Breast Cancer Research and Treatment

, Volume 34, Issue 2, pp 185–189 | Cite as

Second-line chemotherapy with long-term low-dose oral etoposide in patients with advanced breast cancer

  • M. Bontenbal
  • A. S. Th. Planting
  • J. Verweij
  • R. de Wit
  • W. H. J. Kruit
  • G. Stoter
  • J. G. M. Klijn
Brief communication

Summary

In a phase II study, 27 patients with metastatic breast cancer were treated with oral etoposide as second-line chemotherapy at a dose of 50 mg/m2/day for 21 days, which courses were repeated every 4 weeks. Twenty-one patients were evaluable for response, and twenty-five for toxicity. In two (10%) patients a partial response was observed with a duration of 60 and 122 weeks respectively, and seven patients (33%) showed stable disease. Gastrointestinal toxicity was usually mild, though relatively frequent. Anemia grade II and III was observed in 20% of all courses (< 10% of all measurements), and leukopenia grade III and IV was observed in 22% of all courses (< 10% of all measurements). There was one toxic death.

Reviewing the literature we calculated a response rate of intravenous etoposide treatment of 8% in 276 patients with metastatic breast cancer from 7 studies (response rates ranging between 0–14%), while (chronic) oral treatment caused a response rate of 19% in 145 patients from 8 different studies (response rates ranging between 0–35%).

