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Purpose: HER-2 gene amplification in breast cancer patients on chemotherapy and endocrine therapy resistance and disease recurrence and risk of death will increase, targeted therapy targeting HER-2 positive HER-2 overexpressing breast cancer treatment hot spots. Lapatinib is a novel dual tyrosine kinase inhibitor (Tyrosine Kinase Inhibitor, TKI), role of HER-1 and HER-2 two targets at the same time, this paper investigates Lapatinib (GW572016) in combination with paclitaxel versus paclitaxel plus placebo phase compared the efficacy and safety of treatment of HER-2 overexpressing metastatic breast cancer, and paclitaxel treatment failure application Lapatinib efficacy and safety. Methods: This study prospective analysis from February 2006 to September 2008 into the group of international, multi-center EGF104535 trial of 32 patients with clinical data, evaluate Lapatinib (combined group) in combination with paclitaxel versus paclitaxel plus placebo (control group) compared the efficacy and safety of treatment of HER-2 overexpressing metastatic breast cancer patients, patients from the First Affiliated Hospital of Dalian Medical University, the Second Affiliated Hospital of Dalian Medical University and the Cancer Prevention Research Institute of Shandong Province, which is a joint group of 15 cases , 17 cases of the control group. Two groups of patients were randomized, double-blind receive paclitaxel 80mg/m2 intravenous infusion once a week, once every three weeks, one week rest, application of up to six cycles, combined with Lapatinib 1500mg, once a day;, or in combination with placebo daily once. Disease progression unblinded, control group, I Lapatinib 1500mg, once a day for eight weeks for a course of treatment. Solid Tumors Response Evaluation Criteria (Response Evaluation Criteria In Solid Tumour, RECIST) every 8 weeks for efficacy evaluation of anti-cancer drugs by the U.S. National Cancer Institute (NCI) acute and subacute toxicity performance and grading standards CTCAE3.0 version ( Common Terminology Criteria Of Adverse Events v3.0, NCI-CTCAEv3.0) security assessment. Results: 1 efficacy analysis was by intention (Intension-To-Treat, ITT) analysis, the combined group of 15 cases: complete remission (Complete response, CR) 2 patients, partial remission (PartialResponse, PR) 7 cases of stable disease (Stable Disease, SD ≥ 24 weeks) one cases of disease progression (Progressive Disease, PD) 5 the efficiency (Response rate, RR) 60%, disease control rate (Disease Control Rate, DCR) 66.6%; 17 cases of the control group: CR 0, PR, SD, PD 12 cases, RR 23.5%, DCR 29.4%. Statistical analysis showed that the combination group RR and DCR higher than that of the control group, there are significant differences. 2, the median time to disease progression (Time To Progression, TTP), the combined group was 37.4 weeks, the control group at 24 weeks (P = 0.021), a significant difference. 3, the most common adverse reactions in the two groups of neutrophils decreased (73% vs82%), alopecia (46% vs47%), rash (46% vs23%, P = 0.04), diarrhea (53% vs11%, P = 0.015), rash and diarrhea, the incidence of the combination group was significantly higher than that of the control group, and well tolerated. 4,17 cases of paclitaxel in the treatment of patients who failed to Lapatinib treatment, 1 CR, PR, SD 2, PD 12 cases, RR 17.6%, 29.4% DCR, median TTP was 21.8 weeks. Lapatinib single-agent treatment of common adverse reactions are rash (41%), diarrhea (35%), and well tolerated. Conclusion: Lapatinib was combined with paclitaxel in the treatment of HER-2 positive metastatic breast cancer more effective than paclitaxel single-agent RR 60%, 66.6% DCR, median TTP 37.4 weeks, were significantly higher than the control group. 2, a joint group of common adverse reactions were neutropenia (73%), alopecia (46%), rash (46%), diarrhea (53%), security, similar to the control group. 3, paclitaxel treatment failure to Lapatinib is still valid, RR 17.6% 29.4%, the DCR a median of TTP21.8 weeks. 4, Lapatinib single drug adverse reactions were rash (41%), diarrhea (35%), multi-Ⅰ / Ⅱ level.
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