Skip to main content
SpringerLink
Log in

Cisplatin–epirubicin–paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology group (SICOG) phase II study

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose.It has been shown in vitro that both cisplatin and epirubicin increase the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at defining the antitumor activity of a weekly cisplatin–epirubicin–paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients.

Patients and methods.Sixty-eight breast cancer patients with advanced disease, who had not received prior chemotherapy (except adjuvant), received weekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm plus G-CSF (day 3–5), for a maximum of 12 cycles. Thirty-five patients had stage IIIB and 33 stage IV disease (14 with visceral metastases).

Results.All patients were evaluable for response on an intent to treat basis. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76–94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81–99%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI–61–91%). Surgery was performed in 33/35 women with locally advanced disease. Four of these patients (11%) showed no invasive cancer on pathologic examination, and in an additional 8 patients tumor < 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3–19), 11 patients had progressed and 5 had died among the 33 patients with metastatic disease, the median progression-free survival in this group being 14 months. Severe hematologic toxicity was uncommon, grade 3–4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registered. Packed red blood cell transfusions were required in 7 patients. Vomiting, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients.

Conclusions.The weekly PET administration is a well tolerated and very effective approach in advanced breast cancer patients. It can produce a 40% clinical complete response rate, with a more than 10% pCR rate in patients with T4 disease, and an about 80% ORR in those with distant metastases. A phase III trial comparing PET with a standard every 3 weeks epirubicin—taxol administration is underway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Early Breast Cancer Trialists Collaborative Group: Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet 352: 930–942, 1998

    Google Scholar 

  2. Fossati R, Confalonieri C, Torri V, Ghislandi B, Penna A, Pistotti V, Tinazzi A, Liberati A: Cytotoxic and hormonal treatment for metastatic breast cancer. A systematic review of published randomized trials involving 31,510 women. J Clin Oncol 16: 3439–3460, 1998

    PubMed  Google Scholar 

  3. Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU: Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14: 2197–2205, 1996

    PubMed  Google Scholar 

  4. Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Budzar AU, Frye DK, Hortobagyi GN: Phase II trial of Taxol: An active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83: 1797–1805, 1991

    PubMed  Google Scholar 

  5. Seidman AD, Reichman BS, Crown JP, Yao TJ, Currie V, Hakes TB, Hudis CA, Gilewski TA, Baselga J, Forsythe P, Lepore J, Marks L, Fain K, Souhrada M, Onetto N, Arbuck S, Norton L: Paclitaxel as second and subsequent therapy for metastatic breast cancer: Activity independent of prior anthracycline response. J Clin Oncol 13: 1152–1159, 1995

    PubMed  Google Scholar 

  6. Chevallier B, Fumoleau P, Kerbrat P, Azli N, BayssasM, Lentz MA, van Glabbeke M, Dieras V, Roche H, Krakowski I: 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 13: 314–324, 1995

    PubMed  Google Scholar 

  7. Seidman AD, Hudis CA, Albanel J, Tong W, Tepler I, Currie V, Moynahan M, Theodoulou M, Gollub M, Baselga J, Norton L: Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 16: 3353–3361, 1998

    PubMed  Google Scholar 

  8. Sikov W, Akerley W, Strenger R, Cummings F: Weekly highdose paclitaxel demonstrates significant activity in advanced breast cancer (abstract). Proc Am Soc Clin Oncol 17: 112a, 1998

    Google Scholar 

  9. Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laifranchi A, Caraceni, A, Martini C, Stefanelli M, Valagussa P, Bonadonna G: 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 13: 2688–2699, 1995

    PubMed  Google Scholar 

  10. Frassineti GL, Zoli W, Tienghi A, Ravaioli A, Milandri C, Gentile A, Onetto N, Arnadori D: Phase II study of sequential combination of paclitaxel and doxorubicin in the treatment of advanced breast cancer (abstract). Proc Am Soc Clin Oncol 15: 109, 1996

    Google Scholar 

  11. Schwartsmann G, Menke CH, Caleffi M, Xavier N, Ferreira Filho AF, Schunemann H, Koya R, Stroda PR, Pohlmann P, Vengas LF, Kalakun L: Phase II trial of taxol, doxorubicin plus G-CSF in patients with metastatic breast cancer (abstract). Proc Am Soc Clin Oncol 15: 126, 1996

    Google Scholar 

  12. Conte PF, Baldini E, Gennari A, Salvadori B, Gennari A, Da Prato M, Tibaldi C, Salzano E, Gentile A: Dose-finding study and pharrnacokinetics 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, 1997

    PubMed  Google Scholar 

  13. Sledge CW, Neuberg D, Ingle J, Martino S, Wood W: 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 (abstract). Proc Am Soc Clin Oncol 16: la, 1997

