Regular Article

British Journal of Cancer (2000) 83, 438–442. doi:10.1054/bjoc.2000.1306 www.bjcancer.com
Published online 25 July 2000

A phase II trial of paclitaxel and epirubicin in advanced breast cancer

D Rischin1, J Smith2, M Millward1, C Lewis3, M Boyer4, G Richardson5, G Toner1, H Gurney6 and J McKendrick7

  1. 1Division of Haematology and Medical Oncology, Melbourne, Australia
  2. 2Statistical Centre, Peter MacCallum Cancer Institute, Melbourne, Australia
  3. 3Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia
  4. 4Department of Medical Oncology, Royal Prince Alfred Hospital, Sydney, Australia
  5. 5Department of Medical Oncology, Monash Medical Centre, Melbourne, Australia
  6. 6Department of Medical Oncology, Westmead Hospital, Sydney, Australia
  7. 7Department of Medical Oncology, Box Hill Hospital, Melbourne, Australia

Received 17 November 1999; Revised 28 February 2000; Accepted 13 April 2000.

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Abstract

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0–2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m–2followed by a 3-h infusion of paclitaxel 175 mg m–2repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38–69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4–10.0) and estimated median overall survival was 17.9 months (95% CI 14.2–25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of greater than or equal to20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m–2and epirubicin 75 mg m–2is a well tolerated, promising regimen for the treatment of advanced breast cancer. © 2000 Cancer Research Campaign

Keywords:

taxanes, anthracyclines, breast cancer, phase II

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References

  1. Berg SL, Cowan KH, Bolis FM, Fisherman JS, Denicoff AM, Hillig M, Poplack DG and O'Shaughnessy JA (1994) Pharmacokinetics of taxol and doxorubicin administered alone and in combination by continuous 72 hour infusion. J Natl Cancer Inst 86: 143–145
  2. Bonadonna G, Gianni L, Santoro A, Bonfante V, Bidoli P, Casali P, Demicheli R and Valagussa P (1993) Drugs ten years later: Epirubicin. Ann Oncol 4: 359–369
  3. Carmichael J, Jones A and Hutchinson T (1997) A phase II trial of epirubicin plus paclitaxel in metastatic breast cancer. Semin Oncol 24: S17-44–S17–47
  4. Catimel G, Spielmann M, Dieras V, Tubiana-hulin M, Bonneterre J, Pouillart P, Kayitalire L, Guastalla JP, Graffand Ni, Garet F, Dumortier A and Pellae-Cosset B (1997) Phase I studies of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide in patients with metastatic breast cancer: the French experience. Semin Oncol 24: S8–12 | PubMed |
  5. Conte PF, Baldini E, Gennari A, Michelotti A, Salvadori B, Tibaldi C, Danesi R, Innocenti F, Gentile A, Dell'Anna R, Biadi O, Mariani M and Del Tacca M (1997) 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 15: 2510–2517 | PubMed | ISI | ChemPort |
  6. Conte PF and Gennari A (1997) Anthracyclines-paclitaxel combinations in the treatment of breast cancer. Ann Oncology 8: 939–943
  7. Gehl J, Boesgard M, Paaske T, Jensen V and Dombernowsky P (1996) Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Ann Oncol 7: 687–693 | PubMed | ISI | ChemPort |
  8. Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C, Stefanelli M, Valagussa P and Bonadonna G (1995) Paclitaxel by 3 hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumour efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol 13: 2688–2699 | PubMed | ISI | ChemPort |
  9. Gianni L, Vigano L, Locatelli A, Capri G, Giani A, Tarenzi E and Bonadonna G (1997 a) Human pharmacokinetic characterisation and in-vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. J Clin Oncol 15: 1906–1915 | PubMed | ISI | ChemPort |
  10. Gianni L, Bigano L, Locatelli A, Giani A, Capri G, Bertuzzi A, Grasselli G, Tarenzi E and Bonadonna G (1997 b) Different interference of paclitaxel (PTX) on human pharmacokinetics of doxorubicin (DOX) and epirubicin (EPI). Proc Am Soc Clin Oncol 16: 786
  11. Holmes FA, Madden T, Newman RA, Valero V, Theriault RL, Fraschini G, Walters RS, Booser DJ, Buzdar AU, Willey J and Hortobagyi GN (1996) Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer. J Clin Oncol 14: 2713–2721 | PubMed | ISI | ChemPort |
  12. Hortobagyi G and Holmes FA (1997) Optimal dosing of paclitaxel and doxorubicin in metastatic breast cancer. Semin Oncol 24: S3–4–S3–7
  13. Luck HJ, Thomssen C, du Bois A, Untch M, Lisboa BW, Kohler B and Diegarten K (1997) Metastatic breast cancer: experience with the combination epirubicin plus paclitaxel. Oncology (Huntingt) 12: 36–39
  14. Millward MJ, Webster LK, Rischin D, Stokes KH, Toner GC, Bishop JF, Olver IN, Linahan BM, Linsenmeyer ME and Woodcock DM (1998) Phase I trial of Cremophor EL with bolus doxorubicin. Clin Cancer Res 4: 2321–2329
  15. Nabholtz JM, Falkson G, Campos D, Szanto J, Martin M, Chan S, Pienkowski T, Bezwoda WR, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A and Pouillart P (1999). Proc Am Soc Clin Oncol 18: 85
  16. Rischin D, Webster L, Millward M, Toner G, Nawaratne S, Ganju V, Francis P and Bishop J (1999) A phase I and pharmacokinetic study of paclitaxel and epirubicin in advanced cancer. Inv New Drugs 17: 73–80
  17. Sledge GW Jr, Neuberg D, Ingle J, Martino S and Wood W (1997) Phase III trial of doxorubicin (A) vs paclitaxel (T) vs doxorubicin + paclitaxel (A + T) as first-line therapy for metastatic breast cancer (MBC): an intergroup trial. Proc Am Soc Clin Oncol 16: 2
  18. S-plus 4.0.3. (1997). MathSoft Inc: Seattle, WA
  19. StatXact 4.0.1. (1999). Cytel Software Corporation: Cambridge, MA