Non-targeted Drugs for Cancer Therapy

Abstract

In a 2017 analysis, 61 of 150 anticancer drugs approved by the FDA were classified as cytotoxic and 89 as targeted drugs. For many years, cytotoxic compounds have been the front line of cancer chemotherapy, but their action of destroying rapidly dividing cancer and healthy cells in the gut, bone marrow, and hair follicles causes undesirable side effects like mucositis, stomatitis, myelosuppression, and alopecia. Hypersensitivities commonly occur. Drugs with high potential to provoke hypersensitivity are platinum compounds, taxanes, epipodophyllotoxins, L-asparaginase, and procarbazine. Those with low potential include the anthracyclines. Drugs only occasionally implicated include cyclophosphamide and methotrexate. Immediate type I allergic reactions are few with L-asparaginase, the platinum salts, and methotrexate most often implicated. Type II hypersensitivities are thrombocytopenia, drug-induced neutropenia, and drug-induced anemia. Small-vessel vasculitis is the most frequently seen form of a type III reaction. Hypersensitivity pneumonitis is a combined type III and type IV hypersensitivity. Drug-induced liver injury may occur, and drug-induced lung disease may be due to drug-specific antibodies or drug-specific T cells. Drug-induced cutaneous reactions include maculopapular exanthemas, allergic contact dermatitis, psoriasis, AGEP, DRESS, fixed drug eruptions, erythema multiforme, SJS, and TEN. A variety of other cutaneous and mucocutaneous reactions associated with chemotherapy include stomatitis and mucositis, acral erythema, neutrophilic eccrine hidradenitis, eccrine squamous syringometaplasia, extravasation reactions, and radiation-associated reactions. For the prevention of allergic reactions, three strategies are generally employed: premedication, skin testing, and desensitization. Up to 30% of patients have been found to develop acute infusion reactions to the taxanes; rapid desensitization protocols have been developed for both drugs. Three platinum drugs, cisplatin, carboplatin, and oxaliplatin are often used in chemotherapy. Reactions to platinum agents are mainly type I or type IV hypersensitivities; IgE antibodies reactive with carboplatin and oxaliplatin have been detected. Skin testing with the three platinum drugs is now finding widespread acceptance and application as a routine diagnostic procedure. A number of different desensitization protocols for the platinum drugs are currently employed.