Abstract
Anthracyclines and taxanes are very effective drugs in the treatment of advanced breast cancer. With G-CSF support, the dose-intensity of this combination can be increased by reducing the interval between chemotherapy cycles, the so-called ‘shortening of cycle time’. We treated 36 patients with advanced breast cancer in a multicentre phase I/II study. The treatment regimen consisted of epirubicin 75 mg m−2followed by paclitaxel 135 mg m−2(3 h) in combination with G-CSF. At least six patients were treated in each cohort and were evaluated over the first three cycles. Starting at an interval of 14 days, in subsequent cohorts of patients the interval could be shortened to 10 days. An 8-day interval was not feasible due mainly to incomplete neutrophil recovery at the day of the next scheduled cycle. In the 10-day interval cohort it was feasible to increase the paclitaxel dose to 175 mg m−2. The haematological and non-haematological toxicity was relatively mild. No cumulative myelosuppression was observed over at least three consecutive cycles. In combination with G-CSF, epirubicin 75 mg m−2and paclitaxel 175 mg m−2could be safely administered every 10 days over at least three cycles, enabling a dose intensity of 52 and 122 mg m−2per week, respectively. © 2000 Cancer Research Campaign
Keywords: combination chemotherapy, breast neoplasms, dose-intensive, epirubicin, paclitaxel
Full Text
The Full Text of this article is available as a PDF (73.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brambilla C., Rossi A., Bonfante V., Ferrari L., Villani F., Crippa F., Bonadonna G. Phase II study of doxorubicin versus epirubicin in advanced breast cancer. Cancer Treat Rep. 1986 Feb;70(2):261–266. [PubMed] [Google Scholar]
- Catimel G., Spielmann M., Dieras V., Kayitalire L., Pouillart P., Guastalla J. P., Soler-Michel P., Graffand N., Garet F., Dumortier A. Phase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety. Semin Oncol. 1996 Feb;23(1 Suppl 1):24–27. [PubMed] [Google Scholar]
- Conte P. F., Baldini E., Gennari A., Michelotti A., Salvadori B., Tibaldi C., Danesi R., Innocenti F., Gentile A., Dell'Anna R. Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer. J Clin Oncol. 1997 Jul;15(7):2510–2517. doi: 10.1200/JCO.1997.15.7.2510. [DOI] [PubMed] [Google Scholar]
- Conte P. F., Michelotti A., Baldini E., Salvadori B., Gennari A., Da Prato M., Tibaldi C., Salzano E., Gentile A. A dose-finding study of epirubicin in combination with paclitaxel in the treatment of advanced breast cancer. Semin Oncol. 1996 Oct;23(5 Suppl 11):28–31. [PubMed] [Google Scholar]
- Eisenhauer E. A., ten Bokkel Huinink W. W., Swenerton K. D., Gianni L., Myles J., van der Burg M. E., Kerr I., Vermorken J. B., Buser K., Colombo N. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994 Dec;12(12):2654–2666. doi: 10.1200/JCO.1994.12.12.2654. [DOI] [PubMed] [Google Scholar]
- Fisherman J. S., McCabe M., Noone M., Ognibene F. P., Goldspiel B., Venzon D. J., Cowan K. H., O'Shaughnessy J. A. Phase I study of Taxol, doxorubicin, plus granulocyte-colony stimulating factor in patients with metastatic breast cancer. J Natl Cancer Inst Monogr. 1993;(15):189–194. [PubMed] [Google Scholar]
- Gehl J., Boesgaard M., Paaske T., Vittrup Jensen B., Dombernowsky P. Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Ann Oncol. 1996 Sep;7(7):687–693. doi: 10.1093/oxfordjournals.annonc.a010717. [DOI] [PubMed] [Google Scholar]
- Gennari A., Salvadori B., Donati S., Bengala C., Orlandini C., Danesi R., Del Tacca M., Bruzzi P., Conte P. F. Cardiotoxicity of epirubicin/paclitaxel-containing regimens: role of cardiac risk factors. J Clin Oncol. 1999 Nov;17(11):3596–3602. doi: 10.1200/JCO.1999.17.11.3596. [DOI] [PubMed] [Google Scholar]
