Taxotere Carboplatin Herceptin as adjuvant therapy for breast cancer – pro

There are now 4 major trials demonstrating improved disease-free survival with the addition of trastuzumab in the adjuvant setting. NSABP [National Surgical Adjuvant Breast and Bowel Project], was the simplest one: doxorubicin and cyclosphosphamide (AC) followed by paclitaxel, all given conventionally with or without trastuzumab. A very similar trial, the Intergroup 9831 trial led by the North Central Group, looked at essentially the same thing, AC-paclitaxel, the only wrinkle being that it used low-dose weekly paclitaxel rather than conventional high-dose paclitaxel given every 3 weeks. It also included a novel third arm in which trastuzumab was not given with the paclitaxel but was delayed until the end of chemotherapy. The fourth of these large trials was HERA [Herceptin Adjuvant]In HERA, a minimal chemotherapy regimen equal to 4 cycles of AC was required, and all therapy, including radiation, had to be completed before patients received trastuzumab. In that trial, patients received 0, 1, or 2 years of trastuzumab after adjuvant chemotherapy. The last trial was the BCIRG [Breast Cancer International Research Group] 006 trial, which substituted docetaxel in place of paclitaxel, and included a novel third arm that used carboplatin and docetaxel with trastuzumab and omitted the anthracycline. In the BCIRG trial, the carboplatin, docetaxel, and trastuzumab arm improved outcome compared with the control arm, but it is possible that it was less effective than the AC-docetaxel/trastuzumab arm. That comparison is underpowered at present. NCCN lists this regimen, TCH, as an option.

Is TCH standard? Experts are divided. The general consensus is that it may be an appropriate regimen when anthracyclines cannot be used or when a patient, with all factors considered agrees to a non-antracycline containing regimen.

Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673-1684.

Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC –> T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC –> TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat. 2005;94(suppl1):S5.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.

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