A randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer

Article Abstract:

Etoposide has been repeatedly shown to be active against small cell lung cancer. Since etoposide and cisplatin combine for synergistic activity, this combination is often used in the treatment of small cell lung cancer, where overall response rates of 64 to 88 percent are observed among previously untreated patients and rates of 27 to 58 percent are observed among patients who have failed previous therapy. Research on animals has established that the effectiveness of etoposide is strongly dependent upon the level and schedule of dosage; many current regimens administer the drug over a three- to five-day period. A study was undertaken to determine the effectiveness of an oral regimen of etoposide in the treatment of small cell lung cancer. A total of 83 patients were stratified according to extent of disease, age, sex, and performance status; they were then randomly assigned to groups receiving either cisplatin plus oral etoposide or cisplatin plus intravenous etoposide. The overall response rate for the patients receiving the oral drug was 50 percent while the overall response rate for the intravenous group was 59 percent. This difference was not statistically significant, although it should be mentioned that with the small number of patients in this study, any difference less than 25 percent is unlikely to be truly meaningful. The median duration of the response was 6.1 months and 6.9 months for the oral and the intravenous groups, respectively. The toxic side effects of the chemotherapy were generally comparable between the two groups, although moderate to severe anemia was more common among the patients receiving intravenous treatment, and this group therefore required more transfused blood. The results of the study indicated that until the results of larger studies indicate otherwise, oral etoposide may be used as an effective substitute when intravenous etoposide may not be suitable. (Consumer Summary produced by Reliance Medical Information, Inc.)

Lung cancer

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Etoposide therapy for testicular cancer

Article Abstract:

Prior to the 1970s, it was uncommon for patients with advanced cancer of the testes to achieve a sustained complete response to chemotherapy. This situation changed dramatically with the introduction of the PVB treatment regimen, consisting of cisplatin, vinblastine, and bleomycin. With the PVB regimen durable complete responses can be obtained in 75 percent of the patients. Unfortunately, there was no effective treatment for the patients who failed this initial therapy. After the introduction of etoposide it was shown that partial responses could be achieved among these patients with this agent, but durable complete responses did not occur. It was discovered, however, that although neither cisplatin nor etoposide could induce sustained complete responses among patients who had failed initial therapy, the combination of the two drugs could induce such responses. In one clinical trial, 38 percent of the patients who had failed initial therapy remained disease-free after treatment with cisplatin and etoposide. Considering these successes, it was only natural that etoposide would be incorporated into regimens designed for initial treatment and not salvage therapy. Researchers found that the replacement of vinblastine with etoposide in the PVB regimen produced responses as good as those obtained with PVB if not better. The major advantage turned out to be a significant reduction in adverse side effects. Since the success is at least as good, and the side effects less severe, the combination of etoposide, cisplatin, and bleomycin has become the standard treatment for disseminated testicular cancer. New trials examining the effects of different treatment schedules and the use of oral etoposide may extend these improvements in chemotherapy even further. (Consumer Summary produced by Reliance Medical Information, Inc.)

Testicular cancer

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Future directions for etoposide therapy

Article Abstract:

Since its introduction in 1971, etoposide has become an important part of the chemotherapeutic regimens for several cancers, most notably small cell lung cancer, germ cell tumors, and intermediate- and high-grade (advanced) non-Hodgkin's lymphomas. Despite its successes, there is every reason to believe that further improvements in the application and use of this drug lie in the future. Etoposide seems to be especially sensitive to the dose and schedule of its administration, giving researchers many variables to adjust while seeking the greatest effectiveness. Furthermore, preliminary data suggest that it may be both more effective and less toxic to administer oral doses of etoposide over a long period of time. If these data are confirmed, then many of the chemotherapeutic protocols already successfully using etoposide may be reevaluated for chronic oral etoposide as well. Despite careful pharmacological studies, however, there is much to be learned about the action of etoposide. It is not yet known, for example, what levels of the drug should be maintained for effective anticancer activity. While clinical studies had averaged at least 1.0 microgram per milliliter of blood, greater understanding of the disposition of the drug within the body should permit achieving maximum therapeutic benefit while maintaining toxicity at an acceptable level. (Consumer Summary produced by Reliance Medical Information, Inc.)

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