Abstract
Background
To evaluate the feasibility and activity of gemcitabine and vinorelbine as a second/third-line approach in patients with advanced breast cancer.
Methods
Entered into the study were 51 consecutive patients. All had been previously treated with anthracyclines. Of these 51 patients, 36 had experienced failure or relapse after one chemotherapy line for advanced disease, and 15 after two chemotherapy lines. The dominant sites of involvement were brain in 4 patients (7.8%), liver in 22 (43.2%), lung in 10 (19.6%), bone in 10 (19.6), and soft-tissue in 5 (9.8%). Treatment consisted of vinorelbine 25 mg/m2 and gemcitabine 1000 mg/m2 administered on days 1 and 8 every 21 days.
Results
The scheme was well tolerated. Grade 3/4 neutropenia was observed in 11% of patients. Grade 3 nausea and vomiting occurred in 6%, and grade 2 neurotoxicity in 6%. No patients experienced grade 3/4 alopecia. The median relative dose intensity was 94.6% (49.7–100%) and 90.0% (23.1–100%) for vinorelbine and gemcitabine, respectively. Two patients (3.9%) were not evaluable for disease response, 4 (7.8%) attained a clinical complete response, 13 (25.5%) a partial response (for an overall response rate of 33.3%, 95% coefficient interval 20.0–46.0%), 23 (45.2%) showed stable disease, and 9 (17.6%) progressed. The median time to progression of responding patients was 10.8 months, and the median overall survival of the entire population was 17.8 months.
Conclusions
Vinorelbine and gemcitabine is a manageable scheme with moderate activity in pretreated patients with advanced breast cancer.
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References
Verdecchia A (1996) Survival in adult Italian cancer patients (1978–1989). ITACARE Working Group. Tumori 83:39–425
Hortobagyi GN (1994) Multidisciplinary management of advanced primary and metastatic breast cancer. Cancer 74 [1 Suppl 1]:416–423
Ellis MJ, Hayes DF, Lippman ME (2000) Treatment of metastatic breast cancer. In: Harris YR, Lippman ME, Morrow M, Osborne CK (eds) Diseases of the breast. Lippincott, Philadelphia, pp 749–787
Cardoso F, Di Leo A, Lohrisch C, Bernard C, Ferreira F, Piccart MJ (2002) Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades? Ann Oncol 13:197–207
Fellous A, Ohayon R, Vacassin T, Binet S, Lataste H, Krikorian A, Couzinier JP, Meininger V (1989) Biochemical effects of Navelbine on tubulin and associated proteins. Semin Oncol 16 [Suppl 4]:9–14
Johnson SA, Harper P, Hortobagyi GN, Pouillart P (1996) Vinorelbine: an overview. Cancer Treat Rev 22:127–142
Gasparini G, Caffo O, Barni S, Frontini L, Testolin A, Guglielmi RB, Ambrosini G (1994) Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol 12:2094–2101
Weber BL, Vogel C, Jones S, Harvey H, Hutchins L, Bigley J, Hohneker J (1995) Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. J Clin Oncol 13:1245–1252
Degardin M, Bonneterre J, Hecquet B, Pion JM, Adenis A, Horner D, Demaille A (1994) Vinorelbine (Navelbine) as salvage treatment for advanced breast cancer. Ann Oncol 5:423–426
Hertel LW, Kroin JS, Misner JW, Tustin JM (1988) Synthesis of 2-deoxy-2′,2′-difluoro-D-ribose and 2-deoxy-2′,2′'-difluoro-D-ribofuranosyl nucleosides. J Org Chem 53:2406–2409
Hertel LW, Boder GB, Kroin JS, Rinzel SM, Porre G, Todd GC, Grindey GB (1990) Evaluation of the antitumor activity of gemcitabine (2′,2′-difluoro-2′-deoxycitidine). Cancer Res 50:4417–4422
Luftner D, Flath B, Akrivakis C, Grunewald R, Mergenthaler HG, Possiger K (1998) Gemcitabine for palliative treatment in metastatic breast cancer. J Cancer Res Clin Oncol 124:527–531
Seidman AD (2001) The evolving role of gemcitabine in the management of breast cancer. Oncology 60:189–198
