Otilia Leon1, Marianne G Guren2, Calin Radu3, Adalsteinn Gunnlaugsson4, Anders Johnsson4. 1. Department of Oncology, Skåne University Hospital, Lund, Sweden. Electronic address: otilia.leon@skane.se. 2. Department of Oncology, Oslo University Hospital, Oslo, Norway; K.G.Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway. 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 4. Department of Oncology, Skåne University Hospital, Lund, Sweden.
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.
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.
Authors: Madhur K Garg; Fengmin Zhao; Joseph A Sparano; Joel Palefsky; Richard Whittington; Edith P Mitchell; Mary F Mulcahy; Karin I Armstrong; Nassim H Nabbout; Shalom Kalnicki; Bassel F El-Rayes; Adedayo A Onitilo; Daniel J Moriarty; Thomas J Fitzgerald; Al B Benson Journal: J Clin Oncol Date: 2017-01-09 Impact factor: 44.544
Authors: Corinne M Doll; Jennifer Moughan; Alexander Klimowicz; Clement K Ho; Elizabeth N Kornaga; Susan P Lees-Miller; Jaffer A Ajani; Christopher H Crane; Lisa A Kachnic; Gordon S Okawara; Lawrence B Berk; Kevin S Roof; Mark J Becker; David L Grisell; Robert J Ellis; Paul W Sperduto; Gerald W Marsa; Chandan Guha; Anthony M Magliocco Journal: Int J Radiat Oncol Biol Phys Date: 2016-11-23 Impact factor: 7.038