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Anthracycline and Trastuzumab in Breast Cancer Treatment

This study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastaticbreast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) incomparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those withmetastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapyfor metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, openlabel,phase II study in Germany. A control group of 23 patients received EC 90/600 mg/m2 3-weekly for sixcycles (EC90 alone). A total of 26 HER2-positive patients were treated with trastuzumab, or H (2 mg/kg weeklyafter an initial loading dose of 4 mg/kg), and EC 60/600 mg/m2 3-weekly for six cycles (EC60+H); another 25HER2-positive patients received H and EC 90/600 mg/m2 3-weekly for six cycles. Asymptomatic reductions inleft ventricular ejection fraction (LVEF) of more than 10% points were detected in 12 patients (48%) treatedwith EC60 + H and in 14 patients (56%) treated with EC90 + H vs 6 patients (26%) in the EC90 alone cohort.LVEF decreases to < 50% occurred in one patient in the EC60+H cohort and in two patients in the EC90+Hcohort during the H monotherapy. No cardiac event occurred in the cohort with EC90 alone. The overallresponse rates for EC60+H and EC90+H were >60%, vs 26% for EC90 alone. The interim results of this studysuggest the cardiac safety of the combination of H with EC may be greater than that of H with AC (doxorubicin[Adriamycin]/cyclophosphamide); however, studies in larger numbers of patients are warranted. The combinationregimen revealed promising efficacy.

Latest Article

Irinotecan/Cisplatin Followed by 5-FU/ Paclitaxel/Radiotherapy and Surgery in Esophageal Cancer

Local-regional carcinoma of the esophagus is often diagnosed inadvanced stages because the diagnosis is established when symptomsare severe. The prognosis of patients with local-regional carcinoma ofthe esophagus continues to be grim. While preoperative chemoradiotherapyincreases the fraction of patients who achieve pathologiccomplete response, that percentage is approximately 25%. In an attemptto increase the number of patients with either no cancer in the surgicalspecimen or only microscopic cancer, we adopted a three-step strategy.The current study utilized up to two 6-week cycles of induction chemotherapywith irinotecan (CPT-11, Camptosar) and cisplatin as step 1.This was followed by concurrent radiotherapy and chemotherapy withcontinuous infusion fluorouracil (5-FU) and paclitaxel as step 2. Oncethe patients recovered from chemoradiotherapy, a preoperative evaluationwas performed and surgery was attempted. All patients signed aninformed consent prior to their participation on the study. A total of 43patients were enrolled. The baseline endoscopic ultrasonography revealedthat 36 patients had a T3 tumor, five patients had a T2 tumor, andtwo had a T1 tumor. Twenty-seven patients had node-positive cancer(N1). Thirty-nine (91%) of the 43 patients underwent surgery; all hadan R0 (curative) resection. A pathologic complete response was noted in12 of the 39 patients. In addition, 17 patients had only microscopic(< 10%) viable cancer in the specimen. Therefore, a significant pathologicresponse was seen in 29 (74%) of 39 taken to surgery or 29 (67%)of all 43 patients enrolled on the study. With a median follow up beyond25 months, 20 patients remain alive and 12 patients remain free ofcancer. Our preliminary data suggest that the proportion of patientswith significant pathologic response can be increased by using thethree-step strategy.