4098 Background: The combination of radiotherapy and chemotherapy is a mainstay for anal cancer. Improving local control could avoid mutilating salvage. We evaluate the role of an intensified strategy combining radio-chemotherapy with 5FU-cisplatinum and cetuximab for locally advanced anal cancer in the setting of a multicentric phase II trial.
METHODS
This study aimed to evaluate the response rate after radiotherapy and a concurrent 5FU-cisplatinum regimen combined to cetuximab. Patients (pts) with locally advanced anal cancer treated by radiotherapy combined to cisplatinum, 5FU and cetuximab. The primary end-point was local response rate 2 months after therapy. Secondary endpoints were progression-free survival, overall survival, colostomy-free survival and safety. A two-step design was used.
RESULTS
Between 03/09 and 05/10, 16 patients were included in 7 centers. All patients presented locally advanced tumors (5 extended to the vagina, 1 to the bladder). All were squamous cell carcinoma. Only 8 pts receive both the 6 cetuximab administrations and the two 5FU-cisplatinum cycles. Accrual was suspended after 10 pts after the occurrence of 10 serious adverse events (SAE) in 7 patients of which 6 SUSAR. The protocol was amended : decrease the 5FU and the cisplatinum dose, mandatory IMRT. After accrual of 6 additional pts, 6 SAE in 5 pts. Severe toxicities were: lymphopenia (8 pts), diarrhea (6 pts), fatigue (6 pts), neutropenia (5 pts), acneiform rash (4 pts), thrombopenia (4 pts), hypoNa or K (4 pts); radioepithelitis 3 pts. 3 pts had severe toxicity between 3-6 months follow-up: radio-necrosis pelviperineal (1 pts); mucitis and acneiform rash (1 pts); febrile syndrome (1 pts). After exclusion of the 3 pts with early withdrawal and with a 14 months median follow-up, median PFS is 9 months and one-year survival rate 91%. (local failure (4 pts), metastasis (1 pts). 4 patients had colostomy (2 for local relapse, 2 for fistulisation).
CONCLUSIONS
The IDMC decided to stop the trial after the first 16 patients for a high rate of toxicity and an insufficient efficacy. This regimen is not recommended combined with RT even in case of locally advanced disease.