclitaxel would have perhaps answered more questions regarding single versus doublet chemo combinations as well as dosing regimen."
"International guidelines recommend the use of sequential single agent chemotherapy except in situations where there is significant and life threatening visceral metastases or the need for rapid symptom control . . . as doublets have increased toxicity and do not seem to have improvements in overall survival," she said. "Whilst this combination did show improvement in PFS, no overall survival advantage is seen."
"No biological correlative analysis was presented in this data," Dr. Loi continued. "It could be interesting to know the BRCA mutation status of these patients, particularly given that the median age of the study participants was less than 50 years. Recent data suggests that nearly 15% of these patients could carry gene mutation even without a family history."
"Finally," Dr. Loi said, "I personally think we need to move away from empirical chemotherapy combinations and towards approaches with molecular-based rationale. All future trials should have extensive correlative tissue collection (trials in triple-negative breast cancer now absolutely need to have germline BRCA mutation information) as this may help us answer current and future biological questions on who benefits the most from the investigational agents that were evaluated."
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