Cetuximab toxicity

Cetuximab has modest activity in relapsed colorectal cancer as a single agent but is more effective with irinotecan and possibly oxaliplatin based regimens where a doubling of the response rate has been observed. There is some evidence that cetuximab may reverse irinotecan resistance. Toxic effects of cetuximab include hypersensitivity reactions, malaise, nausea, headache and an acneiform rash. 

Cetuximab Inhibition of EGFR sign ing apoptosis ADCC Loading dose of 400 mg/kg infusion followed by 250 mg/kg weekly Infusion-related toxicity skin rash in 75%... 

Cetuximab displays nonlinear pharmacokinetics. Following the recommended dose regimen, steady-state levels are achieved by the third weekly infusion. The mean t is 114 hours (range, 75—188 hours). Toxic side effects observed with cetuximab include infusion reactions. The incidence of rash is significantly greater than that observed with other monoclonal antibodies it may occur in 75% of patients, and may be severe in 16%. Interestingly, there is a correlation between development and intensity of rash and duration of benefit from cetuximab. 

Cetuximab EGFr Colorectal cancer Infusion reactions, skin rash, pulmonary toxicity... 

Tol J, Koopman M, Rodenburg CJ et al. (2008) A randomised phase 111 study on capecitabine, oxaliplatin and bevaci-zumab with or without cetuximab in first-line advanced colorectal cancer, the CA1R02 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol 19 734-738 Tournier C, Hess P, Yang DD et al. (2000) Requirement of JNK for stress-induced activation of the cytochrome c-medi-ated death pathway. Science 288 870-874... 

Like cetuximab, infliximab is a monse-hnman chimeric IgGlK mAb. With specificity for TNF, the antibody is used to treat autoimmune diseases snch as Crohn s disease and rheumatoid arthritis (Table 11.1) and there are a few reports of it indneing rapid recovery of lesions in several cases of toxic epidermal necrolysis (Sect. 3.63.1). A variety of reactions, both systemic and cutaneons, have been reported following administration of infliximab. These inclnde macnlopapular rashes, nrticaria, psoriasis, flare-np of atopic dermatitis. 

Cetuximab (Erbitux) EGER 2004 CV, pulmonary in monkeys J.BP, tHR, I RR rate, J, tidal volume ECG in monkey—no effect 9-month monkey Dermatologic toxicity and secondary infections Infusion reactions, cardiopulmonary arrest, pulmonary toxicity, dermatologic toxicity, hypomagnesemia... 

For panitumumab, a dedicated safety pharmacology study was conducted in monkeys (Vectibix Pharmacology Review US FDA 2006 Vectibix EPAR 2007). In this study, panitumumab produced no treatment-related effects on the cardiovascular, respiratory, and central nervous systems. In a 1-month toxicology smdy in monkeys, some cardiac toxicity was observed. However, this was subsequently shown to be due to electrolyte imbalance due to severe diarrhea (likely related to inhibition of EGF) and did not occur in subsequent studies in which supportive fluids were administered. In the 6-month repeated-dose toxicology study, the major toxicity was skin toxicity similar to that described for cetuximab. 

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