Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer. Issue 18 (December 2015)

• Record Type: Journal Article
• Authors: Leon, Otilia; Guren, Marianne G.; Radu, Calin; Gunnlaugsson, Adalsteinn; Johnsson, Anders
• Is Part Of: European journal of cancer. Volume 51:Issue 18(2015:Dec.)
• Page Start: 2740
• Page End: 2746
• Publication Date: 2015-12
• Subjects: Anal cancer -- 5-Fluorouracil -- Mitomycin C -- Cetuximab -- Phase I -- Radiotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.08.029
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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/m 2 on RT days 1–4 and 29–32 and MMC 8 mg/m 2 on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer. Highlights: Cetuximab was added to chemoradiotherapy in anal cancer in a phase I study. Dose-limiting toxicities were diarrhoea and myelotoxicity. Maximum tolerated doses of 5-fluorouracil and mitomycin C were determined.