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British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jan;69(1):191–195. doi: 10.1038/bjc.1994.33

Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.

M T Seymour 1, J L Mansi 1, C J Gallagher 1, M E Gore 1, P G Harper 1, T R Evans 1, P M Edmonds 1, M L Slevin 1
PMCID: PMC1968773  PMID: 8286205

Abstract

This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.

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Selected References

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  1. Belinson J. L., Pretorius R. G., McClure M., Ashikaga T. Hexamethylmelamine, methotrexate, 5-fluorouracil as second line chemotherapy after platinum for epithelial ovarian malignancies. Gynecol Oncol. 1986 Mar;23(3):304–309. doi: 10.1016/0090-8258(86)90130-7. [DOI] [PubMed] [Google Scholar]
  2. Benedetti Panici P., Scambia G., Greggi S., Salerno G., Cento R., Mancuso S. Doxorubicin and cyclophosphamide, alternated with bleomycin and mitomycin C as a second-line regimen in advanced ovarian carcinoma resistant to cisplatin-based chemotherapy. Oncology. 1990;47(4):296–298. doi: 10.1159/000226836. [DOI] [PubMed] [Google Scholar]
  3. Coleman R., Clarke J., Gore M., Wiltshaw E., Slevin M., Harper P. A phase II study of mitozantrone in advanced carcinoma of the ovary. Cancer Chemother Pharmacol. 1989;24(3):200–202. doi: 10.1007/BF00300244. [DOI] [PubMed] [Google Scholar]
  4. Coleman R., Towlson K., Wiltshaw E., Slevin M., Blake P., Stein R., Coombes R., Harper P. Epirubicin for pretreated advanced ovarian cancer. Eur J Cancer. 1990;26(7):850–851. doi: 10.1016/0277-5379(90)90173-q. [DOI] [PubMed] [Google Scholar]
  5. Eckhardt S., Hernádi Z., Thurzó L., Telekes A., Sopkova B., Mechl Z., Pawlicki M., Kerpel-Fronius S. Phase II clinical evaluation of etoposide (VP-16-213, Vepesid) as a second-line treatment in ovarian cancer. Results of the South-East European Oncology Group (SEEOG) Study. Oncology. 1990;47(4):289–295. doi: 10.1159/000226835. [DOI] [PubMed] [Google Scholar]
  6. Einzig A. I., Wiernik P. H., Sasloff J., Runowicz C. D., Goldberg G. L. Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma. J Clin Oncol. 1992 Nov;10(11):1748–1753. doi: 10.1200/JCO.1992.10.11.1748. [DOI] [PubMed] [Google Scholar]
  7. Greco F. A., Johnson D. H., Hainsworth J. D. Chronic daily administration of oral etoposide. Semin Oncol. 1990 Feb;17(1 Suppl 2):71–74. [PubMed] [Google Scholar]
  8. Hansen F., Malthe I., Krog H. Phase II clinical trial of VP-16-213 (etoposide) administered orally in advanced ovarian cancer. Gynecol Oncol. 1990 Mar;36(3):369–370. doi: 10.1016/0090-8258(90)90144-a. [DOI] [PubMed] [Google Scholar]
  9. Harvey V. J., Slevin M. L., Joel S. P., Smythe M. M., Johnston A., Wrigley P. F. Variable bioavailability following repeated oral doses of etoposide. Eur J Cancer Clin Oncol. 1985 Nov;21(11):1315–1319. doi: 10.1016/0277-5379(85)90310-4. [DOI] [PubMed] [Google Scholar]
  10. Hill B. T., Whelan R. D., Rupniak H. T., Dennis L. Y., Rosholt M. A. A comparative assessment of the in vitro effects of drugs on cells by means of colony assays or flow microfluorimetry. Cancer Chemother Pharmacol. 1981;7(1):21–26. doi: 10.1007/BF00258208. [DOI] [PubMed] [Google Scholar]
  11. Hillcoat B. L., Campbell J. J., Pepperell R., Quinn M. A., Bishop J. F., Day A. Phase II trial of VP-16-213 in advanced ovarian carcinoma. Gynecol Oncol. 1985 Oct;22(2):162–166. doi: 10.1016/0090-8258(85)90022-8. [DOI] [PubMed] [Google Scholar]
  12. Lee C. R., Nicholson P. W., Souhami R. L., Slevin M. L., Hall M. R., Deshmukh A. A. Patient compliance with prolonged low-dose oral etoposide for small cell lung cancer. Br J Cancer. 1993 Mar;67(3):630–634. doi: 10.1038/bjc.1993.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Manetta A., MacNeill C., Lyter J. A., Scheffler B., Podczaski E. S., Larson J. E., Schein P. Hexamethylmelamine as a single second-line agent in ovarian cancer. Gynecol Oncol. 1990 Jan;36(1):93–96. doi: 10.1016/0090-8258(90)90115-2. [DOI] [PubMed] [Google Scholar]
  14. Marzola M., Zucchetti M., Colombo N., Sessa C., Pagani O., D'Incalci M., Cavalli F., Mangioni C. Low-dose oral etoposide in epithelial cancer of the ovary. Ann Oncol. 1993 Jun;4(6):517–519. doi: 10.1093/oxfordjournals.annonc.a058565. [DOI] [PubMed] [Google Scholar]
  15. McGuire W. P., Rowinsky E. K., Rosenshein N. B., Grumbine F. C., Ettinger D. S., Armstrong D. K., Donehower R. C. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med. 1989 Aug 15;111(4):273–279. doi: 10.7326/0003-4819-111-4-273. [DOI] [PubMed] [Google Scholar]
  16. Miller J. C., Einhorn L. H. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990 Feb;17(1 Suppl 2):36–39. [PubMed] [Google Scholar]
  17. Pater J. L., Carmichael J. A., Krepart G. V., Fraser R. C., Roy M., Kirk M. E., Levitt M., Brown L. B., Wilson K. S., Shelley W. E. Second-line chemotherapy of stage III-IV ovarian carcinoma: a randomized comparison of melphalan to melphalan and hexamethylmelamine in patients with persistent disease after doxorubicin and cisplatin. Cancer Treat Rep. 1987 Mar;71(3):277–281. [PubMed] [Google Scholar]
  18. Slevin M. L., Clark P. I., Joel S. P., Malik S., Osborne R. J., Gregory W. M., Lowe D. G., Reznek R. H., Wrigley P. F. A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol. 1989 Sep;7(9):1333–1340. doi: 10.1200/JCO.1989.7.9.1333. [DOI] [PubMed] [Google Scholar]
  19. Slevin M. L. Low-dose oral etoposide: a new role for an old drug? J Clin Oncol. 1990 Oct;8(10):1607–1609. doi: 10.1200/JCO.1990.8.10.1607. [DOI] [PubMed] [Google Scholar]
  20. Sutton G. P., Blessing J. A., Homesley H. D., Berman M. L., Malfetano J. Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 1989 Nov;7(11):1672–1676. doi: 10.1200/JCO.1989.7.11.1672. [DOI] [PubMed] [Google Scholar]

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