Cancer chemotherapy other treatments

Several non-peptide small molecule compoimds from Merck, Schering-Plough, Bristol-Myers Squibb, and Janssen are in phase I clinical trials for the treatment of cancer. This has bolstered the significance of this approach of cancer chemotherapy. Other organizations that have ongoing active FPTase inhibitor programs include Abbott, Rhone Poulenc Rorer, Parke- Davis, Pfizer, Zeneca, Eisai and Biomeasure. While several review articles have recently been published that cover various aspects of FPTase inhibitors [25-28,31,60,61], the discussion of FPTase inhibitors derived from natural products is limited. Therefore, this article will not be an extensive review of the literature dealing with chemically derived inhibitors of farnesyl-protein transferase. Rather, it will focus on inhibitors of famesyl-protein transferase that have been identified from natural product sources discovered by Merck or other institutions. 

Dronabinol is indicated for the treatment of the nausea and vomiting produced by cancer chemotherapy in patients who have failed to respond adequately to other conventional treatments. This agent may be habit forming and can be expected to produce disturbing psychomimetic reactions. It should only be used under close supervision. 

Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that postsurgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. 

An example of a simple CZE method for peptide analysis and characterization is the one developed for protegrin IB-367.37 IB-367 is a peptide containing 17 amino acid residues that possess antimicrobial properties, and it is being developed for treatment of oral mucositis associated with aggressive cancer chemotherapy as well as other topical applications. This polycationic product was chemically synthesized using solid-phase and purified by preparative reversed-phase HPLC. IB-367 is rich in cysteine and arginine residues. 

There are several possible reasons for the negative results of this trial. One possibility is that an insufficient amount of chemotherapy was administered. Few would argue that two cycles of chemotherapy is likely insufficient to eradicate microscopic metastatic disease. However, in a 975 patient trial conducted by the Medical Research Council and the European Organization for the Research and Treatment of Cancer, three cycles of CMV given prior to definitive therapy failed to provide the 10% improvement in survival that could have been detected by the trial (43). Similarly, other trials of neoadjuvant chemotherapy to date have similarly not shown any obvious improvement in survival (70-739, so it is unlikely that the number of cycles of therapy here had a significant impact on the outcome of the study. Even if more cycles could have had an impact, it should be remembered that this trial was stopped early because of chemotherapy-related treatment deaths with only two cycles of treatment. Others... 

As mentioned, interferons also help control abnormal cell proliferation, and these drugs have been approved for use in certain cancers. Interferons are often used as part of the treatment for certain leukemias, lymphomas, and several other forms of cancer (see Table 34-4). Interferon use in cancer chemotherapy is discussed in more detail in Chapter 36. 

Cancer chemotherapy is only one method of treating neoplastic disease. The other primary weapons in the anticancer arsenal are surgery and radiation treatment.18,61 The choice of one or more of these techniques depends primarily on the patient, the type of cancer, and the tumor location. In many situations, chemotherapy may be the primary or sole form of treatment in neoplastic disease, especially for certain advanced or inoperable tumors, or in widely disseminated forms of cancer, such as leukemia or lymphoma.6 In other situations, chemotherapy is used in combination with other techniques, such as an adjuvant to surgery and radiation treatment.18,27 Primary examples of adjuvant cancer chemotherapy include using anticancer drugs following a mastectomy or surgical removal of other carcinomas.19,54,43,61... 

One of the most important roles for effective cancer chemotherapy is as an adjuvant to initial or primary field treatment with other methods such as surgery or radiation therapy. Failures with primary field therapy are due principally to occult micrometastases outside the primary field. With the currently available treatment modalities, this form of combined-modality therapy appears to offer the greatest chance of curing patients with solid tumors. 

Other organoarsenicals, most notably lewisite (dichloro[2-chlorovinyl]arsine), were developed in the early twentieth century as chemical warfare agents. Arsenic trioxide was reintroduced into the United States Pharmacopeia in 2000 as an orphan drug for the treatment of relapsed acute promyelocytic leukemia (Chapter 55 Cancer Chemotherapy). 

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