Bevacizumab (B) plus gemcitabine (G) in patient (pts) with advanced pancreatic cancer (PC): Updated results of a multi-center phase II trial
2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 14_suppl Linguagem: Inglês
10.1200/jco.2004.22.90140.4009
ISSN1527-7755
AutoresHedy L. Kindler, Gregory Friberg, Walter M. Stadler, D. A. Singh, Gershon Y. Locker, Sreenivasa Nattam, Mark Kozloff, Kristen Kasza, Everett E. Vokes,
Tópico(s)Colorectal Cancer Treatments and Studies
Resumo4009 Background: Vascular endothelial growth factor (VEGF) and its receptors are overexpressed in PC. In preclinical models, anti-VEGF antibodies suppress PC growth and potentiate the activity of gemcitabine. High VEGF expression correlates with advanced stage and decreased survival in PC pts. These data suggest that anti-VEGF therapy may have utility in PC. Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody to VEGF. Methods: We are conducting a phase II trial of BG in advanced PC pts at 8 centers. Eligible pts have no prior chemotherapy (except 5-FU as a radiosensitizer); PS 0–2; measurable disease; no tumor invasion of major vessels; no bleeding or thrombosis. G 1000 mg/m2 is given over 30 minutes days (D) 1, 8, 15 every 28 D. B 10 mg/kg is given D 1, 15 every 28D. CT scans are obtained every 2 cycles. Plasma VEGF levels are obtained pretreatment. 45 pts enrolled 11/01–12/03. Pt characteristics: male 47%; median age 61 (range 42–83); PS: 0/1/2: 62%/36%/2%; stage IV 100%; liver metastases 80%; prior radiation 18%. Results: 182 cycles of BG have been administered (median 3, range <1–11). 42 pts are currently evaluable for response in this ongoing trial (median follow-up 5.7 months). There are 9 confirmed partial responses (21% PR) lasting a median of 9.4 months. 19 pts (45%) had stable disease lasting a median of 5.4 months. Median time to progression is 5.8 months (95% CI: 4.8, 9.1). Median survival is 9.0 months (95% CI: 7.4, 12.4); 6-month survival is 74%. Grade ¾ toxicities (% pts): neutropenia 33%; leukopenia 30%; thrombocytopenia 7%; thrombosis 12%; bowel perforation 5%; hypertension, proteinuria, and headache 2% each. Grade 5 toxicities: 1 gastrointestinal bleed, 1 bowel perforation. Pretreatment plasma VEGF levels in 32 pts (range 0–586 pg/ml) showed no correlation with either response (Fisher's exact test p=1.00) or survival (Log rank test p=0.70). Conclusion: BG is active and well-tolerated in advanced PC. The median survival of 9.0 months and the 74% 6-month survival are encouraging. A randomized phase III trial of BG vs. G is in development in the Cancer and Leukemia Group B. Supported by NCI grant N01-CM-17102. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Lilly Oncology Genentech Lilly Oncology Lilly Oncology
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