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

AbstractBACKGROUND:
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.
AuthorsOtilia Leon, Marianne G Guren, Calin Radu, Adalsteinn Gunnlaugsson, Anders Johnsson
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 51 Issue 18 Pg. 2740-6 (Dec 2015) ISSN: 1879-0852 [Electronic] England
PMID26597443 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Mitomycin
  • Cetuximab
  • Fluorouracil
Topics
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Anus Neoplasms (pathology, therapy)
  • Carcinoma, Squamous Cell (secondary, therapy)
  • Cetuximab (adverse effects, therapeutic use)
  • Chemoradiotherapy (adverse effects)
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Fluorouracil (adverse effects, therapeutic use)
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms (secondary)
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Mitomycin (adverse effects, therapeutic use)
  • Neoplasm Staging
  • Norway
  • Prospective Studies
  • Radiotherapy, Intensity-Modulated (adverse effects)
  • Remission Induction
  • Sweden
  • Time Factors
  • Treatment Outcome

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