Breast Cancer Research and Treatment

, Volume 89, Issue 2, pp 165–172 | Cite as

A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer

  • Gunter von MinckwitzEmail author
  • Walter Jonat
  • Peter Fasching
  • Andreas du Bois
  • Ulrich Kleeberg
  • Hans-Joachim Lück
  • Erika Kettner
  • Jörn Hilfrich
  • Wolfgang Eiermann
  • Julie Torode
  • Andreas Schneeweiss


Background. Epidermal growth factor receptor (EGFR) is considered to be a viable drug target in a variety of solid tumors. The clinical benefit and safety of the EGFR tyrosine kinase inhibitor gefitinib (‘Iressa’)1 was evaluated in this Phase II, multicentre study of patients with taxane and anthracycline pretreated, metastatic breast cancer. Methods. Gefitinib (500 mg/day) was given to 58 patients until disease progression. Primary endpoint was the clinical response rate to the study treatment. Results. One patient (1.7%) had objective partial tumor response of her liver and pleural metastasis. Fifty-seven patients (98.3%) were non-responders with 52 patients (89.7%) having progressive disease and five patients (8.6%) were not evaluable. Two patients reported a significant improvement in pain at metastatic sites (1 liver, 1 bone). The median time to progression was 61 days (95% CI : 54–82 days) and the proportion of patients alive and progression free at 6 months at trial closure was 1.8% (95% CI : 0.0–5.2%). The median survival time was 357 days (95% CI : 257–441 days). Fifty-four patients (93.1%) discontinued study medication prematurely due to disease progression and three (5.2%) due to adverse events (diarrhea, pruritus, peripheral edema). Conclusions. Gefitinib monotherapy at 500 mg daily did not appear to be efficacious in the treatment of heavily pretreated metastatic breast cancer patients. It was well tolerated and the side effect profile was as expected from current knowledge of the drug. There was no correlation between EGFR expression and response in this study.


