Cytotoxic agents toxicity

Clinically, GM-CSF or G-CSF have been used to accelerate recovery after chemotherapy and total body or extended field irradiation, situations that cause neutropenia and decreased platelets, and possibly lead to fatal septic infection or diffuse hemorrhage, respectively. G-CSF and GM-CSF reproducibly decrease the period of granulocytopenia, the number of infectious episodes, and the length of hospitalization in such patients (152), although it is not clear that dose escalation of the cytotoxic agent and increased cure rate can be rehably achieved. One aspect of the effects of G-CSF and GM-CSF is that these agents can activate mature cells to function more efficiently. This may, however, also lead to the production of cytokines, such as TNF- a, that have some toxic side effects. In general, both cytokines are reasonably well tolerated. The side effect profile of G-CSF is more favorable than that of GM-CSF. Medullary bone pain is the only common toxicity. 

In addition to antineoplastic, cytotoxic agents, there are cancer therapeutic or preventative drugs that are intended to be given on a chronic basis. This includes chemopreventatives, hormonal agents, immunomodulators, and so on. The toxicity assessment studies on these will more closely resemble those of more traditional pharmaceutical agents. Chronic toxicity, carcinogenicity, and Ml developmental toxicity (ICH A-B, C-D, E-F) assessments will be required. For a more complete review, the reader is referred to DeGeorge et al. (1998). 

Methotrexate is a cytotoxic agent that may cause pulmonary toxicity and therefore patients are advised to contact the doctor if cough develops. 

Concentration dependent toxicity Aminoglycosides Cytotoxic agents Ciclosporin Digoxin Lithium Tacrolimus Theophylline Warfarin... 

Utility Cytotoxic Agents with Diminished Cellular Metabolic Toxicity... 

---