    Google Scholar 

  14. Sledge GW, Loehrer PJ, Roth BJ, Einhom LH: Cisplatin as first-line therapy for metastatic breast cancer. J Clin Oncol 6: 1811–1814, 1988

    PubMed  Google Scholar 

  15. Smith IE, Talbot DC: Cisplatin and its analogues in the treatment of advanced breast cancer. A review: Br J Cancer 65: 787–793, 1992

    Google Scholar 

  16. Dogliotti L, Danese S, Berruti A, Zola P, Bottini A, Buniva T, Richiardi G, Moro G, Farrris A, Porcile G, Zaffaroni N: Epirubicin, cisplatin and lonidamine in advanced breast cancer. A phase II study (abstract). Proc Am Soc Clin Oncol 15: 140, 1996

    Google Scholar 

  17. Roy SN, Horwitz SB: A phosphoglycoprotein associated with with taxol-resistance in J774.2 cells. Cancer Res 45: 3856–3863, 1985

    PubMed  Google Scholar 

  18. Parker RJ, Eastman A, Bostick-Bruton F, Reed E: Acquired cisplatin resistance in human ovarian cancer cells is associated with enhanced repair of cisplatin–DNA lesions and reduced drug accumulation. J Clin Invest 87: 772–777, 1991

    PubMed  Google Scholar 

  19. Frasci G, Comella P, D'Aiuto G, Budillon A, Barbarulo D, Thomas R, Capasso L, Casaretti R, Daponte A, Caponigro F, Gravina A, Carteni' G, Gentile A, Comella G. Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study. Breast Cancer Res. Treat 49: 13–26, 1998

    PubMed  Google Scholar 

  20. Gelmon KA, O'Reilly SE, Tolcher AW, Zola P, Bottini A, Buniva T, Richiardi G, Moro G, Farms A, Porcile G, Zaffaroni N: Phase I/II study of biweekly paclitaxel and cisplatin in the treatment of metastatic breast cancer. J Clin Oncol 14: 1185–1191, 1996

    PubMed  Google Scholar 

  21. McCaskill-Stevens W, Ansari R, Fisher W, Pennington K, Dobbs C, Gonin R, Schaefer S, Loesch D, Sledge G: Phase II study of biweekly cisplatin and paclitaxel in the treatment of metastatic breast cancer (abstract). Proc Am Soc Clin Oncol 15: 120, 1996

    Google Scholar 

  22. Sparano JA, Neuberg D, Glick JH, Robert NJ, Goldstem U, Sledge GW, Wood W: A phase II trial of biweekly paclitaxel and cisplatin in patients with advanced breast carcinoma: an Eastern Cooperative Oncology Group trial. (abstract) Proc Am Soc Clin Oncol 15: 114, 1996

    Google Scholar 

  23. Frasci G, D'Aiuto G, Comella P, Apicella A, Thomas R, Capasso L, Di Bonito M, Carteni G, Biglietto M, De Lucia L, Maiorino L, Piccolo S, Bianchi U, D' Aniello R, Lapenta L, Comella G: Cisplatin–epirubicin–paclitaxel weekly administration in advanced breast cancer: A phase I study of the Southern Italy Cooperative Oncology Group. Breast Cancer Res Treat 56: 239–252, 1999

    PubMed  Google Scholar 

  24. Miller AB, HQogstratep B, Staquet M: Reporting results of cancer treatment. Cancer 47: 207–214, 1981

    PubMed  Google Scholar 

  25. Kaplan ES, and Meier P: Non parametric estimation for incomplete observations. J Am Stat Assoc 53: 557–580, 1958

    Google Scholar 

  26. Simon R, Wittes RE, Ellenberg SS: Randomised phase II clinical trials, Cancer Treat Rep 69: 1375–1381, 1985

    PubMed  Google Scholar 

  27. Sola C, Lluch A, Garcia-Conde I, Ojeda B, Hornedo J, Benavides M, Solano C, Garcia T, Salazar R, Alonso S, Cortes-Funes H, Lopez JJ: Phase II study of weekly paclitaxel in recurrent breast cancer after high-dose chemotherapy (abstract). Proc Am Soc Clin Oncol 17: 174a, 1998

    Google Scholar 

  28. Alvarez A, Mickiewicz E, Brosio C, Giglio R, Cinat G, Suarez A: Weekly taxol in patients who had relapsed or remained stable with taxol in a 21 day schedule (abstract). Proc Am Soc Clin Oncol 17: 188a, 1998

    Google Scholar 

  29. Perez EA, Irwin DR, Patel R. et al.: A large phase II trial of paclitaxel administered as a weekly 1-hour infusion in patients with metastatic breast cancer. Proc Am Soc Clin Oncol 18: 126a, 1999

    Google Scholar 

  30. Kohler U, Olbricht SS, Fuechsel G, Keffner E, Richter B, Ridwelski K: Weekly paclitaxel with epirubicin as second-line therapy of metastatic breast cancer. Results of a clinical phase II study. Semin Oncol 24 (17) 40–43, 1997.

