Method of reducing toxicity of anticancer agents
a technology of anticancer agents and toxicity reduction, which is applied in the direction of biocide, drug composition, peptide/protein ingredients, etc., can solve the problems of compromising the quality of life, affecting the prognosis of patient's condition and clinical outcome, and causing significant toxic effects
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example 2
[0033] Evaluation of the effects of MSC on the toxicity of irinotecan (CPT-11) in normal rats. To demonstrate the effects of MSC on irinotecan induced toxicity in another species, rats were administered orally with 1 mg / kg / rat daily for 18 days with the first dose administered 14 days prior to irinotecan treatment. In the treated group, irinotecan was administered by i.v. push once a day for three (3) days. The results are shown in FIG. 2.
[0034] The data in FIG. 2 is a summary of the survival results obtained in two experiments using four (4) rats per group demonstrating the protective effects of MSC. A protective effect of MSC was observed when the concentration of irinotecan was increased to 200 mg / kg / day for three (3) days (twice the MTD), wherein all the animals in the group administered irinotecan alone died, only 50% of the animals died in the group administered MSC plus irinotecan.
example 3
[0035] Evaluation of the effects of MSC on the toxicity of irinotecan in tumor bearing animals. To demonstrate the effect of MSC on the antitumor activity of chemotherapy, nude mice bearing transplantable squamous cell carcinoma of the head and neck (A253) were transplanted subcutaneously (s.c.) with tumor fragments and drug treatments were initiated when tumor sizes approach about 200 mg in size. Irinotecan was administered at 100 times maximum tolerated dose (MTD), 200 or 300 mg / kg / wk for four (4) weeks representing two (2) and three (3) times the MTD, respectively in the presence or absence of MSC 0.2 mg / mouse / day. MSC was administered for 42 days and irinotecan was administered after the first 21 days of the MSC treatment. The results are presented in Table 1.
1TABLE 1 Antitumor Activity of Irinotecan by Methylselenocysteine (MSC) in Xenographts Bearing Transplantable Sequamous Cell Carcinoma of the head and neck (A253) Response Rate (%) Treatment* PR CR Survivors (%) Irinotecan ...
example 4
[0037] Evaluation of effects of selenium on the toxicity of Chemotherapeutic agents To demonstrate that the effect of selenium in reducing toxicity is not limited to irinotecan, the effects of selenium on toxicity induced by Taxol, FU, and cisplatin was evaluated in normal nude mice. Except for the weekly schedule of irinotecan, taxol (75 mg / kg), 5-FU (150 mg / kg) and cisplatin (15 mg / kg) were administered once via the intravenously route. In all cases drug doses used were toxic and above the maximum tolerated dose. The results are shown in FIG. 3. For each chemotherapeutic agent, a protective effect of MSC was observed on the survival rate of animals. Thus, these data indicate the general applicability of selenium as modulator of host toxicity induced by chemotherapeutic agents. It is important to note that chemotherapeutic agents used herein represent different classes of anticancer drugs, i.e., a topoisomerase I inhibitor (irinotecan); a DNA synthesized inhibitor (FU); a microtubu...
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