Lorusso V, Carpagnano F, Frasci G, Panza N, Di Rienzo G, Cisternino ML, Napoli G, Orlando S, Cinieri S, Brunetti C, Palazzo S, De Lena M (2000) Phase I/II study of gemcitabine plus vinorelbine as first-line chemotherapy of non-small-cell lung cancer. J Clin Oncol 18:405–411
Krajnik G, Mohn-Staudner A, Thaler J, Greil R, Schmeikal S, Marhold F, Deutsch J, Preiss P, Malayari R, Schafer-Prokop C, Wein W, Huber H, Pirker R (2000) Vinorelbine-gemcitabine in advanced non-small cell lung cancer (NSCLC): an AASLC phase II trial. Ann Oncol 11:993–998
Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C (1995) Paclitaxel by three-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
Dogliotti L, Berruti A, Buniva T, Zola P, Bau MG, Farris A, Sarobba MG, Bottini A, Alquati P, Deltetto F, Gosso P, Monzeglio C, Moro G, Sussio M, Perroni D (1996) Lonidamine significantly increases the activity of epirubicin in advanced breast cancer patients: results from a multicenter prospective randomized trial. J Clin Oncol 14:1165–1172
Haider K, Kornek GV, Kwasny W, Weinlander G, Valencak J, Lang F, Puribauer F, Kovats E, Depisch D, Scheithauer W (1999) Treatment of advanced breast cancer with gemcitabine and vinorelbine plus human granulocyte-colony stimulating factor. Breast Cancer Res Treat 55:203–211
Nicolaides C, Dimopoulos MA, Samantas E, Bafaloukos D, Kalofonos C, Fountzilas G, Razi E, Kosmidis P, Pavlidis N (2000) Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy: a phase II study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 11:873–875
Valenza R, Leonardi V, Gebbia V, Agostara B (2000) Gemcitabine and vinorelbine in pretreated advanced breast cancer. A pilot study. Ann Oncol 11:495–496
Hortobagyi G (2001) Treatment of advanced breast cancer with gemcitabine and vinorelbine. Oncology (Huntingt) 15 [Suppl 3]:15–17
Mariani G, Tagliabue P, Zucchinelli P, Brambilla C, Demicheli R, Villa E, Marchiaro A, Valagussa P, Bonadonna G, Gianni L (2001) Phase I/II study of gemcitabine in association with vinorelbine for metastatic breast cancer. Breast Cancer Res Treat 70:163–169
Stathopoulos GP, Rigatos SK, Pergantas N, Tsavdarides D, Athanasiadis I, Malamos NA, Stathopoulos JG (2002) Phase II trial of biweekly administration of vinorelbine and gemcitabine in pretreated advanced breast cancer. J Clin Oncol 20:37–41
Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10
Porkka K, Blomqvist C, Rissanen P, Elomea I, Pyrhonen S (1994) Salvage therapies in women who fail to respond to first-line treatment with fluorouracil, epirubicin and cyclophosphamide for advanced breast cancer. J Clin Oncol 12:1639–1647
Buzdar AU, Asmar L, Hortobagyi GN (1997) Impact of patient characteristics on treatment outcome: anthracycline resistance. Eur J Cancer 33 [Suppl 7]:S3–S6
Berruti A, Sperone P, Bottini A, Gorzegno G, Lorusso V, Brunelli A, Botta M, Tampellini M, Donadio M, Mancarella S, De Lena M, Alquati P, Dogliotti L (2000) Phase II study of vinorelbine with protracted fluorouracil infusion as a second- or third-line approach for advanced breast cancer patients previously treated with anthracyclines. J Clin Oncol 18:3370–3377
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This work is presented on behalf of the Piemonte Oncology Network.
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Donadio, M., Ardine, M., Berruti, A. et al. Gemcitabine and vinorelbine as second-line treatment in patients with metastatic breast cancer: a phase II study. Cancer Chemother Pharmacol 52, 147–152 (2003). https://doi.org/10.1007/s00280-003-0632-x
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DOI: https://doi.org/10.1007/s00280-003-0632-x