Article Abstract:
Relapse of ovarian cancer continues to pose significant difficulties for the clinician, and most attempts at chemotherapeutic salvage have proved disappointing. Cisplatin has been shown to have some effect, and since there is considerable evidence to suggest synergy between cisplatin and podophyllotoxins, these latter drugs have generated some interest. The podophyllotoxins such as etoposide and teniposide are chemical derivatives of the naturally occurring compound podophyllin. Their use in the salvage therapy of patients with ovarian cancer has been evaluated in several studies, but the results have been highly variable, with response rates ranging from 0 to 40 percent. Several avenues of research continue to show promise, however. Bone marrow suppression is the major toxic side effect of etoposide, which otherwise is relatively well tolerated. This makes etoposide a prime candidate for use in high doses in combination with bone marrow transplantation. Etoposide and teniposide are also candidates for intraperitoneal use. Intraperitoneal injection delivers a chemotherapeutic dose to abdominal cancers without the adverse effects of high drug doses circulating in the blood. However, the full advantage of intraperitoneal injection may go beyond this. The binding of the drugs to proteins tends to reduce their effectiveness; therefore, podophyllotoxins in the high-protein environment of the blood plasma are at a disadvantage from the start to drugs in the peritoneal cavity. While some preliminary results are encouraging, several studies of the intraperitoneal use of combination chemotherapy including etoposide or teniposide and a platin derivative are still in progress and the final results have not yet been tabulated. Until further research is complete, the use of etoposide and teniposide is appropriate only for the salvage treatment of patients with ovarian cancer who have already failed therapy with standard drug combinations. (Consumer Summary produced by Reliance Medical Information, Inc.)
User Contributions:
Comment about this article or add new information about this topic:
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.)
User Contributions:
Comment about this article or add new information about this topic:
Article Abstract:
At least some of the cytotoxic (cell-destroying) effects of etoposide result from the interaction of the drug with the enzyme DNA topoisomerase II. The interference of the drug with the enzyme's normal function results in breaks in the DNA strands. This enzyme is most active in the G2 phase of the cell cycle, and thus it would be expected that the action of etoposide would be dependent upon the phase of the cell cycle as well. Furthermore, pharmacologic considerations suggest that the constant presence of etoposide may enhance the drug's action, and so it was not surprising when studies of etoposide in the clinic revealed that the effectiveness of the drug was strongly dependent upon both dose and schedule. It is easier more convenient to maintain drug levels in the blood over an extended period of time if the drug can be safely administered orally. Therefore, studies have been undertaken in which patients took oral etoposide over a period of 21 days, far longer than the three- to five-day schedules of most chemotherapeutic regimens. A variety of different cancers have been treated in this manner, including small cell lung cancer, non-Hodgkin's lymphomas, germ cell tumors, and ovarian cancer. The results have revealed that among types of cancers which are known to be susceptible to etoposide, chronic oral etoposide may be superior to intravenous etoposide. Furthermore, cases were observed in which the original tumor was refractory to cisplatin and intravenous etoposide but a response could be achieved with oral etoposide, suggesting that the activity of oral etoposide may be quite distinct from that when given intravenously. The encouraging results suggest that oral etoposide in combination with other chemotherapeutic agents should be evaluated in the treatment of a variety of cancers. (Consumer Summary produced by Reliance Medical Information, Inc.)
User Contributions:
Comment about this article or add new information about this topic: