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Cancer Chemotherapy and Pharmacology

, Volume 56, Issue 5, pp 487–491 | Cite as

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study

  • G. P. StathopoulosEmail author
  • D. Tsavdaridis
  • N. A. Malamos
  • S. K. Rigatos
  • Ch. Kosmas
  • N. Pergantas
  • J. G. Stathopoulos
  • J. Xynotroulas
Original Article

Abstract

Purpose: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. Methods: Forty-eight (median age 54 years, range 26–77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0–2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m2 for 90 min and docetaxel infusion 80 mg/m2 for 90 min, repeated once every 3 weeks. Results: Twenty-five (52.08%, 95% confidence interval [CI] 37.95–66.21) patients showed responses: 3 complete (6.25%, 95% CI 0–13.05) and 22 (45.83%, 95% CI 31.74–59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. Conclusion: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.

Keywords

Irinotecan Docetaxel Breast cancer 

References

  1. 1.
    Nabholtz JM, Falkson C, Campos D et al (2003) Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter phase III trial. J Clin Oncol 21:968–975PubMedGoogle Scholar
  2. 2.
    A’Hern R, Smith I, Ebbs S (1993) Chemotherapy and survival in advanced breast cancer: the infusion of doxorubicin in Cooper type regimens. Br J Cancer 67:807–813Google Scholar
  3. 3.
    Weber BL, Vogel C, Jones S et al (1995) Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. J Clin Oncol 13:2722–2730PubMedGoogle Scholar
  4. 4.
    Gianni L, Munzone E, Capri G et al (1995) Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer. J Clin Oncol 13:2688–2699PubMedGoogle Scholar
  5. 5.
    Dombernowsky P, Gehl J, Boesgaard M et al (1995) Treatment of metastatic breast cancer with paclitaxel and doxorubicin. Semin Oncol 22(Suppl 15):13–16Google Scholar
  6. 6.
    Seidman A, Reichman B, Crown J et al (1995) Paclitaxel as second and subsequent therapy for metastatic breast cancer: activity independent of prior anthracycline response. J Clin Oncol 13:1152–1159PubMedGoogle Scholar
  7. 7.
    Kornek G, Ulrich-Pur H, Penz M et al (2001) Treatment of advanced breast cancer with vinorelbine and docetaxel with or without human granulocyte colony-stimulating factor. J Clin Oncol 19:621–627PubMedGoogle Scholar
  8. 8.
    Greenberg PAC, Hortobagyi GN, Smith TL et al (1996) Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14:2197–2205PubMedGoogle Scholar
  9. 9.
    Falkson G, Tormey DC, Carey P et al (1991) Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer. Eur J Cancer 27:973–977PubMedGoogle Scholar
  10. 10.
    Crown J (1999) A review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer. Semin Oncol 26(Suppl):5–9PubMedGoogle Scholar
  11. 11.
    Trudeau ME, Eisenhauer EA, Higgins BP et al (1996) Docetaxel in patients with metastatic breast cancer: A phase II trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 14:422–428PubMedGoogle Scholar
  12. 12.
    Stathopoulos GP, Rigatos SK, Pergantas N et al (2002) Phase II Trial of biweekly administration of vinorelbine and gemcitabine in pretreated advanced breast cancer. J Clin Oncol 20:37–41PubMedGoogle Scholar
  13. 13.
    Dieras V, Chevallier B, Kerbrat P et al (1996) A multicentre phase II study of docetaxel 75 mg/m2 as first-line chemotherapy for patients with advanced breast cancer. Br J Cancer 74:650–656PubMedGoogle Scholar
  14. 14.
    Chevallier B, Fumoleau P, Kerbrat P et al (1996) Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: A phase II trial of the clinical screening co-operative group of the EORTC. Ann Oncol 7:165–171PubMedGoogle Scholar
  15. 15.
    Nabholtz JM, Senn HJ, Bezwoda WR et al (1999) Prospective randomized trial of docetaxel versus mitomycin C plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol 17:1413–1424PubMedGoogle Scholar
  16. 16.
    Paridaens R, Biganzoli L, Bruming P et al (2000) Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: A European Organisation for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol 18:724–733PubMedGoogle Scholar
  17. 17.
    Cunningham D, Pyrhonen S, James RD et al (1998) Randomized trial of irinotecan plus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352:1413–1418CrossRefPubMedGoogle Scholar
  18. 18.
    Rougier P, van Cutsem E, Bajetta E et al (1998) Randomized trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 352:1407–1412CrossRefPubMedGoogle Scholar
  19. 19.
    Sargent DJ, Niedzwiecki D, O’Connell MJ et al (2001) Recommendation for caution with irinotecan, fluorouracil and leucovorin for colorectal cancer. N Engl J Med 345:144–145CrossRefPubMedGoogle Scholar
