Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer
Mené sur 11 patients atteints d'un cancer de l'anus de stade localement avancé (âge médian : 65 ans ; 2 hommes et 9 femmes), cet essai de phase I évalue la dose maximale tolérée du 5 fluorouracile et de la mytomicine C dans le cadre d'une chimioradiothérapie en combinaison avec le cétuximab
Background : 5-fluorouracil (5FU) and mitomycin C (MMC)-based chemoradiotherapy (CRT) is standard treatment for anal squamous cell carcinoma. In this phase I study cetuximab was added and the primary aim was to determine the maximum tolerated dose (MTD) of 5FU and MMC in this combination. Methods and materials : Patients with locally advanced anal cancer, T2 (≥4 cm)–4N0–3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule. Results : Thirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46–70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3–4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%. Conclusion : The MTDs were determined as 5FU 800 mg/m2 on RT days 1–4 and 29–32 and MMC 8 mg/m2 on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.