Asbestos Cancer Update 2010

In 1948, Dr. Sidney Farber showed that a folic acid analog could induce remission in childhood leukemia. Approximately 10 out of the 16 patients treated demonstrated evidence of hematologic improvement. This experience provided the foundation for scientists to synthesize a number of other agents that either target naturally occurring compounds or inhibit key enzymatic reactions in their biochemical pathways. In general, all antimetabolites interfere with normal metabolic pathways, including those necessary for making new DNA. The most widely used antifolate in cancer therapy, with activity against leukemia, lymphoma, breast cancer, head and neck cancer, sarcomas, colon cancer, bladder cancer and choriocarcinomas, is Methotraxate. Methotraxate inhibits a crucial enzyme required for DNA synthesis and therefore exerts its effect on the S phase of the cell cycle.

5-Fluorouracil (5-FU), another widely used antimetabolite, prevents DNA synthesis by interfering with the nucleotide ( DNA components) production. It, too, has a wide range of activity including colon cancer, breast cancer, head and neck cancer, pancreatic cancer, gastric cancer, anal cancer, esophageal cancer and hepatomas (primary liver tumor). A unique and interesting aspect of this drug is its toxicity profile. 5-Fluorouracil is metabolized by a naturally occurring enzyme in the body called dihydropyrimidine dehydrogenase, or DPD. There is a small population of people who are deficient of this particular enzyme. Lacking DPD does not interfere with normal body function and thus people are not aware that they are lacking it. However, when these patients are given this chemotherapy drug, they are unable to metabolize it and therefore get acute and severe toxicities (side effects). The most often seen toxicities include bone marrow suppression, severe GI toxicities, and neurotoxicities which may include seizures and even coma. It is important for the oncologist to recognize this early and give the patient Thymidine as an antidote. A drug called Capecitabine is an oral type of 5-Fluorouracil compound that has similar side effect potentials.

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The goal of all chemotherapy drugs is to kill the cancerous cells, while using a dose that causes the least harm the body’s healthy cells. To achieve this goal, scientists tried to identify characteristics that are unique to cancer cells and are not found on normal tissue. A distinct cancer cell trait could serve as a potential target for a chemotherapy drug and thereby spare normal tissues. One feature that is seen in most cancer cells is that they grow at a rate faster than normal cells. Therefore, targeting some aspect of the cell growth cycle seems reasonable. Fast-growing cells would be affected the most and slow-growing cells would be least disturbed. In fact, that is the basis for many chemotherapy agents. This is apparent when considering the side effect profiles of most chemotherapy drugs. Hair follicles, skin, and the cells that line the gastrointestinal tract are some of the fastest growing cells in the human body, and therefore are most sensitive to the effects of chemotherapy. It is for this reason that patients may experience hair loss, rashes, and diarrhea, respectively.

The human body processes and excretes all drugs through either the liver or the kidneys. Therefore, when a patient has kidney or liver damage, giving chemotherapy becomes precarious. Administering the recommended amount of drug may prove to be too toxic in a patient unable to metabolize and excrete it. The pharmacokinetics (how the body handles a drug) for cancer patients are very complex, and chemotherapy pharmacology is a subspecialty on its own. Unfortunately, kidney and liver damage often result due to cancer invasion, possibly limiting the patient’s chemotherapy options.

Pharmacokinetics is further complicated in cancer patients, as they are often taking multiple medications, some of which have overlapping metabolic pathways and side effect profiles. An example of this difficult situation is in the brain cancer patient. Because brain tumors often present with seizures, many of these patients take anti-seizure medications. Anti-seizure medications are metabolized by the liver and affect the metabolism of many chemotherapy drugs. Dose adjustments are an absolute necessity to avoid toxicities or sub-therapeutic dosing (doses that are too low) in these patients.

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Chemotherapy, or the use of chemical agents to destroy cancer cells, is a mainstay in the treatment of malignancies. The possible role in treating illness was discovered when the bone marrow suppressive effect of nitrogen mustard was noted in the early 1900’s. Since that time, the search for drugs with anticancer activity has continued, and the goal of treatment with chemotherapy has evolved from relief of symptoms to cancer cure. A major advantage of chemotherapy is its ability to treat widespread or metastatic cancer, whereas surgery and radiation therapy are limited to treating cancers that are confined to specific areas.

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Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

OBJECTIVE: The objective of this study was to improve the treatment results for locally advanced tongue cancer. A combination of radiotherapy with continuous intra-arterial therapy using CBDCA was used. STUDY DESIGN: According to TNM staging (1997), 29 patients had stage III lesions and 11 patients had stage IV (M0) lesions. A catheter was inserted through the lingual artery in 26 patients, through the external carotid artery in 11 patients, and through the faciolingual trunk in 2 patients. CBDCA was continuously infused for 4 to 6 weeks. With IA chemotherapy, external irradiation (median dose: 46.8 Gy) was simultaneously performed, and 1 to 2 courses of systemic chemotherapy were performed in 19 patients before intra-arterial chemotherapy. RESULTS: The 5-year local control rate was 65%. The 5-year OS rate was 39.5%. There were no clinically significant adverse side effects. CONCLUSION: Continuous IA CBDCA and concurrent radiation therapy can be delivered safely with good efficacy for locally advanced carcinoma of the tongue.

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Department of Radiation Oncology, Trakya University, Faculty of Medicine, Edirne, Turkey.

Cerebrovascular disease is common in cancer patients. Some tumors are at high risk for cerebrovascular complications. The development of cerebrovascular disease may be provoked by cancer treatment. No well-planned prospective studies about other causes of thrombosis are available, although various case reports about thrombosis related to chemotherapy have been published. L-asparaginase, cisplatin, 5-fluorouracil (5-FU) and methotrexate are anticancer agents which are reported to relate to stroke. The mechanisms by which antineoplastic agents may lead to stroke include endothelium toxicity and abnormalities of coagulation factors. Also, brain hemorrhages that could result from chemotherapy effects on the hemostatic system were reported. Besides, it is difficult to determine whether stroke is caused by chemotherapy or cancer itself. Clinicians deal not only with problems originating from cancer itself, but also with the complications resulting from its treatment. Treatment-induced cerebrovascular disorders affect quality of life and survival in cancer patients. For this reason, cancer treatment should be planned by taking into consideration the possibility of cerebrovascular complications.

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