gefitinib metastatic breast cancer phase II taxane-pretreated 


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  1. Luck, HJ, Thomssen, C, Untch, M, Kuhn, W, Eidtmann, H, du Bois, A, Olbricht, S, Moebus, V, Steinfeld, D, Bauknecht, T, Schroeder, W, Jackisch , C 2000Multicentric 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 Oncol19280Google Scholar
  2. Nabholtz, JM, Falkson, C, Campos, D, Szanto, J, Martin, M, Chan, S, Pienkowski, T, Zaluski, J, Pinter, T, Krzakowski, M, Vorobiof, D, Leonard, R, Kennedy, I, Azli, N, Murawsky, M, Riva, A, Pouillart, P 2003TAX 306 Study Group Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trialJ Clin Oncol21968975PubMedGoogle Scholar
  3. Jassem, J, Pienkowski, T, Pluzanska, A, Jelic, S, Gorbunova, V, Mrsic-Krmpotic, Z, Berzins, J, Nagykalnai, T, Wigler, N, Renard, J, Munier, S, Weil, C 2001Central & Eastern Europe and Israel Pacitaxel Breast Cancer Study Group. 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 trialJ Clin Oncol1917071715PubMedGoogle Scholar
  4. Reichardt, P, Minckwitz, G, Thuss-Patience, PC, Jonat, W, Kolbl, H, Janicke, F, Kieback, DG, Kuhn, W, Schindler, AE, Mohrmann, S, Kaufmann, M, Luck, HJ 2003Multicenter phase II study of oral capecitabine (Xeloda) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapyAnn Oncol1412271233PubMedGoogle Scholar
  5. Crown, J, Dieras, V, Kaufmann, M, Minckwitz, G, Kaye, S, Leonard, R, Marty, M, Misset, JL, Osterwalder, B, Piccart, M 2002Chemotherapy for metastatic breast cancer-report of a European expert panelLancet Oncol3719727PubMedGoogle Scholar
  6. Hill, CS, Treisman, R 1995Transcriptional regulation by extracellular signals; mechanisms and specificityCell80199211PubMedGoogle Scholar
  7. Minckwitz, G, Kaufmann, M, Schmid, H, Goerttler, K, Bastert, G 1993Epidermal growth factor receptor and S-phase fraction as prognosticator combination in node negative primary breast cancerThe Breast2229233Google Scholar
  8. Sainsbury, JRC, Farndon, JR, Needham, GK, Malcolm, AJ, Harris, AL 1987Epidermal growth factor receptor status as predictor of early recurrence of and death from breast cancerLancet113981402PubMedGoogle Scholar
  9. Kelly H, Ferry D, Hammond L, Kris M, Rowinsky E, Ranson M: Proc AACR, San Francisco, p 3896, 2000 Google Scholar
  10. Herbst, RS, Maddox, AM, Rothenberg, ML, Small, EJ, Rubin, EH, Baselga, J, Rojo, F, Hong, WK, Swaisland, H, Averbuch, SD, Ochs, J, LoRusso, PM 2002Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trialJ Clin Oncol2038153825PubMedGoogle Scholar
  11. Baselga, J, Rischin, D, Ranson, M, Calvert, H, Raymond, E, Kieback, DG, Kaye, SB, Gianni, L, Harris, A, Bjork, T, Averbuch, SD, Feyereislova, A, Swaisland, H, Rojo, F, Albanell, J 2002Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor typesJ Clin Oncol2042923402CrossRefPubMedGoogle Scholar
  12. Brady, MJ, Cella, DF, Mo, F, Bonomi, AE, Tulsky, DS, Lloyd, SR, Deasy, S, Cobleigh, M, Shiomoto, G 1997Reliability and validity of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality of life instrumentJ Clin Oncol15974986PubMedGoogle Scholar
  13. Cella, DF, Tulsky, DS, Gray, G, Sarafian, B, Linn, E, Bonomi, A,  et al. 1993The Functional Assessment of Cancer Therapy Scale; development and validation of the general measureJ Clin Oncol11570579PubMedGoogle Scholar
  14. Fallowfield, LJ, Baum, M, Magquire, GP 1987Do psychological studies upset patients?>J Royal Soc Med8059Google Scholar
  15. Therasse, P, Arbuck, SG, Eisenhauer, EA, Wanders, J, Kaplan, RS, Rubinstein, L, Verweij, J, Glabbeke, M, Oosterom, AT, Christian, MC, Gwyther, SG 2000New guidelines to evaluate the response to treatment in solid tumors European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of CanadaJ Natl Cancer Inst92205216CrossRefPubMedGoogle Scholar
  16. Fukuoka, M, Yano, S, Giaccone, G, Tamura, T, Nakagawa, K, Douillard, J,  et al. 2003Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung CancerJ Clin Oncol2122372246CrossRefPubMedGoogle Scholar
  17. Kris, M, Natale, RB, Herbst, R, Lynch, T, Prager, D, Belani, C,  et al. 2003Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trialJAMA29021492158CrossRefPubMedGoogle Scholar
  18. Albain, K, Elledge, R, Gradishar, WJ, Hayes, DF, Rowinsky, E, Hudis, C, Pusztai, L, Tripathy, D, Modi, S, Rubi, S 2002Open-label, phase II, multicenter trial of ZD1839 (“Iressa”) in patients with advanced breast cancerBreast Cancer Res Treat76S33(Suppl 1)Google Scholar
  19. Baselga, J, Albanell, J, Ruiz, A, Lluch, A, Gascon, P, Gonzalez, S, Guillen, V, Sauleda, S, Averbuch, S 2003Phase II and tumor pharmacodynamic study of gefinitib (ZD1839) in patients with advanced breast cancerProc Am Soc Clin Oncol227(abstr 24)Google Scholar
  20. Seidman, AD, O’Shaughnessy, J, Misset, JL 2002Single-agent capecitabine: a reference treatment for taxane-pretreated metastatic breast cancerThe Oncologist72028PubMedGoogle Scholar
  21. Vogel, CL, Cobleigh, MA, Tripathy, D, Gutheil, JC, Harris, LN, Fehrenbacher, L, Slamon, DJ, Murphy, M, Novotny, WF, Burchmore, M, Shak, S, Stewart, SJ 2002Press M Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancerJ Clin Oncol20719726CrossRefPubMedGoogle Scholar
  22. Ranson, M 2002ZD1839 (Iressa™): for more than just non-small cell lung cancer.Oncologist71624(Suppl 4)PubMedGoogle Scholar
  23. Schneeweiss, A, Kolay, S, Aulmann, S, Minckwitz, G, Torode, J, Koehler, M, Bastert, G 2004Induction of remission in a patient with metastatic breast cancer refractory to trastuzumab and chemotherapy following treatment with gefitinib (‘Iressa’, ZD1839)Anticancer Drugs15235238PubMedGoogle Scholar
  24. Gee, JM, Harper, ME, Hutcheson, IR, Madden, TA, Barrow, D, Knowlden, JM, McClelland, RA, Jordan, N, Wakeling, AE, Nicholson, RI 2003The antiepidermal growth factor receptor agent gefitinib (ZD1839/Iressa) improves antihormone response and prevents development of resistance in breast cancer in vitroEndocrinology14451055117PubMedGoogle Scholar
  25. Okubo, S, Kurebayashi, J, Otsuki, T, Yamamoto, Y, Tanaka, K, Sonoo, H 2004Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cellsBr J Cancer90236244PubMedGoogle Scholar
  26. Shou, J, Massarweh, S, Osborne, CK, Wakeling, AE, Ali, S, Weiss, H, Schiff, R 2004Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancerJ Natl Cancer Inst96926935CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Gunter von Minckwitz
    • 1
    Email author
  • Walter Jonat
    • 2
  • Peter Fasching
    • 3
  • Andreas du Bois
    • 4
  • Ulrich Kleeberg
    • 5
  • Hans-Joachim Lück
    • 6
  • Erika Kettner
    • 7
  • Jörn Hilfrich
    • 8
  • Wolfgang Eiermann
    • 9
  • Julie Torode
    • 10
  • Andreas Schneeweiss
    • 11
  1. 1.German Breast Group/Universitäts-Frauenklinik FrankfurtNeu-Isenburg/FrankfurtGermany
  2. 2.Klinik fuer Gynaekologie und GeburtshilfeUniversitaetsklinikum KielKiel
  3. 3.Klinik fuer FrauenheilkundeUniversitaetsklinikum ErlangenErlangen
  4. 4.Klinik fuer Gynaekologie und Gynaekologische OnkologieDr.-Horst-Schmidt-KlinikenWiesbaden
  5. 5.Haematologisch-onkologische Praxis AltonaHamburg
  6. 6.Abt. Gynaekologische OnkologieKrankenhaus Oststadt, Frauenklinik der MHHHannover
  7. 7.Haematologische AbteilungStaedtisches Klinikum MagdeburgMagdeburg
  8. 8.Standort Kirchrode, GynaekologieHenriettenstiftung Neu-BethesdaHannover
  9. 9.Frauenklinik vom Roten KreuzMunich
  10. 10.AstraZeneca GmbHWedel
  11. 11.Universitaetsklinikum HeidelbergFrauenklinik, HeidelbergGermany

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