RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance, and enhance clinical benefit. Further development of cetuximab, pemetrexed, and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified.

The addition of pemetrexed 500 mg/m(2) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients.

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6051 Background: E is a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor that may enhance the efficacy of RT and chemotherapy. Our goal was to incorporate E in the induction and subsequent chemoradiotherapy of HNSCC. We report our preliminary results with TPE induction. Methods: Patients (pts) had pathologically documented HNSCC stage III/IV or selected stage II (base of tongue, hypopharynx, or nasopharynx), no prior therapy, ECOG PS 0–1, and adequate hematologic, kidney and liver laboratory parameters. Induction consisted of T 75 mg/m2 day 1, P 75 mg/m2 day 1, and E 250 mg/m2 days 1,8, and 15 (after an initial dose of 400 mg/m2 on cycle 1, day 1), repeated every 21 days × 3 cycles. Subsequently, pts received RT 70 Gy (2 Gy/day) with concurrent P 30 mg/m2 and E 250 mg/m2 weekly, followed by maintenance E for 6 months. Prophylactic antibiotics were given on days 5–14 of each TPE cycle. Tumor assessment was performed after induction (primary endpoint) and 8 weeks after RT. Sample size was 39; one-stage design; target overall response rate (ORR): 80%. Results: 21 pts have been enrolled to date: median age 55 (39–74); Male/Female: 18/3; primary site: oropharynx (n=13), larynx (n=5), and other (n=3); stage III/IV: 4/17. In 16 evaluable pts, ORR to TPE was 15/16 (94%), CR: 2, PR 13, SD 1. For the primary site (12 evaluable): CR 6, PR 5, SD 1; for the lymph nodes (14 evaluable): CR 1, PR: 12, SD 1. The pt with SD discontinued E in the first cycle due to recurring infusion reaction. Another patient had a grade (G) 3 infusion reaction on the first E administration and was removed from study. Other serious toxicities during TPE (n=20): grade (G) 3/4 neutropenia (n=4/n=7) without incidence of neutropenic fever, G 3 anemia (n=1), G 3 thrombocytopenia (n=1), G 3/4 hypomagnesemia (n=2/n=1), G 3 rash (n=1), G 3 fatigue (n=4), and G 3 diarrhea (n=1). 1 pt had sudden death due to myocardial infarction (autopsy) after the third cycle of TPE. Subsequent RT plus P and E was feasible. 10 pts completed RT and all remain progression-free. Conclusions: Preliminary results suggest that TPE has predictable and manageable toxicities and high activity in HNSCC. Accrual is ongoing and updated data will be available. No significant financial relationships to disclose.