Preliminary toxicity results of a phase II trial of adjuvant docetaxel/cyclophosphamide plus trastuzumab in HER2+ early stage breast cancer patients

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 2_Supplement; p. 2111
• Main Authors: Jones, SE, Collea, RP, Oratz, R, Paul, D, Sedlacek, SM, Holmes, FA, Portillo, RM, Crockett, MW, Asmar, L, O'Shaughnessy, JA, Robert, NJ
• Format: Journal Article
• Language: English
• Published: 15-01-2009
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-2111

Abstract #2111
Background: Docetaxel/cyclophosphamide (TC) has demonstrated superior activity to doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of patients (pts) with early breast cancer and is devoid of known cardiac toxicity (Jones et al, SABCS 2007, abstract 12). Although the addition of trastuzumab (H) to anthracycline-based adjuvant regimens has proven effective, it has also been associated with increased cardiac toxicity. Therefore, a short course of the nonanthracycline TC regimen coupled with H appeared to be a logical combination for women with lower risk HER2+ breast cancer. We report safety and tolerability of the TC+H regimen.
 Patients and Methods: 256 of a planned 260 patients (pts) were registered to the study and stratified by positive or negative nodes. On Day 1 of each 21-day cycle for a total of 4 cycles, pts received (in order): (T) 75 mg/m2 IV, followed by (C) 600 mg/m2 IV. Weekly (H) was also given at 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (Days 1, 8, 15) thereafter throughout chemotherapy. After completion of chemotherapy, H was administered at a dose of 6 mg/kg IV every 3 weeks to complete 12 months of therapy with H. Pts must have had LVEF >50% at the time of registration and had regular cardiac evaluation throughout the study (MUGA or ECHO).
 Results: To date, 231 pts were treated and comprise the safety population; this first report focused on toxicity occurring during the first 4 months of co-administration of chemotherapy and H. The median age was 55 years; 84% of pts were ECOG 0; 61% were ER+. Selected treatment-related toxicities in ≥3% of pts are listed in Table 1. Of the 231 pts, 10 pts came off treatment due to adverse events: hypersensitivity (3), gastrointestinal (2), hematologic (2), pulmonary (1), skin (1), and cardiac (1). To date, only 1 patient has had a significant drop in LVEF to 40%, and was taken off treatment.
 
 Conclusion: 4 cycles of TC combined with H is a well-tolerated adjuvant treatment with an acceptable toxicity profile for lower risk patients with HER2+ breast cancer.
 This research was supported, in part, by a research grant from sanofi-aventis, Bridgewater, NJ.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2111.