Antineoplastic drugs types

Adjuvant chemotherapy involves the use of antineoplastic drugs when surgery or radiation therapy has eradicated the primary tumor but historical experience with similar patients indicates a high risk of relapse due to micrometastases. Adjuvant chemotherapy should employ drugs that are known to be effective in the treatment of advanced stages of the particular tumor being treated. Adjuvant chemotherapy has played a major role in the cure of several types of childhood cancers as well as breast cancer, colorectal cancer, and osteosarcoma in adults. 

The antineoplastic drug streptozotocin is capable of inducing type 1 (insulin-dependent) diabetes when administered (intraper-itoneally) at low doses on six consecutive days. Important to note is that a strong dependency on strain and/or sex has been observed, with male C57BL/Ks (H2d) mice most sensitive (Leiter, 1982 Herold et al., 1996). Streptozotocin appeared to elicit a typical Thl-... 

An interesting example of a DDI due to the inhibition of a non-CYP enzyme that can have serious clinical consequences is the inhibition of xanthine oxidase by allopu-rinol 6-mercaptopurine (6-MP) as an antimetabolite type of antineoplastic drug. One of its indications is in the treatment of inflammatory bowel disease. Actually, 6-MP is a prodrug whose active metabolite, 6-thiogua-nine (6-TG) is responsible for its therapeutic activity. Some nonresponders to 6-MP do not form sufficient amounts of 6-TG. A complementary pathway of 6-MP metabolism is oxidation to 6-thiouric acid (6TU), which is mediated by xanthine oxidase. Inhibition of this complementary pathway by allopurinol shunts the metabolism of 6-MP favoring increased formation of 6-TG. 

We will consider here this problem in the context of cancer chemotherapy. Since antineoplastic drugs by necessity are quite toxic, it would seem that meaningful mathematical models could be important guides in the optimization of various types of experimental and clinical trials. The mode of action of many of these drugs, at least semiempirically, is qualitatively and sometimes quantitatively known, and the pharmacokinetics of several types have been studied. More specific information seems to be available concerning the action on tumor cells than toxicity in critical normal cells such as bone marrow and gastrointestinal tract. However, to be useful in a clinical sense, both effects must be predictable since successful therapy is based on the balance between the cancer cell death and the toxicity. 

Care of the patient receiving an antineoplastic drug depends on factors such as the drug or combination of dru given, the dos e of the dru, tlie route of administration, the patient s physical response to tlierapy, the response of the tumor to chemotlierapy, and tlie type and severity of adverse reactions. Some dru may be administered by various rout, depending on tlie cancer being treated. Fbr example tliiotepa may be administered by the intravenous route for breast cancer, intravesical route for superficial bladder cancer, intrapleural route for malignant pleural effusions, and by tlie intraperitoneal route for ovarian cancer. 

Gebelein and coworkers have prepared monomers and polymers based on the antineoplastic agents 5-fluorouracil and 6-mercapto-purine (26). These polymers would be potentially useful in treating various types of cancer or leukemia and some derivatives have shown biological activity. Previous work by this group has Included the synthesis of polyisoprene derivatives containing sulfa drug, carbamate, urea, oxazolldone and oxazole units (27.28). 

It is obvious that this approach using nucleic bases can lead to antineoplastic polymers since several such systems have shown this activity (34,45,46,48). This is not totally unexpected since the nucleic base derivatives 5-fluorouracll and 6-mercaptopurlne are antineoplastic agents. The polymers of this type made to date have been either the Insoluble type or the soluble type polymeric drug systems. This approach should be especially effective if some directing group is also put into these polymers to carry them selectively into tumorous tissue. Research along this line is in progress in our laboratories and some other places as well. 

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