Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer
We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated, breast cancer patients as salvage chemotherapy.
A weekly infusion of gemcitabine at 850 mg/m2for 30 min, for 3 of every 4 weeks, was introduced in advanced breast cancer patients who had failed previous doxorubicin and taxane based chemotherapy. There was no dose modification, and the treatment was delayed until the leukopenia was recovered with G-CSF support. The efficacy was evaluated every three cycles and the treatment was continued until either disease progression or 12 cycles.
Of 41 enrolled patients, 38 were evaluable with a median age of 47. Total 178 cycles of gemcitabine was administered and the relative dose intensity was 89. The toxicity was mild with 12 of grade III neutropenia and 14 of grade III/IV thrombocytopenia without clinical symptoms. The response rate was 20 (8/38), comprising two complete and six partial responses. The median response duration and overall survival were 9 (2–25) and 11 months, respectively. The overall survival of 12 months was better in the third line patients than the 7 months in the fourth line treatment group.
Gemcitabine monotherapy is effective and safe as salvage treatment in heavily pretreated, breast cancer patients.
Keywordsbreast cancer gemcitabine heavily pretreated monotherapy salvage
Unable to display preview. Download preview PDF.
- 1.Fossati, R, Confalonieri, C, Torri, V, Ghislandi, E, Penna, A, Pistotti, V, Tinazzi, A, Liberati, A 1998Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 womenJ Clin Oncol6034393460Google Scholar
- 2.Valagussa, P, Tancini, G, Bonadonna, G 1986Salvage treatment of patients suffering relapse after adjuvant CMF chemotherapyCancer5814111417Google Scholar
- 3.Bishop, JF, Dewar, J, Toner, GC, Smith, J, Tattersall, MH, Olver, IN, Ackland, S, Kennedy, I, Goldstein, D, Gurney, H, Walpole, E, Levi, J, Stephenson, J, Canetta, R 1999Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancerJ Clin Oncol1723552364Google Scholar
- 4.Carmichael, J, Possinger, K, Phillip, P, Beykirch, M, Kerr, H, Walling, J, Harris, AK 1995Advanced breast cancer: a phase II trial with gemcitabineJ Clin Oncol1327312736Google Scholar
- 5.Blum, JL, Jones, SE, Buzdar, AU, LoRusso, PM, Kuter, I, Vogel, C, Osterwalder, B, Burger, HU, Brown, CS, Griffin, T 1999Multicenter phase II study of capecitabine in paclitaxel-regractory metastatic breast cancerJ Clin Oncol17485493Google Scholar
- 6.Fumoleau, P, Delgado, FM, Delozier, T, Monnier, A, Gil Delgado, MA, Kerbrat, P, Garcia-Giralt, E, Keiling, R, Namer, M, Closon, MT 1993Phase II trial of biweekly intravenous vinorelbine as first line advanced breast cancer chemotherapyJ Clin Oncol1112451252Google Scholar
- 7.Vogel, CL, Cobleigh, MA, Tripathy, D, Gutheil, JC, Harris, LN, Fehrenbacher, L, Slamon, DJ, Murphy, M, Novotny, WF, Burchmore, M, Shak, S, Stewart, SJ, Press, M 2002Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancerJ Clin Oncol20719726Google Scholar
- 8.Joensuu, H, Holli, K, Heikkinen, M, Suonio, E, Aro, AR, Hietanen, P, Huovinen, R 1998Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trialJ Clin Oncol1637203730Google Scholar
- 9.Norris, B, Pritchard, KI, James, K, Myles, J, Bennett, K, Marlin, S, Skillings, J, Findlay, B, Vandenberg, T, Goss, P, Latreille, J, Rudinskas, L, Lofters, W, Trudeau, M, Osoba, D, Rodgers, A 2000Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer. National Cancer Institute of Canada Clinical Trials Group Study MA8J Clin Oncol1823852394Google Scholar
- 10.Nabholtz, JM, Senn, HJ, Bezwoda, WR, Melnychuk, D, Deschenes, L, Douma, J, Vandenberg, TA, Rapoport, B, Rosso, R, Trillet-Lenoir, V, Drbal, J, Molino, A, Nortier, JWR, Richel, DJ, Nagykalnai, T, Siedlecki, P, Wilking, N, Genot, JY, Hupperets, PSGJ, Pannuti, F, Skarlos, D, Tomiak, EM, Murawsky, M, Alaki, M, Riva, A, Aapro, M 1999For the 3–4 study group: prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapyJ Clin Oncol1714131424Google Scholar
