11509 Background: The introduction of T for patients (pts) overexpressing HER-2 changed the natural history of BC. The adjunction of T to anthracyclines and taxanes for both LABC and MBC provided a significant incidence of unexpected cardiotoxicity. Given the low cardiac toxicity in our previous experience with weekly ET in unselected MBC pts, a feasibility phase II study aimed to cardiotoxicity was planned. Methods: Pts affected by untreated LABC/MBC overexpressing HER-2 by FISH/CISH amplification or 3-positive Dako- Test, underwent weekly T (4–2 mg/kg/week), day 1, and E (25 mg/m2/week) plus P (80 mg/m2/week), day 2, plus G-CSF support, for 16/24 consecutive weeks in absence of progression or toxicity, in LA/M pts, respectively. Pts with significant cardiac disease/L-FEV<50% were excluded. Primary endpoint was the rate of pts with L-FEV reduction >10% after 12 weeks. An optimal 2-stage Simon design was applied. With a power of 90% at a 5% significance level, assuming a toxicity rate of 30% as unacceptable, and less than 10% as acceptable, an initial group of 15 pts was required; with 11 pts with no toxicity, a second step with further 21 pts (total 36) was planned. Non-cardiac toxicity and activity were evaluated as secondary end-points. Results: From May 2004 to November 2006, 15 pts entered the study. Patient characteristics: median age=47 (range 37–69); LABC/MBC=4/11; positive hormonal receptor 8/7; menopausal pre/post=7/8; PS 0/1=14/1; number of met sites 1/2/3=7/6/2. Median baseline- and post-week-12-L-FEV was 69% (range 64–77) and 65% (range 61–76), respectively. With a median number of courses of 13 (range 8–24), 3 pts had a >10% L-FEV reduction (20%), with an overall median L-FEV reduction of 5.2%. No EKG alteration or specific symptoms were registered. With a 17-months median follow-up, 13 pts were evaluable for response. Eight response (61.5%, 95% CI 9- 87) were documented, with a median response duration of 9 months. No grade 3–4 toxicity were registered, with the exception of severe alopecia. Conclusions: The weekly administration of T plus E and P is extremely tolerable, also with regard to L-FEV reduction. The low L- FEV reduction rate allowed entering the second step of the study. No significant financial relationships to disclose.
Cardiac Toxicity of HER-2 Targeted Regimens