Key words

breast cancer oral etoposide phase II 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Henderson IC, Allegra JC, Woodcock Thet al.: Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol 7: 560–571, 1989Google Scholar
  2. 2.
    Clark PI, Slevin ML: The clinical pharmacology of etoposide and teniposide. Clin Pharmacokin 12: 223–252, 1987Google Scholar
  3. 3.
    Slevin ML, Clark PI, Joel SPet al.: A randomized trial to evaluate the effect of schedule on the activity of etoposide in small cell lung cancer. J Clin Oncol 9: 1333–1340, 1989Google Scholar
  4. 4.
    D'Incalci M, Erba E, Vaghi Met al.:In vitro cytotoxicity of VP16 on primary tumour and metastasis of Lewis lung carcinoma. Eur J Cancer Clin Oncol 18: 377–380, 1982Google Scholar
  5. 5.
    Hill BT, Whetan RDH, Rupniak HTet al.: A comparative assessment of thein vitro effects of drugs on cells by means of colony assays on flow microfluorimetry. Cancer Chemother Pharmacol 7: 21–26, 1982Google Scholar
  6. 6.
    Comis RL: Oral etoposide in oncology: an evolving role. Ann Oncol 3: 63–67, 1992Google Scholar
  7. 7.
    Sledge GW: Etoposide in the management of metastatic breast cancer. Cancer 67: 266–270, 1991Google Scholar
  8. 8.
    Hainsworth JD, Johnson DH, Frazier SR, Greco FA: Chronic daily administration of oral etoposide. A phase I trial. J Clin Oncol 7: 396–401, 1989Google Scholar
  9. 9.
    Miller JC, Loehrer PJ, Williams SD, Einhorn LH: Phase II study of oral VP-16 in refractory germ cell tumors. Proc ASCO 8: 145, 1989Google Scholar
  10. 10.
    Cavalli F, Jungi WF, Brunner KW: Randomisierte Phase II Studie mit VP-16-213 (Etoposide) in der Behandlung vom fortgeschrittenen Mammakarzinom. Onkologie 4: 80–83, 1981Google Scholar
  11. 11.
    Vaughn CB, Panettiere F, Thigpen T, Bottomley R, Hoogstraten B, Samal B: Phase II evaluation of VP-16-213 in patients with advanced breast cancer: A Southwest Oncology Group study. Cancer Treat Rep 65: 443–445, 1981Google Scholar
  12. 12.
    Schell FC, Yap HY, Hortobagyi GN, Esparza L: Phase II study of VP16-213 (Etoposide) in refractory metastatic breast carcinoma. Cancer Chemother Pharmacol 7: 223–225, 1982Google Scholar
  13. 13.
    Nissen NI, Pajak TF, Leone LA, Bloomfield CD, Kennedy BJ, Ellison RR, Silver RTet al.: Clinical trial of VP 16-213 (NSC 141540) i.v. twice weekly in advanced neoplastic disease. A study by the Cancer and Leukemia Group B. Cancer 45: 232–235, 1980Google Scholar
  14. 14.
    Ahmann DL, Bisel HF, Eagan RT, Edmonson JH, Hahn RG, O'Connell MJ, Frytak S: Phase II evaluation of VP-16-213 (NSC-141540) and Cytembena (NSC-104801) in patients with advanced breast cancer. Cancer Treat Rep 60: 633–635, 1976Google Scholar
  15. 15.
    Eagan RT, Ahmann DL, Bisel HF: Evaluation of VP-16 and the combination of Adriamycin and Vincristine in advanced breast cancer. Oncology 33: 146–148, 1976Google Scholar
  16. 16.
    Fraschini G, Esparza L, Holmes F, Tashima C, Theriault R, Hortobagyi G: High-dose Etoposide in metastatic breast cancer. (Abstr). Breast Cancer Res Treat 14: 142, 1989Google Scholar
  17. 17.
    Falkson G, van Deyk JJ, van Eden EB, van der Merwe AM, van den Bergh JA, Falkson HC: A clinical trial of the oral form of 4′-demethyl-epipodophyllotoxin-β-D ethylidene glucoside (NSC 141540), VP 16-213. Cancer 35: 1141–1144, 1975Google Scholar
  18. 18.
    Palombo H, Estapé J, Viñolas N, Grau JJ, Mañé JM, Daniels M, Mellado B: Chronic oral Etoposide in advanced breast cancer. Cancer Chemother Pharmacol 33: 527–529, 1994Google Scholar
  19. 19.
    Martin M, Lluch A, Casado A, Santabarbara P, Adrover E, Valverde J, Lopez-Martin J, Rodriguez-Lescure A, Azagra P, Garcia-Conde J, Diaz-Rubio E: Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer. J Clin Oncol 5: 986–991, 1994Google Scholar
  20. 20.
    Calvert AH, Lind MJ, Millward MM, Cantwell BMJ, Gumbrell L, Proctor M, Simmons D, Chapman F, Robinson A, Charlton C, Balmanno K, Newell D: Long-term oral etoposide in metastatic breast cancer: clinical and pharmacokinetic results. Cancer Treat Rev 19 suppl. C: 27–33, 1993Google Scholar
  21. 21.
    Atienza DM, Vogel CL, Trock B, Swain SM: Phase II study of oral VP-16-213 (etoposide) in patients with advanced breast cancer (Abstr). Breast Cancer Res Treat 27: 146, 1993Google Scholar
  22. 22.
    Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Clavel M, Seeber S, Conte P, Namer M, Bonneterre J, Fumoleau P, Sulkes A, Sauter Ch, Roche H, Calvert H, Kaufmann J, Chazard M, Diergarten K, Gallant G, Thompson M, Winograd B, Onetto N: Randomized trial of two doses of taxol in metastatic breast cancer: an interim analysis. Proc ASCO 12: 60, 1993Google Scholar
  23. 23.
    Verweij J, Clavel M, Chevallier B: Paclitaxel (TaxolTM) and Docetaxel (TaxotereTM): not simply two of a kind. Ann Oncol 5: 495–505, 1994Google Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • M. Bontenbal
    • 1
  • A. S. Th. Planting
    • 1
  • J. Verweij
    • 1
  • R. de Wit
    • 1
  • W. H. J. Kruit
    • 1
  • G. Stoter
    • 1
  • J. G. M. Klijn
    • 1
  1. 1.Department of Medical OncologyRotterdam Cancer InstituteRotterdamThe Netherlands

Personalised recommendations