Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Nov;74(10):1668–1673. doi: 10.1038/bjc.1996.607

Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor.

G V Kornek 1, K Haider 1, W Kwasny 1, M Hejna 1, M Raderer 1, S Meghdadi 1, D Burger 1, B Schneeweiss 1, D Depisch 1, W Scheithauer 1
PMCID: PMC2074837  PMID: 8932353

Abstract

A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40-50 mg m(-2) diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m(-2) administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 microg kg(-1) day(-1) subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51%) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+ months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2-22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11%) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11%. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m(-2) VNB dose level), the tolerance of this regimen seems acceptable and justifies further evaluation in front-line and salvage therapy of advanced breast cancer.

Full text

PDF
1670

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson J. R., Bernstein L., Pike M. C. Approximate confidence intervals for probabilities of survival and quantiles in life-table analysis. Biometrics. 1982 Jun;38(2):407–416. [PubMed] [Google Scholar]
  2. Ayash L. J., Elias A., Wheeler C., Reich E., Schwartz G., Mazanet R., Tepler I., Warren D., Lynch C., Gonin R. Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study. J Clin Oncol. 1994 Jan;12(1):37–44. doi: 10.1200/JCO.1994.12.1.37. [DOI] [PubMed] [Google Scholar]
  3. Binet S., Chaineau E., Fellous A., Lataste H., Krikorian A., Couzinier J. P., Meininger V. Immunofluorescence study of the action of navelbine, vincristine and vinblastine on mitotic and axonal microtubules. Int J Cancer. 1990 Aug 15;46(2):262–266. doi: 10.1002/ijc.2910460220. [DOI] [PubMed] [Google Scholar]
  4. Canobbio L., Boccardo F., Pastorino G., Brema F., Martini C., Resasco M., Santi L. Phase-II study of Navelbine in advanced breast cancer. Semin Oncol. 1989 Apr;16(2 Suppl 4):33–36. [PubMed] [Google Scholar]
  5. Chevallier B., Fumoleau P., Kerbrat P., Dieras V., Roche H., Krakowski I., Azli N., Bayssas M., Lentz M. A., Van Glabbeke M. Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the Clinical Screening Cooperative Group of the European Organization for Research and Treatment of Cancer. J Clin Oncol. 1995 Feb;13(2):314–322. doi: 10.1200/JCO.1995.13.2.314. [DOI] [PubMed] [Google Scholar]
  6. Clavel M., Catimel G. Breast cancer: chemotherapy in the treatment of advanced disease. Eur J Cancer. 1993;29A(4):598–604. doi: 10.1016/s0959-8049(05)80161-3. [DOI] [PubMed] [Google Scholar]
  7. Degardin M., Bonneterre J., Hecquet B., Pion J. M., Adenis A., Horner D., Demaille A. Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. Ann Oncol. 1994 May;5(5):423–426. doi: 10.1093/oxfordjournals.annonc.a058873. [DOI] [PubMed] [Google Scholar]
  8. Fabi A., Tonachella R., Savarese A., Cirulli S., Tomao S., Conte E., Cognetti F. A phase II trial of vinorelbine and thiotepa in metastatic breast cancer. Ann Oncol. 1995 Feb;6(2):187–189. doi: 10.1093/oxfordjournals.annonc.a059115. [DOI] [PubMed] [Google Scholar]
  9. Falkson G., Gelman R., Falkson C. I., Glick J., Harris J. Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study. J Clin Oncol. 1991 Dec;9(12):2153–2161. doi: 10.1200/JCO.1991.9.12.2153. [DOI] [PubMed] [Google Scholar]
  10. Fumoleau P., Delgado F. M., Delozier T., Monnier A., Gil Delgado M. A., Kerbrat P., Garcia-Giralt E., Keiling R., Namer M., Closon M. T. Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol. 1993 Jul;11(7):1245–1252. doi: 10.1200/JCO.1993.11.7.1245. [DOI] [PubMed] [Google Scholar]
