Crane(ChemotherapyAdvisor) – In patients with locally advanced pancreatic cancer, radiotherapy with concurrent erlotinib, bevacizumab, and capecitabine is safe and tolerable, with “promising” overall survival rates and a high rate of resectability at higher dose levels, according to results of a Phase 1 study presented June 19 at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference, Lake Tahoe, NV.

Previously, adding bevacizumab to chemoradiotherapy for locally advanced pancreatic cancer has been shown to be safe. This study sought to determine safety, tolerability, and maximum tolerated dose (MTD) of erlotinib when added to this treatment regimen, noted Christopher H. Crane, MD, professor, of The University of Texas MD Anderson Cancer Center, Houston, TX.

The study enrolled 17 patients with CT-staged, biopsy-proven, nonmetastatic, unresectable locally advanced pancreatic cancer between March 2008 and October 2010; prior chemotherapy was permitted.

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All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab, and erlotinib. Two patients each were enrolled at dose levels 1-4 and 9 patients at dose level 5. Bevacizumab was escalated from 5mg/kg every 2 weeks (dose levels 1-4) to 10mg/kg (dose level 5); erlotinib from 100mg/day (dose levels 1-2) to 150mg/day (dose levels 3-5); and capecitabine from 400mg/m2 twice daily on days of radiation (dose level 1) to 600mg/m2 (dose levels 2-3) to 825mg/m2 (dose levels 4-5). At 6 to 8 weeks following treatment, patients were assessed for potential resection.

All adverse events reported were known radiation or chemotherapy effects. No grade 3 toxicities were observed in patients at dose levels 1-4 at a median follow-up of 10 months (range, 3-23 months); 3 patients (33%) at dose level 5 developed a grade 3 acute toxicity (2 diarrhea and 1 rash). No grade 4 or 5 toxicities were observed. Dose level 4 was selected as the MTD.

For all patients, median survival was 19.4 months and time to distant progression, 9.8 months; for those treated at dose levels 4 and 5, median survival was 24 months.

“Of 5 patients who underwent margin-negative resections, 4 had tumors that were originally deemed unresectable; 4 were treated at dose levels 4 or 5; 3 patients had excellent pathological responses at pancreatectomy and are alive at 13, 21, and 22 months, respectively, with no local or distant failures,” the investigators reported.

“This is the third single-arm study using erlotinib concurrently with radiotherapy that has resulted in encouraging median survival duration,” Dr. Crane said. “Both the promising survival and the high rate of resectability at the higher dose levels suggest that this strategy of dual inhibition of growth factor receptor pathways during chemoradiotherapy warrants continued evaluation,” he concluded.