A phase II study to determine the ability of gefitinib to reverse fluoropyrimidine resistance in metastatic colorectal cancer (the INFORM study)

• Published in: British journal of cancer Vol. 98; no. 4; pp. 716 - 719
• Main Authors: Stebbing, J, Harrison, M, Glynne-Jones, R, Bridgewater, J, Propper, D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.02.2008; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemotherapy, Adjuvant; Clinical Study; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Drug Resistance; Drug Resistance, Neoplasm; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; Molecular Medicine; Oncology; Pyrimidines - pharmacology; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; 5-fluorouracil; refractory; phase II; gefitinib; colorectal cancer; Antineoplastic agent; Rectal disease; Quinazoline derivatives; Colorectal cancer; Metastasis; Cancerology; Phase II trial; Intestinal disease; Advanced stage; Gefitinib; Protein-tyrosine kinase; Fluorouracil; Treatment resistance; Enzyme; Tyrosine kinase inhibitor; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Malignant tumor; Thymidylate synthase; Colonic disease; Treatment; Antimetabolic; Methyltransferases; Pyrimidine derivatives; Digestive diseases; Reversibility; colorectal cancer gefitinib; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604232

There are data suggesting that inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase signalling may reverse resistance to fluoropyrimidine treatment. To investigate this further, the INFORM study was an open-label, non-comparative phase II study of gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE, USA) 250 mg daily in combination with 5-fluorouracil (5-FU administered as an intravenous 400 mg m −2 bolus injection followed by 2800 mg m −2 infusion over 46 h and folinic acid administered as a 350 mg infusion over 2 h) every 2 weeks for up to 12 cycles in 24 patients with metastatic colorectal cancer refractory to previous fluoropyrimidine treatment. There were no objective responses. The stable disease rate was 37.5% (95% CI: 18.80, 59.41), median progression-free survival measured 116 days and overall survival was 226 days. Quality of life was unchanged compared to baseline values, and the commonest toxicities were diarrhoea, rash and fatigue with 7 out of 24 (29%) patients having a grade 3 or 4 toxicity. Gefitinib does not sensitise patients with fluoropyrimidine refractory metastatic colorectal cancer to 5-FU chemotherapy.