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Eur J Cancer. 2015 Dec;51(18):2740-6. doi: 10.1016/j.ejca.2015.08.029. Epub 2015 Nov 18.

Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer.

Author information

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01621217.

KEYWORDS:

5-Fluorouracil; Anal cancer; Cetuximab; Mitomycin C; Phase I; Radiotherapy

PMID:
26597443
DOI:
10.1016/j.ejca.2015.08.029
[Indexed for MEDLINE]

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