  11. Gasparini G., Caffo O., Barni S., Frontini L., Testolin A., Guglielmi R. B., Ambrosini G. Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol. 1994 Oct;12(10):2094–2101. doi: 10.1200/JCO.1994.12.10.2094. [DOI] [PubMed] [Google Scholar]
  12. Hohneker J. A. A summary of vinorelbine (Navelbine) safety data from North American clinical trials. Semin Oncol. 1994 Oct;21(5 Suppl 10):42–47. [PubMed] [Google Scholar]
  13. Holmes F. A., Walters R. S., Theriault R. L., Forman A. D., Newton L. K., Raber M. N., Buzdar A. U., Frye D. K., Hortobagyi G. N. Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst. 1991 Dec 18;83(24):1797–1805. doi: 10.1093/jnci/83.24.1797-a. [DOI] [PubMed] [Google Scholar]
  14. Kornek G., Raderer M., Depisch D., Haider K., Fazeny B., Dittrich C., Scheithauer W. Amonafide as first-line chemotherapy for metastatic breast cancer. Eur J Cancer. 1994;30A(3):398–400. doi: 10.1016/0959-8049(94)90264-x. [DOI] [PubMed] [Google Scholar]
  15. Luedke D., McLaughlin T. T., Daughaday C., Luedke S., Harrison B., Reed G., Martello O. Mitomycin C and vindesine associated pulmonary toxicity with variable clinical expression. Cancer. 1985 Feb 1;55(3):542–545. doi: 10.1002/1097-0142(19850201)55:3<542::aid-cncr2820550312>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  16. Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  17. Pouillart R., Huong T. H., Brugerie E., Lheritier J. Sequential administration of two oncostatic drugs: study of modalities for pharmacodynamic potentiation. Biomedicine. 1974 Dec 10;21(12):471–479. [PubMed] [Google Scholar]
  18. Reichman B. S., Seidman A. D., Crown J. P., Heelan R., Hakes T. B., Lebwohl D. E., Gilewski T. A., Surbone A., Currie V., Hudis C. A. Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol. 1993 Oct;11(10):1943–1951. doi: 10.1200/JCO.1993.11.10.1943. [DOI] [PubMed] [Google Scholar]
  19. Romero A., Rabinovich M. G., Vallejo C. T., Perez J. E., Rodriguez R., Cuevas M. A., Machiavelli M., Lacava J. A., Langhi M., Romero Acuña L. Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. J Clin Oncol. 1994 Feb;12(2):336–341. doi: 10.1200/JCO.1994.12.2.336. [DOI] [PubMed] [Google Scholar]
  20. Rowinsky E. K., Cazenave L. A., Donehower R. C. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst. 1990 Aug 1;82(15):1247–1259. doi: 10.1093/jnci/82.15.1247. [DOI] [PubMed] [Google Scholar]
  21. Scheithauer W., Dittrich C., Kornek G., Haider K., Linkesch W., Gisslinger H., Depisch D. Phase II study of amonafide in advanced breast cancer. Breast Cancer Res Treat. 1991 Dec;20(1):63–67. doi: 10.1007/BF01833358. [DOI] [PubMed] [Google Scholar]
  22. Scheithauer W., Kornek G., Haider K., Kwasny W., Schenk T., Pirker R., Depisch D. Effective second line chemotherapy of advanced breast cancer with navelbine and mitomycin C. Breast Cancer Res Treat. 1993;26(1):49–53. doi: 10.1007/BF00682699. [DOI] [PubMed] [Google Scholar]
  23. Spielmann M., Dorval T., Turpin F., Antoine E., Jouve M., Maylevin F., Lacombe D., Rouesse J., Pouillart P., Tursz T. Phase II trial of vinorelbine/doxorubicin as first-line therapy of advanced breast cancer. J Clin Oncol. 1994 Sep;12(9):1764–1770. doi: 10.1200/JCO.1994.12.9.1764. [DOI] [PubMed] [Google Scholar]
  24. Sørensen J. B. Current position of vinorelbine in cancer chemotherapy. Ann Oncol. 1995 Feb;6(2):105–107. doi: 10.1093/oxfordjournals.annonc.a059101. [DOI] [PubMed] [Google Scholar]
  25. Toussaint C., Izzo J., Spielmann M., Merle S., May-Levin F., Armand J. P., Lacombe D., Tursz T., Sunderland M., Chabot G. G. Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer. J Clin Oncol. 1994 Oct;12(10):2102–2112. doi: 10.1200/JCO.1994.12.10.2102. [DOI] [PubMed] [Google Scholar]
  26. Valagussa P., Bonadonna G., Veronesi U. Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients. Cancer. 1978 Mar;41(3):1170–1178. doi: 10.1002/1097-0142(197803)41:3<1170::aid-cncr2820410355>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES