Cyclophosphamide sensitivity

Schrier, D.J. and Phan, S.H. (1984). Modulation of bleomycin-induced pulmonary fibrosis in the BALB/c mouse by cyclophosphamide-sensitive T cells. Am. J. Pathol. 116, 270-278. 

Recurrent SCLC is usually less sensitive to chemotherapy. If recurrence is more than 6 months after induction chemotherapy, the original regimen can be repeated. If recurrence occurs in less than 6 months but >3 months, treatment options include a taxane, gemcitabine, topotecan, irinotecan, CAV (cyclophosphamide, doxorubicin, and vincristine), and vinorelbine. 

Suppression of the DTH Response The induction and regulation of CD8+ Tregs in vivo is complex and dependent on several cell types [2,3], In vivo, the induction of CD8-I- suppressor T cells required Lyt-l-l- (CD4) suppressor-inducer T cells that did not directly suppress DTH. The mechanism of this induction was not clear but appeared to be mediated by antigen-specific, soluble molecules produced by the suppressor-inducer T cells [18]. Additionally, the in vivo induction of CD8+ suppressor T cells requires cells sensitive to the cytotoxic effects of cyclophosphamide [19,20]. 

Mesna (Mesnex) [Uroprotectant/Antidote] Uses Prevent hem-orrhagic cystitis d/t ifosfamide or cyclophosphamide Action Antidote, reacts w/ acrolein and other metabolites to form stable compounds Dose Per protocol dose as % of ifosfamide or cyclophosphamide dose Oral 20% IV dose at 0, 4, 8 h (mix w/ juice) Caution [B /—] Contra Thiol sensitivity Disp Inj, tabs SE -i- BP, allergic Rxns, HA, GI upset, taste p v sion EMS Antidote for two antineoplastic drugs (ifosfamide and cyclophosphamide) OD May cause D, muscle tremors, SOB, bluish skin color, and Szs symptomatic and supportive... 

Crook TR, Souhami RL, Whyman GD, et al. 1986. Glutathione depletion as a determinant of sensitivity of human leukemia cells to cyclophosphamide. Cancer Res 46 5035-5038. 

Anticancer chemotherapies Azathioprine, cyclophosphamide, methotrexate etc. The cytotoxic substances affect proliferating cells and hematopoiesis as well as lymphocyte proliferation are especially sensitive. Association with risk of clinical infections clearly established. 1 % of chemotherapy patients develop an independent cancer within 10 years, 3 % within 20. Noteworthy, some anticancer drugs are now used also as immunosuppressant for autoimmune diseases... 

Gorbacheva VY, Kondratov RV, Zhang R, et al. Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK/BMALl transactivation complex. Proc Natl Acad Sci USA 2005 102 3407-12. 

Delon, A. Favreliere, S. Couet, W. Courtois, P. Bouquet, S. Rapid and sensitive determination of thalidomide in human plasma hy high-performance liquid chromatography. J.Liq.Chromatogr., 1996, 18, 297—309 [SPE ciprofloxacin is IS simultaneous acyclovir, azathioprine, cefotaxime, ceftazidime, flucytosine, metronidazole non-interfering amphotericin, clobazam, clonazepam, cyclophosphamide, cyclosporin, diazepam, diltiazem, hydro zine, nifedipine, prednisolone]... 

COMBINATION THERAPY Higher response rates are seen when 5-FU is used in combination with other agents, such as cyclophosphamide and methotrexate (breast cancer), cisplatin (head and neck cancer), and with oxaliplatin or irinotecan in colon cancer. The combination of 5-FU and oxaliplatin or irinotecan has become the standard first-hne treatment for patients with metastatic colorectal cancer. The use of 5-FU in combination regimens has improved survival in the adjuvant treatment for breast cancer, and with oxaliplatin and leucovorin, for colorectal cancer. 5-FU also is a potent radiation sensitizer. Beneficial effects also have been reported when combined with irradiation for cancers of the esophagus, stomach, pancreas, cervix, anus, and head and neck. 5-FU is used widely with very favorable results for the topical treatment of premalignant keratoses of the skin and multiple superficial basal cell carcinomas. 

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