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The Oncologist, Vol. 11, No. 5, 533, May 2006; doi:10.1634/theoncologist.11-5-533
© 2006 AlphaMed Press

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Letter to the Editor

Trastuzumab Combined with Paclitaxel after Doxorubicin and Cyclophosphamide for Operable HER2-Positive Breast Cancer

Gianluigi Ferretti, Alessandra Felici, Paola Papaldo, Paolo Carlini, Alessandra Fabi, Francesco Cognetti

Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy

Correspondence: Gianluigi Ferretti, M.D., Ph.D., Department of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. Telephone: 011390652665354; Fax: 011390652665637; e-mail: gia.fer{at}flashnet.it

Received February 1, 2006; accepted for publication March 16, 2006.

Concerning the controversies in the use of trastuzumab for early-stage breast cancer, Cianfrocca and Gradishar [1] have recently reported that an unplanned interim analysis of the North Central Cancer Treatment Group N9831 trial revealed a 36% relative reduction in the risk for recurrence for concurrent compared with sequential trastuzumab (p = .0114) [2], even though further follow-up is needed to ascertain whetherthis trend continues.

Romond et al. [3] have recently presented the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer. The authors conclude that trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. In trial B-31, 805 patients received doxorubicin and cyclophosphamide every 21 days for four cycles followed by paclitaxel every 3 weeks for four cycles plus weekly trastuzumab for 52 weeks; in only 59 patients, paclitaxel was given weekly for 12 weeks. In trial N9831, 808 patients were administered doxorubicin and cyclophosphamide as in trial B-31 but followed by 12 weekly doses of paclitaxel plus weekly trastuzumab for 52 weeks.

It might be highlighted that exposure to lower and more frequent doses of paclitaxel could potentially exploit antiangiogenic and proapoptotic effects [4]. In meta-static breast cancer, weekly administration of paclitaxel has been reported to be superior to once-every-3-weeks administration [5]. As primary systemic chemotherapy, weekly paclitaxel, compared with once-every-3-weeks administration, improved the likelihood of pathologic complete remission [6]. By contrast, Romond et al. [3] assert that there was no evidence that the benefit of trastuzumab differed significantly between the B-31 and N9831 trials. The finding that the same effect of trastuzumab was observed in both the studies deserves further investigation, given the difference in the paclitaxel schedule.


    DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
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The authors indicate no potential conflicts of interest.


    REFERENCES
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  1. Cianfrocca M, Gradishar WJ. Controversies in the therapy of early stage breast cancer. The Oncologist 2005;10:766–779.[Abstract/Free Full Text]
  2. Perez EA, Suman VJ, Davidson N et al. NCCTG 9831: May 2005 update. Presented at the 2005 Annual Meeting of the American Society of Clinical Oncology, Orlando, Florida, May 13–17, 2005.
  3. 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.[Abstract/Free Full Text]
  4. Seidman AD. "Will weekly work"? Seems to be so.... J Clin Oncol 2005;23:5873–5874.[Free Full Text]
  5. Seidman AD, Berry D, Cirrincione C et al. Phase II study of weekly paclitaxel via 1-hour infusion versus standard 3h infusion every third week in the treatment of metastatic breast cancer, with trastuzumab for HER2 positive MBC and randomized for trastuzumab in HER2 normal MBC. Proc Am Soc Clin Oncol 2004;22:6s.
  6. Green MC, Buzdar AU, Smith T et al. Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol 2005;23:5983–5992.[Abstract/Free Full Text]



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