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Table 2. Recovery of Patients Reporting Symptoms of Possible CHF.


AC→PTX AC→PTX + H


Confirmed CHF (n) Followed ≥ 6 mos. From Dx of CHF Symptoms during past 6 mos. On meds during past 6 mos.


Not confirmed with CHF (n) Followed ≥ 6 mos. from symptoms Symptoms during past 6 mos. On meds during past 6 mos.


6 4


2/4 2/4


14 9


0/9 1/9


35 33


5/33 20/33


49 48


0/48 10/48


By individual risk factor, the incidence of heart failure was 5.4% for patients >65 compared with 2.3% for those 65 (Table 3), Dr. Rastogi reported.


Table 3. Risk Factors for Cardiac Toxicity. Risk Factors


No. of


Hypertensive medications


Diabetes medications


Lipid medications


Baseline LVEF


No Yes


No Yes No Yes





patients 732 192


897 37


857 68


70 452 425


111 468


351


No. with CHF (%) 22 (3.0%) 13 (6.8%)


35 (3.9) 0 (0.0%) 34 (4.0%) 1 (1.5%)


9 (12.9%) 17 (3.8%)


9 (2.1%)


14 (12.6%) 17 (3.6%)


4 (1.1%)


Relative Risk


(95% CI) 2.3 (1.2 – 4.6) ---- 0.4


(0.1 – 2.7) Ref. group 0.3


(0.1 – 0.6) 0.2


(0.1 - 0.4) Ref. group 0.3


(0.1 – 0.6) 0.1


(0.03 – 0.3)


A prediction model incorporating these risk factors was able to show, for example, that cardiac risk was only 1.3% for a 48-year-old female with a baseline ejection fraction of 69% who was not on antihypertensive medication, but rose to 15% in a 57-year-old patient with an ejection fraction of 54% who was on a blood pressure-lowering agent.


Dr. Rastogi advised clinicians to consider individual risk for cardiac events when deciding whether to administer trastuzumab.


Taxanes Comparable in Adjuvant Regimen


In adjuvant regimens for early breast cancer, the choice of taxane—docetaxel or paclitaxel—may be unimportant in terms of disease-free survival, according to the final results from the phase 3 Intergroup Trial E1199, reported by Joseph Sparano, MD, Albert Einstein College of Medicine, New York.


Evidence has suggested that docetaxel is more effective than paclitaxel, and paclitaxel is more effective when given weekly versus every 3 weeks in metastatic breast cancer. This study evaluated these agents and schedules in the adjuvant setting.


E1199 randomized 4590 patients with node-positive or high-risk node-negative breast cancer to doxorubin 60 mg/m2


plus cyclophosphamide 600 mg/m2 (AC) every


3 weeks for 4 cycles, followed by either (1) paclitaxel 175 mg/m2 80 mg/m2


every 3 weeks for 4 cycles, (2) paclitaxel weekly for 12 cycles, (3) docetaxel 100 mg/m2


every 3 weeks for 4 cycles, or (4) docetaxel 35 mg/m2 weekly for 12 cycles. The primary comparisons included taxane (docetaxel vs paclitaxel) and schedule (weekly vs every 3 weeks).


At a median follow-up time of 64 months, no differences in disease-free survival (DFS) were shown. There was, however, a 5% absolute improvement in DFS with paclitaxel given weekly and with docetaxel given every 3 weeks, and a 3% absolute improvement in overall survival with paclitaxel given weekly, Dr. Sparano reported.


“Compared with paclitaxel, docetaxel did not improve disease-free survival. And compared with a regimen given every 3 weeks, weekly treatment did not improve disease- free survival,” he said, referring to the primary endpoints (Table 1).


Table 1. Outcomes by Taxane and Regimen. Regimen


Disease-Free Survival


Paclitaxel q 3 weeks Paclitaxel weekly


Docetaxel q 3 weeks Docetaxel weekly


76.9% 81.5% 81.2% 77.6%


Overall Survival


86.5% 89.7% 87.3% 86.2%


With weekly paclitaxel and q-3-week docetaxel, the risk of disease progression was reduced by 25%. Similar trends observed in hormone receptor-negative and hormone receptor-positive patients. Weekly paclitaxel


Highlights from the American Society of Clinical Oncology Annual Meeting 2007


15


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