OOPS, Here

Breast Cancer
Nicholas J. Robert, M.D., U.S. Oncology Breast Committee, Fairfax, Va.: In treating advanced breast cancer patients, we try to build on experience in other solid tumors where combinations of paclitaxel and carboplatin are familiar treatments. We've found this combination to be active, well-tolerated, with no cardiotoxicity and good response rates. When looking at women who were Her2 positive, we wanted to see if carboplatin added to the effect of Herceptin and if the combination produced improved outcomes. A phase III study of triplet therapy of carboplatin, docetaxel and Herceptin showed a 64 percent response rate and time to progression of 17 months, which is 10 months better than other combinations.

In a Phase III trial of carboplatin, paclitaxel, and Herceptin presented at the San Antonio Breast Conference in December 2002, Robert found that the triplet of Herceptin, paclitaxel and carboplatin versus the doublet of Herceptin plus paclitaxel was clearly superior with a 52% versus 36% response rate and a 11.2 month versus 6.9 month time to progression, both significant differences. Additionally, adverse event profiles were found to be comparable between the two groups with the exception of more neutropenia and thrombocytopenia in the triplet group.

Mark Pegram, M.D., UCLA School of Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, Calif.: We've looked at various drugs in breast cancer patients who overexpress the Her2 protein (who are thus commonly referred to as being Her2 positive). We found that although the drug of choice for treating Her2 positive patients is the molecularly targeted drug Herceptin, when testing the efficacy of a doublet, the synergy between it and a class of drugs called anthracyclines increased the risk of cardiomyopathy. So we then looked at docetaxel and Herceptin, which was a better choice of taxanes than paclitaxel. It turns out that taxanes such as docetaxel or paclitaxel induce apoptosis (cell death) that augments the benefit of Herceptin. We also have some evidence that the triplet of taxotere (another taxane) plus a platinum drug plus herceptin shows efficacy. We are testing this hypothesis in a randomized clinical trial and the early results look promising.