Cetuximab: in the treatment of metastatic colorectal cancer.
Cetuximab is a chimeric monoclonal antibody highly selective for the epidermal growth factor receptor (EGFR), which is over-expressed by 25-80% of colorectal cancer tumours and associated with advanced disease. Cetuximab induces a broad range of cellular responses in tumours expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. In a large, randomised, open-label, multicentre study in adult patients with irinotecan-refractory, metastatic colorectal cancer expressing EGFR, cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly plus irinotecan (various doses) produced a greater rate of partial response and disease control (partial response plus stable disease), and increased time to disease progression, compared with cetuximab monotherapy; survival was similar in both groups. The same dosage of cetuximab combined with irinotecan, fluorouracil and folinic acid (various regimens) produced partial responses in 43-58% of patients, a complete response in 5% of patients (one study only) and stable disease in 32-52% of patients with treatment-naive metastatic colorectal cancer expressing EGFR in three small, open-label trials. The most common grade 3/4 adverse events associated with cetuximab monotherapy were acne-like rash, asthenia, abdominal pain and nausea/vomiting. In patients receiving cetuximab plus irinotecan, these were diarrhoea, asthenia, leucopenia and neutropenia.
Reynolds
Neil A
NA
Adis International Limited, Mairangi Bay, Auckland 1311, New Zealand. demail@adis.co.nz
Wagstaff
Antona J
AJ
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab