A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC).
281 Background: Localized PC is commonly managed with chemoradiotherapy, with or without surgical resection. The optimal combination of agents and doses is the subject of continued investigation. This phase I study examines the combination of two targeted radiosensitizing agents in combination with radiation therapy. METHODS: Eligible patients had resectable, borderline resectable or locally advanced adenocarcinoma. Patients received RT (1.8 Gy qd to 50.4 Gy) concurrent with bevacizumab and erlotinib. Dose-level 1 was bevacizumab 10 mg/kg weeks 1, 3 and 5 and erlotinib 100 mg daily, RT days only. Drug doses were escalated depending on encountered toxicity. The primary endpoint was determination of the maximally tolerated dose of this combination. Secondary endpoints included toxicity and activity assessment. RESULTS: Nine patients were enrolled in the phase I study. Maximal EUS/CT stage was T2N0 (n=1), T3N0 (n=1), T3N1 (n=2) or T4N0 (n=5). Of 3 patients in dose-level 1, two had radiographic stable disease (SD) and one partial response (PR). One pt underwent exploratory laparotomy and found to be unresectable, experiencing prolonged postoperative incisional healing. Three patients were then enrolled at dose-level 2 (bevacizumab 10 mg/kg, erlotinib 125 mg). Two had SD and one progressive disease (PD). One pt underwent exploratory laparotomy, aborted due to previously undetected hepatic metastases. Three patients were then enrolled at dose-level 3 (bevacizumab 10 mg/kg, erlotinib 150 mg). One pt had SD and two PR. One pt underwent distal pancreatectomy, experiencing postoperative pancreatic leak and abscess formation. All patients with elevated CA 19-9 at baseline had a decrease, with amedian decrease of 69% (R:13-93%). Dose-limiting toxicity (DLT) was not encountered at any dose-level. Primary non-dose limiting toxicities in all cohorts included NCI CTCAE v3.0 grade 1-2 nausea/vomiting, rash, diarrhea, fatigue, and anorexia. CONCLUSIONS: Concurrent chemoradiotherapy utilizing erlotinib and bevacizumab is reasonably well-tolerated. The recommended phase II dose is bevacizumab 10 mg/kg weeks 1, 3, and 5 and erlotinib 150 mg RT days only. Phase II accrual is underway. [Table: see text].
Czito, BG; Willett, C; Kennedy-Newton, P; Tyler, DS; Hurwitz, H; Uronis, HE
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