The clinical pharmacology of etoposide

Article Abstract:

Etoposide has found use in the treatment of a variety of different cancers. The drug is a semisynthetic derivative of podophyllotoxin. Podophyllotoxins are found in a number of plant species, and it is interesting to note that the root of wild chervil, now known to contain deoxypodophyllotoxin, was described as a treatment for cancer in a medieval English manuscript written before 950 A.D. The drug exerts its cell-killing effects by causing breaks in DNA, and at least some of this effect is due to the drug's interaction with the enzyme DNA-topoisomerase II. This enzyme is expressed in the late S phase and G2 phase of the cell cycle, and etoposide is most effective at this time. The interaction of the drug with the enzyme is apparently reversible, and so theoretically more pronounced effects should be achieved when the drug is present for extended periods of time. Preliminary data suggests that this may indeed be the case. It is certain that the optimal therapeutic benefits of etoposide are strongly dependent upon dose and timing. The fate of the drug within the body is still the subject of research. From 30 to 50 percent of the drug is can be recovered unchanged in the urine, and the urine may contain an additional 20 percent in the form of metabolites of the drug. Different researchers do not agree on accounting for the remaining 30 percent or so, but it is clear that the drug does not accumulate in the body and that there is no hazard of cumulative toxicity with extended treatment regimens. Etoposide is not freely soluble in water solutions, and so the intravenous administration of the drug is a complex affair. An additional complication is that, once dissolved, the drug is only stable for a matter of hours. Current research estimates that about half of the etoposide in oral capsules becomes available as active drug in the bloodstream, although, again, this seems to vary widely among individuals. Even at high concentrations, etoposide is not found in appreciable concentrations in the cerebrospinal fluid, indicating that it does not cross the blood-brain barrier into the central nervous system, and is therefore useless in the treatment of tumors within the brain. The author ends his review of the pharmacology of etoposide with a quote from an authority who said, in 1982, ''in the next few years, all potentialities of the drug will be more exactly defined.'' It is now almost a decade later, and much remains to be learned. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Physiological aspects, Podophyllotoxin

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Etoposide in the management of metastatic breast cancer

Article Abstract:

While the introduction of etoposide as a chemotherapeutic agent has enhanced the treatment of several forms of cancer, no study has yet convincingly demonstrated a role for the drug in the treatment of breast cancer. A trial of the drug as a single second agent for breast cancer patients who have failed initial treatment resulted in a disappointing 6.6 percent overall response rate. Numerous studies have attempted to evaluate the effectiveness of etoposide used in combination with conventional drug regimens, but no striking results have been observed. This is true even of the combination of cisplatin and etoposide, which has been so effective in the treatment of some other cancers. Although even in cases of metastatic breast cancer it seems that the combination of etoposide and cisplatin is superior to either drug individually, the results are nonetheless mediocre for metastatic breast cancer when compared with other treatment regimens. There was, however, a small trial conducted in Spain in which an overall response rate of 11 of 27 patients was attained using a combination of etoposide and cyclophosphamide. Studies of etoposide as a part of first-line chemotherapy for previously untreated metastatic breast cancer indicate that the combination of cisplatin and etoposide may be as effective as cyclophosphamide, methotrexate, and 5-fluorouracil, a standard regimen. The cisplatin/etoposide combination is no better, however, and at present the inclusion of etoposide into chemotherapeutic treatment of breast cancer should be a part of clinical research only. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Breast cancer

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