    Google Scholar 

  31. van der Burgh MEL, de Wit R, Stoter G, Verweij J: Phase I study of weekly cisplatin and weekly or 4-weekly taxol: a highly active regimen in advanced epithelial ovarian cancer (abstract) Proc Am Soc Clin Oncol 17: 355a, 1998

    Google Scholar 

  32. Bianco AR, DeLaurentis M, Carlomagno C. et al.: 20 year update of the Naples GUN trial of adjuvant breast cancer therapy: evidence of interaction between c-erbB2 expression and tamoxifen efficacy. Proc Am Soc Clin Oncol 17: 97a, 1998

    Google Scholar 

  33. Untch M, Konecny G, Lebeau A., et al.: Dose-intensification of anthracycline in the adjuvant treatment of high-risk breast cancer and c-erbB2 overexpression. Proc Am Soc Clin Oncol 17: 102a, 1998

    Google Scholar 

  34. Colomer R, Montere S, Lluch A, et al.: Circulating HER2/Neu predicts resistance to taxol/adriamycin in metastatic breast carcinoma: preliminary results of a multicentric prospective study. Proc Am Soc Clin Oncol 16: 140a, 1997

    Google Scholar 

  35. Norton L, Slamon D, Leyland-Jones B, Wolter J, Fleming T, Eirmann W, Baselga J, Mendelsohn J, Bajamonde A, Ash M, Shak S: Overall survival advantage to simultaneous chemotherapy plus humanized anti-HER 2 monoclonal antibody herceptin in HER2-overexpressing metastatic breast cancer. Proc Am Soc Clin Oncol 18: 127a, 1999

    Google Scholar 

  36. Fornier M, Seidman AD, Esteva FJ, Theodoulou M, Moynahan M, Currie V, Moasser M, Sklarin N, Gilewski T, Surbone A, Denton C, Bacoffi D, Willey J, Bach A, Reuter V, Hortobagyi G, Norton L, Hudis C: Weekly herceptin + 1-hr taxol: phase II study in HER2 overexpressing and nonoverexpressing metastatic breast cancer. Proc Am Soc Clin Oncol 18: 126a, 1999

    Google Scholar 

  37. Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, Cruz AB, Fisher ER, Wickerman DL, Wolmark N, DeCillis A, Hoehn JL, Lees AW, Dimitrov NY: Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15: 2483–2494, 1997

    PubMed  Google Scholar 

  38. Moliterni A, Tarenzi E, Capri G, Terenziani M, Bertuzzi A, Grasselli G, Agresti R, Piotti P, Greco M, Salvadori B, Pilotti S, Lombardi F, Valagussa P, Bonadonna G, Gianni L: Pilot study of primary chemotherapy with doxorubicin plus paclitaxel in women with locally advanced or operable breast cancer. Semin Oncol 24(17) 10–14, 1997

    Google Scholar 

  39. Henderson IC, Berry G, Demetri C, Cirrincione C, Goldstein L, Martino S, Ingle JN, Cooper MR, Canellos G, Burderi F, Fleming G, Holland M, Graziano S, Carpenter J, Muss H, Norton L: Improved disease-free and overall survival from the addition of sequential paclitaxel but not from the escalation of doxorubicin dose level in the adjuvant chemotherapy of patients with node-positive primary breast cancer. Proc Am Soc Clin Oncol 17: l0la, 1998

    Google Scholar 

  40. Hudis C, Seidman A, Baselga J, Raptis J, Lebwohl D, Gilewski T, Moynahan M, Skarin N, Fennelly D, Crown PA, Surbone, A, Uhlenhopp M, Riedel F, Yao U, and Norton L: Sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide for resectable high-risk breast cancer: feasibility and efficacy. J Clin Oncol 17: 93–100, 1999

    PubMed  Google Scholar 

Download references

Authors
  1. Giuseppe Frasci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe D'Aiuto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pasquale Comella
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Renato Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Immacolata Capasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maurizio Di Bonito
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Flavia Rivellini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giacomo Carteni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Luigi De Lucia
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luigi Maiorino
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Roberta D'Aniello
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pasquale Frezza
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Liliana Lapenta
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Giuseppe Comella
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frasci, G., D'Aiuto, G., Comella, P. et al. Cisplatin–epirubicin–paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology group (SICOG) phase II study. Breast Cancer Res Treat 62, 87–97 (2000). https://doi.org/10.1023/A:1006429205363

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006429205363

Search

Navigation