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Camden, NJ, United States

Esteva F.J.,University of Houston | Franco S.X.,Memorial Cancer Institute | Hagan M.K.,Virginia Cancer Institute | Brewster A.M.,University of Houston | And 6 more authors.
Oncologist | Year: 2013

Background. Recent data support the hypothesis that combining lapatinib and trastuzumab with taxane chemotherapy may offer added clinical benefit to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study examined the safety of the triplet combination in first-line HER2-positive MBC. Patients and Methods. Patients were enrolled into three sequential cohorts; the last two cohorts were added by protocol amendmentfollowing review of safety data from cohort 1. Patients in cohort 1 received lapatinib (1000 mg/day) plus paclitaxel (80 mg/m2 per week, 3 of every 4 weeks); cohort 2 received lapatinib (1000 mg/day) plus paclitaxel (70 mg/m2 per week, 3 of every 4 weeks); and cohort 3 received lapatinib (750 mg/day) plus paclitaxel (80mg/m2 per week, 3 of every 4 weeks). All received standard trastuzumab dosing. The primary objective was assessment of dose-limiting toxicities, safety, and tolerability of this combination. Results. The most frequent adverse events (AEs) for all cohorts were diarrhea (89%), rash (79%), fatigue (73%), alopecia (63%), nausea (63%), and vomiting (40%). In cohorts 1 and 2, the incidence of grade 3 diarrhea was 62% and 50%, respectively; in cohort 3, the incidence was 25% (with prophylactic loperamide). Dehydration was the most frequent serious AE (10%). Across cohorts, overall response rate was 75%. Conclusions. The dose-limiting toxicity of paclitaxel, trastuzumab, and lapatinib in first-line HER2-positiveMBCwas diarrhea. Of the triplet combinations tested, the cohort receiving 750 mg/day dose of lapatinib had the lowest incidence of diarrhea; therefore, this dose should be used in further studies on the treatment of MBC. © AlphaMed Press 2013. Source

Stevenson J.P.,University of Pennsylvania | Langer C.J.,University of Pennsylvania | Somer R.A.,Cooper Cancer Institute | Evans T.L.,University of Pennsylvania | And 9 more authors.
Cancer | Year: 2012

Background: The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer. Methods: Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m2 and carboplatin at an area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression. Results: In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment-related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow-up of 15.8 months, the median progression-free survival was 7.1 months (95% confidence interval, 5.9-8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8-25.5 months). Conclusions: Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer. © 2012 American Cancer Society. Source

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