- 11.Sledge, GW, Neuberg, D, Bernardo, P, Ingle, JN, Martino, S, Rowinsky, EK, Wood, WC 2003Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer. An intergroup trialJ Clin Oncol21588592Google Scholar
- 12.Anderson, H, Lund, B, Bach, F, Thatcher, N, Walling, J, Hansen, HH 1994Single agent activity of weekly gemcitabine in advanced non-small cell lung cancer: a phase II studyJ Clin Oncol1218211826Google Scholar
- 13.Lund, B, Hansen, OP, Theilade, K, Hansen, M, Neijt, JP 1994Phase II study of gemcitabine (2′,2′-difluorodeoxycytidine) in previously treated ovarian cancerJ Natl Cancer Inst8615301533Google Scholar
- 14.O’Rourke, TJ, Brown, TD, Havlin, K, Kuhn, JG, Craig, JB, Burris, HA, Satterlee, WG, Tarassoff, PG, Von Hoff, DD 1994Phase I clinical trial of gemcitabine given as an intravenous bolus on 5 consecutive daysEur J Cancer30417418Google Scholar
- 15.Abbruzzese, JL, Grunewald, R, Weeks, EA, Gravel, D, Adams, T, Nowak, B, Mineishi, S, Tarassoff, P, Satterlee, W, Raber, MN 1991A phase I clinical, plasma, and cellular pharmacology study of gemcitabineJ Clin Oncol9491498Google Scholar
- 16.Luftner, D, Flath, B, Akrivakis, C, Grunewald, R, Mergenthaler, HG, Possinger, K 1998Gemcitabine for palliative treatment in metastatic breast cancerJ Cancer Res Clin Oncol124527531Google Scholar
- 17.Seidman, AD 2001Gemcitabine as single-agent therapy in the management of advanced breast cancerOncology151114Google Scholar
- 18.Nagourney, RA, Link, JS, Blitzer, JB, Forsthoff, C, Evans, SS 2000Gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed breast cancer patientsJ Clin Oncol1822452249Google Scholar
- 19.Mavroudis, D, Malamos, M, Alexopoulos, A, Kourousis, C, Agelaki, A, Sarra, E, Potamianou, A, Kosmas, C, Rigatos, G, Giannakakis, T, Kalbakis, K, Apostolaki, F, Vlachonicolis, J, Kakolyris, S, Samonis, G, Georgoulias, V 1999For the Greek breast cooperative group: salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: a multicenter phase II trialAnn Oncol10211215Google Scholar
- 20.Geels, P, Eisenhauer, E, Bezjak, A, Zee, B, Day, A 2000Palliative effect of chemotherapy: objective tumor response is associated with symptom improvement in patients with metastatic breast cancerJ Clin Oncol1823952405Google Scholar
- 21.Park, JY, Kim, C, Sohn, JH, Kim, YT, Rha, SY, Jang, WI, Kim, GE, Chung, HC 2002A phase II study of gemcitabine monotherapy in breast cancer patients refractory to anthracycline and taxaneCancer Res Treat34274279Google Scholar
- 22.Blackstein, M, Vogel, CL, Ambinder, R, Cowan, J, Iglesias, J, Melemed, A. 1997Phase II study of gemcitabine in patients with metastatic breast cancerEur J Cancer33S149Google Scholar
- 23.Spielmann, M, Llombart-Cussac, A, Kalla, S, Espie, M, Namer, M, Ferrero, JM, Dieras, V, Fumoleau, P, Cuvier, C, Perrocheau, G, Ponzio, A, Kayitalire, L, Pouillart, P 2001Single-agent gemcitabine is active in previously treated metastatic breast cancerOncology60303307Google Scholar
- 24.Stathopoulos, GP, Rigatos, SK, Pergantas, N, Tsavdarides, D, Athanasiadis, I, Malamos, NA, Stathopoulos, JG 2002Phase II trial of biweekly administration of vinorelbine and gemcitabine in pretreated advanced breast cancerJ Clin Oncol203741Google Scholar
- 25.Madajewicz, S, Hentschel, P, Burns, P, Caruso, R, Fiore, J, Fried, M, Malhotra, H, Ostrow, S, Sugarman, S, Viola, M 2000Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignanciesJ Clin Oncol18353357Google Scholar
- 26.Conte, P, Cetto, GL, Crino, L 2001The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancerOncology154143Google Scholar
- 27.Sanchez-Rovira, P, Jaen, A, Gonzalez, E, Carrasco, E 2001Biweekly gemcitabine, doxorubicin, and paclitaxel as first-line treatment in metastatic breast cancerOncology154447Google Scholar
- 28.Miller, KD, Sisk, J, Ansari, R 2001Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancerOncology153840Google Scholar
- 29.Carmichael, J, Walling, J 1996Phase II activity of gemcitabine in advanced breast cancerSemin Oncol237781Google Scholar