Chemotherapeutic agents cyclophosphamide

Metabolism of the important cancer chemotherapeutic agent cyclophosphamide (Cytoxan) follows a hydroxylation pathway similar to that Just described for cyclic amides. This drug is a cyclic phosphoramide derivative and, for the motit part, is the phosphorous counterpart of a cyclic amide. Because cyclophosphamide itself is pharmacologically inac-... 

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. 

Importantly, the toxicity of bleomycin is cumulative. Total doses in excess of 450 units are associated with a significantly increased incidence of adverse lung reactions and death. The incidence of bleomycin-induced lung toxicity has been reported between 0% and 46% with a mortality rate of 3% (5,7). As mentioned above, high cumulative dose, extreme of age, uremia, the use of supplemental oxygen, and radiation therapy are well-documented risk factors for bleomycin toxicity. Other chemotherapeutic agents (cyclophosphamide and vincristine) may also have a synergistic effect with bleomycin. Finally, bleomycin may occasionally reactivate a prior radiation-induced pneumonitis, a phenomenon known as radiation-recall. ... 

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

I 10. The answer is a. (Hardman, p 1302J Cyclophosphamide is classified as a poly functional alkylating drug that transfers its alkyl groups to cellular components. The cytotoxic effect of this agent is directly associated with the alkylation of components of DNA. Methotrexate and 5-FU are classified as anti metabolites that block intermediary metabolism to inhibit cell proliferation. Tamoxifen is an antiestrogen compound. Doxorubicin is classified as an antibiotic chemotherapeutic agent. 

Neutropenia is a condition characterized by a decrease in blood neutrophil count below 1.5 X 109 cells per litre a normal blood count is (2.0-7.5) X 109 cells per litre. Its clinical symptoms include the occurrence of frequent and usually serious infections, often requiring hospitalization. Neutropenia may be caused by a number of factors (Table 10.6), at least some of which are responsive to CSF treatment. Particularly noteworthy is neutropenia triggered by administration of chemotherapeutic drugs to cancer patients. Chemotherapeutic agents (e.g. cyclophosphamide, doxorubicin and methotrexate), when administered at therapeutically effective doses, often induce the destruction of stem cells and/or compromise stem cell differentiation. 

Herceptin with cisplatin, doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel. A comparison of serum levels of trastuzumab given in combination with various chemotherapeutic agents did not suggest the possibility of any pharmacokinetic interactions except in combination with paclitaxel. Although not statistically signihcant, mean serum trough concentrations of trastuzumab were consistently elevated, about 1.5-fold, when Herceptin was administered in combination with paclitaxel. However, trastuzumab and paclitaxel were used concurrently in clinical trials with positive outcome results. The concurrent administration of anthracyclines, cyclophosphamide, and trastuzumab increased the incidence and severity of cardiac dysfunction during clinical trials. 

High-dose therapy with certain chemotherapeutic agents, including cytosine arabinoside, cyclophosphamide, methotrexate, and 5-fluorouracil, has been implicated in conjunctivitis. However, it appears that low-dose therapy with the anticancer agent tamoxifen is infrequently associated with anterior segment toxicity. 

The potential for direct exposure exists when injecting cancer patients with N-nitroso-N-methylurea in conjunction with cyclophosphamide, as a chemotherapeutic agent. Health professionals such as pharmacists, physicians, and nurses are potentially exposed to the compound during the preparation and administration of the pharmaceuticals or during clean-up. 

Preliminary animal studies have demonstrated the possibility that scullcap may improve the tolerability and efficacy of some chemotherapeutic agents. Scutellaria baicalensis Georgi was found to decrease tumor cell viability and ameliorate myelosuppression when used with cyclophosphamide and 5-fluorouracil in both mice and rats (Razina et al., 1987). 

Cyclophosphamide is effective against acute leukemia, chronic lymphocytic leukemia and multiple myeloma. In combination with other chemotherapeutic agents it is found to cause radical cure in acute lymphoplastic leukemia in children and also in Burkitt s lymphoma. It has a positive advantage over other alkylating agents because of its activity both parenterally and orally besides its tolerance over prolonged periods in divided doses. 

TERT, telomere reverse transcriptase. Click TERT promoter mutations in skin cancer by Populo H et al. TERT promoter mutations with BRAE V600E mutation thyroid cancer by Liu X et al. TERT promoter mutations cutaneous melanoma by Heidenreich B et al. Effect of four chemotherapeutic agents, bleomycin etoposide cisplatin cyclophosphamide, on DNA damage in spermatogonial cell line by Liu M et al. 

Intravenous Chemotherapy. The most effective chemotherapeutic agent for bladder carcinoma is cisplatin with objective responses ranging from 26% to 56%, with complete responses seen in 0%-14%. In a study of 121 patients, MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin] and cisplatin) demonstrated an overall response rate of 72% one half of the responses being complete (Sternberg et al. 1989). The median survival was 13 months. CISCA (cisplatin, doxorubicin, and cyclophosphamide) was compared to MVAC MVAC proved to be superior with a difference in median survival of 82 versus 40 weeks (Logothetis... 

Several analogs of chemotherapeutic agents have been synthesized. These include paclitaxel, cyclophosphamide, 5-fluorouracil (5-FU), and others. The most widely smdied labeled chemotherapeutic agent is 5-FU, a dmg that has been used for cancer treatment for several decades. The drug inhibits DNA synthesis by inhibition of thymidylate synthase, which is in turn the key... 

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