  20. 20.
    Douillard J, Cunningham D, Roth A et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomized trial. Lancet 355:1041–1047CrossRefPubMedGoogle Scholar
  21. 21.
    Sjöström J, Blomqrist C, Mouridsen H et al (1999) Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: A randomized phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer 35:1194–1201PubMedGoogle Scholar
  22. 22.
    Chan S, Friedrichs K, Noel D et al (1999) Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 17:2341–2354PubMedGoogle Scholar
  23. 23.
    Nabholtz JM, Mackey JR, Smylie M et al (2001) Phase II study of docetaxel, doxorubicin and cyclophosphamide as a first-line chemotherapy for metastatic breast cancer. J Clin Oncol 19:314–321PubMedGoogle Scholar
  24. 24.
    Misset JL, Dieras V, Gruia G et al (1999) Dose-finding study of docetaxel and doxorubicin in first-line treatment of patients with metastatic breast cancer. Ann Oncol 10:553–560PubMedGoogle Scholar
  25. 25.
    Biganzoli L, Cufer T, Bruning P et al (2002) Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organisation for Research and Treatment of Cancer 10961 multicenter phase III trial. J Clin Oncol 20:3114–3121PubMedGoogle Scholar
  26. 26.
    Jassem J, Pienowski T, Plzanka A et al (2001) Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol 19:1707–1715PubMedGoogle Scholar
  27. 27.
    Rigatos SK, Stathopoulos GP, Pergantas N et al (2001) Docetaxel combined with irinotecan in pretreated advanced cancer patients phase I and II study, 11th international congress on anticancer treatment, vol 134, Paris (abstr S06)Google Scholar
  28. 28.
    Perez EA, Hillman DW, Mailliard JA et al (2004) Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline or taxane or both. J Clin Oncol 22:2849–2855PubMedGoogle Scholar
  29. 29.
    Sledge GW, Neuberg D, Bernardo P et al (2003) Phase III trial of doxorubicin, paclitaxel and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 21:588–592PubMedGoogle Scholar
  30. 30.
    Lucla HJ, Thomssen C, Untch M et al (2000) Multicenter phase III study in first line treatment of advanced metastatic breast cancer (ABC): epirubicin/paclitaxel (ET) vs epirubicin/cyclophosphamide (EC): a study of the AGO breast cancer group. Proc Am Soc Clin Oncol 19:73a (abstr 280)Google Scholar
  31. 31.
    Carmichael J (2001) UKCCR trial of epirubicin and cyclophosphamide (EC) vs epirubicin and Taxol (ET) in the first line treatment of women with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 20:22a. (abstr 84)Google Scholar
  32. 32.
    O’Shaughnessy J, Miles D, Vukelja S et al (2002) Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 20:2812–2823PubMedGoogle Scholar
  33. 33.
    Albain KS, Nag S, Calderillo-Ruiz G et al (2004) Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as a front-line therapy for metastatic breast cancer (MBC): first report of overall survival. Proc Am Soc Clin Oncol 22(15 suppl):14S (abstr 510)Google Scholar
  34. 34.
    Fountzilas G, Kalofonos HP, Dafni V et al (2004) Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic cooperative oncology group. Ann Oncol 15:1517–1526PubMedGoogle Scholar
  35. 35.
    Perez EA, Hillman DW, Stella PJ et al (2000) A Phase II study of paclitaxel plus carboplatin as first-line chemotherapy for women with metastatic breast carcinoma. Cancer 88:124–131PubMedGoogle Scholar
  36. 36.
    Mitchell PLR, Basser R, Chipman M et al (2004) A phase II study of escalated-dose docetaxel with granulocyte colony-stimulating factor support in patients with advanced breast cancer. Ann Oncol 15:585–589PubMedGoogle Scholar
  37. 37.
    Tabernero J, Climent MA, Lluch A et al (2004) A multicentre randomized phase II study of weekly or 3-weekly docetaxel in patients with metastatic breast cancer. Ann Oncol 15:1358–1365PubMedGoogle Scholar
  38. 38.
    Frasci G, Comello P, Thomas R et al (2004) Biweekly docetaxel-irinotecan with filgrastim support in pretreated breast and non-small-cell lung cancer patients. A phase I study. Cancer Chemother Pharmacol 53(1):25–32PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • G. P. Stathopoulos
    • 1
    Email author
  • D. Tsavdaridis
    • 2
  • N. A. Malamos
    • 3
  • S. K. Rigatos
    • 1
  • Ch. Kosmas
    • 4
  • N. Pergantas
    • 5
  • J. G. Stathopoulos
    • 1
  • J. Xynotroulas
    • 1
  1. 1.First Oncology DepartmentErrikos Dunant HospitalAthensGreece
  2. 2.Oncology UnitIKAThessalonikiGreece
  3. 3.Oncology UnitHelena HospitalAthensGreece
  4. 4.Metaxa HospitalPiraeusGreece
  5. 5.Oncology UnitIKAAthensGreece

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