Cetuximab Plus Cisplatin, Irinotecan, and Thoracic Radiotherapy as Definitive Treatment for Locally Advanced, Unresectable Esophageal Cancer: A Phase-II Study of The SWOG (S0414)

• DOI: 10.1097/jto.0b013e31824c7bed
• Publication Date: 2012-04-05T09:52:14Z
• Authors: Michael B. Tomblyn; Bryan H. Goldman; Charles R. Thomas; Jacqueline K. Ben...; Heinz-Josef Lenz; Vivek Mehta; Thaddeus Beeker; Philip J. Gold; James L. Abbruzzese; Charles D. Blanke
• Keywords: Pulmonary and Respiratory Medicine; Adult; Male; 0301 basic medicine; Esophageal Neoplasms; Cetuximab; Adenocarcinoma; Antibodies, Monoclonal, Humanized; Irinotecan; 03 medical and health sciences; Antineoplastic Combined Chemotherapy Protocols; Humans; Esophageal; Aged; Neoplasm Staging; Aged, 80 and over; Radiotherapy; Antibodies, Monoclonal; Chemoradiotherapy; Middle Aged; Prognosis; 3. Good health; Oncology; Carcinoma, Squamous Cell; Camptothecin; Female; Cisplatin

Introduction:The specific aims of the study were to evaluate 2-year overall survival (OS) and progression-free (PFS), toxicity profile, best objective response rate in patients with locally advanced, clinically unresectable esophageal cancer receiving cetuximab, cisplatin, irinotecan, thoracic radiotherapy (TRT) within a multi-institutional cooperative-group setting.Methods:Eligible (cT4 M0 or medically unresectable, biopsy proven, noncervical cancer) receive four 21-day cycles cetuximab 400 mg/m2 (day 1, cycle 1), 250 8, 15, 1; then days 15 for subsequent cycles), cisplatin 30 (days 1 all irinotecan 65 cycles). TRT was administered at 1.8 Gy 28 daily fractions total dose 50.4 Gy, begin on day 3. The primary endpoint OS, an accrual goal 75 adenocarcinoma.Results:The closed because slow accrual, 21 eligible (11 squamous, 10 adenocarcinoma) enrolled from May 2005 September 2007. Two-year OS PFS (95% confidence interval [CI]) 33.3% (14.6–57.0%) 23.8% (8.2–47.2%), respectively. Kaplan–Meier estimates median CI) 11.2 (6.4–43.6) 6.4 (3.7–12.0) months, among 17 evaluable 17.6% (3.8–43.4%), including 6% confirmed complete responders 12% unconfirmed partial responders. Two deaths resulted protocol treatment (sudden death gastrointestinal necrosis). Ten (47.6%) 6 (28.6%) had grade-3 -4 toxicity, respectively: 52.4% hematologic, fatigue, 19.0% nausea, dehydration, anorexia.Conclusions:Concomitant poorly tolerated first North American cooperative group trial testing this regimen advanced as treatment-related mortality approached 10%. Single-institution phase-II cetuximab-based combined modality trials have yielded encouraging results preliminary analyses. SWOG GI Committee endorses enrollment open clinical clarify therapeutic ratio approaches cancer.