Synergy between Herceptin & 2 chemo drugs valid for HER+ not HER-
In this letter below the authors explain that synergy between Herceptin & chemo drugs is only working if the tumours are HER2 positive.
Note 1: Aside for the reasons already found by researchers for the occasional loss of efficacy or appearence of resistance to Herceptin one may speculate that if the cancer cells become less HER2 positive (as in the case of a reversal to ER+) the loss of effectiveness may be agravated by the loss of synergy. Note 2: This does not necessarily mean that no residual efficacy will remain. As stated by a Glaxo researcher: "By no means are we limiting our development program to only HER2-positive patients," GSK's Stein says. Though the most advanced trials for Tykerb are focused on HER2-positive patients, Stein says there is evidence that the drug could find use in the wider population of breast cancer patients. "Although the response rate was higher in the HER2-positive population, there were responders in the HER2-negative population as well," he notes. Extracted from article at: http://pubs.acs.org/cen/coverstory/84/8432cancer.html ===================== http://theoncologist.alphamedpress.o.../full/11/7/853. Letter to the Editor Adjuvant Trastuzumab with Docetaxel or Vinorelbine for HER-2-Positive Breast Cancer Gianluigi Ferretti, Paola Papaldo, Alessandra Fabi, Paolo Carlini, Alessandra Felici, Francesco Cognetti Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy Correspondence: Gianluigi Ferretti M.D., Ph.D., Division of Medical Oncology A, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy. Telephone: 00390652665354; Fax: 00390652665637; e-mail: gia.fer@flashnet.it </FONT> Received April 13, 2006; accepted for publication May 26, 2006. Colozza et al. [1] recently presented an overview of four adjuvant trials with trastuzumab in patients with HER-2-overexpressing and/or amplified breast cancers (the North Central Cancer Treatment Group Trial N9831, the National Surgical Adjuvant Breast and Bowel Project Trial B31, the Breast Cancer International Research Group Trial 006, and the HERceptin® Adjuvant study). A very recent study showed that a short course of trastuzumab administered concomitantly with docetaxel or vinorelbine is effective in women with breast cancer who have an amplified HER-2/ neu gene [2]. In vitro studies indicated that the combination of trastuzumab and vinorelbine exerts synergistic activity [3]. In fact, the results of recent clinical studies of this combination inuntreated or heavily pretreated patients with HER-2-positive metastatic breast cancer [4, 5] have shown high objective response rates. In vitro, the combination of trastuzumab with docetaxel exerts synergistic activity, as well [2]. This combination in untreated patients with HER-2-positive metastatic breast tumors showed remarkable efficacy [6]. Concerning the adjuvant setting, Joensuu et al. [2] randomly assigned 1,010 women with axillary node-positive or high-risk node-negative cancer to receive three cycles of docetaxel or vinorelbine, followed by three cycles of fluorouracil, epirubicin, and cyclophosphamide. The 232 women whose tumors had an amplified HER-2/ neu gene were assigned to receive or not to receive nine weekly trastuzumab infusions. Within the subgroup of patients with HER-2/neu-positive breast cancer, those who received trastuzumab had better 3-year recurrence-free survival than those who did not (hazard ratio [HR], 0.42; p = .01). Interestingly, the hazard ratio remained similar (0.41) when adjustment was made according to the type of chemotherapy given (trastuzumab combined with docetaxel or vinorelbine). Thus, even though, globally, recurrence-free survival at 3 years was better with docetaxel than with vinorelbine (HR, 0.58; p = .005), the concurrent administration of trastuzumab with one of these drugs was able to overcome this difference. Moreover, in the adjuvant setting, delayed administration of trastuzumab may be less effective than concurrent administration with paclitaxel [7]. Thus synergy for trastuzumab plus cytotoxic drug combinations is specific for HER-2-overexpressing tumor cells [3] and is not observed inHER-2-negative cells, which show different sensitivity to docetaxel or vinorelbine. References:
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