Cancer cytotoxic agents

C. It is a cytotoxic agent used in the treatment of neoplastic disease, e.g. breast cancer. 

Mucopolysaccharide levels are increased in many cancer cells this increase is accompanied by a decreased vascular supply. Hyaluronidase [9001-54-17, obtained from bovine testis, dissolves the mucopolysaccharides surrounding a tumor, thereby allowing cytotoxic agents to penetrate the neoplasm with enhanced faciUty. In clinical studies hyaluronidase was given to patients with malignant tumors, alone or in combination with 5- uorouracil [51-21-8], significant decreases in tumormass were observed (55). 

There are a number of reasons for expecting multi-targeted cancer therapy to be superior to targeted cancer therapy focused on a single target or to classical, nonselective cytotoxic agents. 

Platinum complexes are cytotoxic agents yet the paradigm in cancer chemotherapy has moved to a more targeted approach, with special emphasis on signaling pathways. In this respect a remarkable story is that of arsenic trioxide, As203 (Trisenox, Cell Therapeutics Inc, Seattle, USA) which was approved by the FDA in September 2000 for treatment of acute promomyelo-cytic leukemia (APL) in patients who have relapsed or are refractory to retinoid and anthracycline chemotherapy. An estimated 1,500 new cases of APL are diagnosed yearly in the US, of which an... 

Wadler, S. and Schwartz, E.L., Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies A review, Cancer Res., 50, 3473, 1990. 

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). 

Cytotoxic agents for treatment of end-stage cancer patients ... 

Mueller H. Kassack M. Wiese M. Comparison of the usefulness of MTT, ATP and calcein assays to predict the potency of cytotoxic agents in various human cancer cell lines. Journal of Biomolecular Screening, 2004, 9,506-515. 

The mechanism by which the cytotoxic agents were approved is of inferest. Many were approved on fhe basis of response rafe as a surrogafe for survival (e.g., via the accelerated approval path). - Of nofe is the development of fhe cytotoxic agents, capecitabine received initial accelerated approval on the basis of fhe surrogafe endpoint of response rate in patients with refractory breast cancer. This was later followed up with a randomized Phase 111 trial of docetaxel wifh or withouf capecifabine in patienfs with refractory breast cancer with this trial demonstrating an improvement in survival for the combination of docetaxel + capecitabine vs. docetaxel alone. ... 

Cytotoxic agents Since proliferation of cells is essential for the immune response, agents that inhibit DNA synthesis have been used as immunosuppressive agents for many years. The first were used in the 1960s, particularly to prevent rejection of a transplanted organ, for example purine and pyrimidine analogues. These agents are not now used in autoimmune diseases but are stiU used in cancer chemotherapy (Chapter 21). 

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