- Gianni L., Munzone E., Capri G., Fulfaro F., Tarenzi E., Villani F., Spreafico C., Laffranchi A., Caraceni A., Martini C. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995 Nov;13(11):2688–2699. doi: 10.1200/JCO.1995.13.11.2688. [DOI] [PubMed] [Google Scholar]
- Gianni L., Munzone E., Capri G., Villani F., Spreafico C., Tarenzi E., Fulfaro F., Caraceni A., Martini C., Laffranchi A. Paclitaxel in metastatic breast cancer: a trial of two doses by a 3-hour infusion in patients with disease recurrence after prior therapy with anthracyclines. J Natl Cancer Inst. 1995 Aug 2;87(15):1169–1175. doi: 10.1093/jnci/87.15.1169. [DOI] [PubMed] [Google Scholar]
- Gianni L. Theoretical and practical aspects of paclitaxel scheduling. Ann Oncol. 1995 Nov;6(9):861–863. doi: 10.1093/oxfordjournals.annonc.a059349. [DOI] [PubMed] [Google Scholar]
- Henderson I. C., Hayes D. F., Gelman R. Dose-response in the treatment of breast cancer: a critical review. J Clin Oncol. 1988 Sep;6(9):1501–1515. doi: 10.1200/JCO.1988.6.9.1501. [DOI] [PubMed] [Google Scholar]
- Jain K. K., Casper E. S., Geller N. L., Hakes T. B., Kaufman R. J., Currie V., Schwartz W., Cassidy C., Petroni G. R., Young C. W. A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J Clin Oncol. 1985 Jun;3(6):818–826. doi: 10.1200/JCO.1985.3.6.818. [DOI] [PubMed] [Google Scholar]
- Kobrinsky N. L., Sjolander D. E., Cheang M. S., Levitt R., Steen P. D. Granulocyte-macrophage colony-stimulating factor treatment before doxorubicin and cyclophosphamide chemotherapy priming in women with early-stage breast cancer. J Clin Oncol. 1999 Nov;17(11):3426–3430. doi: 10.1200/JCO.1999.17.11.3426. [DOI] [PubMed] [Google Scholar]
- Lalisang R. I., Wils J. A., Nortier H. W., Burghouts J. T., Hupperets P. S., Erdkamp F. L., Schouten H. C., Blijham G. H. Comparative study of dose escalation versus interval reduction to obtain dose-intensification of epirubicin and cyclophosphamide with granulocyte colony-stimulating factor in advanced breast cancer. J Clin Oncol. 1997 Apr;15(4):1367–1376. doi: 10.1200/JCO.1997.15.4.1367. [DOI] [PubMed] [Google Scholar]
- 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]
- Nabholtz J. M., Gelmon K., Bontenbal M., Spielmann M., Catimel G., Conte P., Klaassen U., Namer M., Bonneterre J., Fumoleau P. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 1996 Jun;14(6):1858–1867. doi: 10.1200/JCO.1996.14.6.1858. [DOI] [PubMed] [Google Scholar]
- Sledge G. W., Jr, Robert N., Sparano J. A., Cobeligh M., Goldstein L. J., Neuberg D., Rowinsky E., Baughman C., McCaskill-Stevens W. Paclitaxel (Taxol)/doxorubicin combinations in advanced breast cancer: the Eastern Cooperative Oncology Group experience. Semin Oncol. 1994 Oct;21(5 Suppl 8):15–18. [PubMed] [Google Scholar]
- Tjan-Heijnen V. C., Biesma B., Festen J., Splinter T. A., Cox A., Wagener D. J., Postmus P. E. Enhanced myelotoxicity due to granulocyte colony-stimulating factor administration until 48 hours before the next chemotherapy course in patients with small-cell lung carcinoma. J Clin Oncol. 1998 Aug;16(8):2708–2714. doi: 10.1200/JCO.1998.16.8.2708. [DOI] [PubMed] [Google Scholar]
- Vadhan-Raj S., Broxmeyer H. E., Hittelman W. N., Papadopoulos N. E., Chawla S. P., Fenoglio C., Cooper S., Buescher E. S., Frenck R. W., Jr, Holian A. Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level. J Clin Oncol. 1992 Aug;10(8):1266–1277. doi: 10.1200/JCO.1992.10.8.1266. [DOI] [PubMed] [Google Scholar]
- de Wit R., Verweij J., Bontenbal M., Kruit W. H., Seynaeve C., Schmitz P. I., Stoter G. Adverse effect on bone marrow protection of prechemotherapy granulocyte colony-stimulating factor support. J Natl Cancer Inst. 1996 Oct 2;88(19):1393–1398. doi: 10.1093/jnci/88.19.1393. [DOI] [PubMed] [Google Scholar]
