Cytotoxic agents side effects

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. 

Patients receiving cytotoxic chemotherapy very often need concomitant administrating of antiemetic therapy. Such protocols will start well in advance of administering the cytotoxic, and last for a reasonable time with regard to pharmacokinetics of the antineoplastic agent. In addition, side effects of antineoplastic therapy are made better tolerable by supportive care. 

An important advance in this field has been made by the discovery of selective serotonin (5-HT3) receptor antagonists that are effective inhibitors of cytotoxic drug-induced emesis in laboratory animals. The new agents have been found to be free of the undesirable side-effects associated with dopaminergic blockade and have shown significant protection from emesis in early clinical trials. 

Podophyllotoxin is an aryltetralin lignan which has been isoiated from severai plants of the Podophyllum species, it is a potent cytotoxic agent against various cancer celi iines, stopping the cell cycle in metaphase through the inhibition of microtubules assembly by binding the colchicine site of the tubulin [112]. Because of numerous side effects, podophyllotoxin cannot be used as a drug. 

The major classes of immunosuppressive drugs employed in clinical practice to avoid tissue rejection include calcineurin inhibitors, target of rapamycin (TOR) inhibitors, sphingosine-1 -phosphate receptor (S1P-R) modulators, cytotoxic agents, glucocorticoids and monoclonal antibodies. These drugs need to be used on a lifelong basis and have major undesirable side effects. 

Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and muagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented... 

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