Skip to main content

Advertisement

Log in

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

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

Abstract

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.

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

Access this article

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

  • HJ Luck C Thomssen M Untch W Kuhn H Eidtmann A du Bois S Olbricht V Moebus D Steinfeld T Bauknecht W Schroeder C Jackisch (2000) ArticleTitleMulticentric 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 19 280

    Google Scholar 

  • JM Nabholtz C Falkson D Campos J Szanto M Martin S Chan T Pienkowski J Zaluski T Pinter M Krzakowski D Vorobiof R Leonard I Kennedy N Azli M Murawsky A Riva P Pouillart (2003) ArticleTitleTAX 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 trial J Clin Oncol 21 968–975 Occurrence Handle1:CAS:528:DC%2BD2cXpsVGqs7g%3D Occurrence Handle12637459

    CAS  PubMed  Google Scholar 

  • J Jassem T Pienkowski A Pluzanska S Jelic V Gorbunova Z Mrsic-Krmpotic J Berzins T Nagykalnai N Wigler J Renard S Munier C Weil (2001) ArticleTitleCentral & 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 trial J Clin Oncol 19 1707–1715 Occurrence Handle1:CAS:528:DC%2BD3MXisFygs70%3D Occurrence Handle11251000

    CAS  PubMed  Google Scholar 

  • P Reichardt G Minckwitz ParticleVon PC Thuss-Patience W Jonat H Kolbl F Janicke DG Kieback W Kuhn AE Schindler S Mohrmann M Kaufmann HJ Luck (2003) ArticleTitleMulticenter phase II study of oral capecitabine (Xeloda) in patients with metastatic breast cancer relapsing after treatment with a taxane-containing therapy Ann Oncol 14 1227–1233 Occurrence Handle1:STN:280:DC%2BD3szkvVaruw%3D%3D Occurrence Handle12881384

    CAS  PubMed  Google Scholar 

  • J Crown V Dieras M Kaufmann G Minckwitz Particlevon S Kaye R Leonard M Marty JL Misset B Osterwalder M Piccart (2002) ArticleTitleChemotherapy for metastatic breast cancer-report of a European expert panel Lancet Oncol 3 719–727 Occurrence Handle1:CAS:528:DC%2BD38XptlSqsLg%3D Occurrence Handle12473512

    CAS  PubMed  Google Scholar 

  • CS Hill R Treisman (1995) ArticleTitleTranscriptional regulation by extracellular signals; mechanisms and specificity Cell 80 199–211 Occurrence Handle1:CAS:528:DyaK2MXjtlGnsr0%3D Occurrence Handle7834740

    CAS  PubMed  Google Scholar 

  • G Minckwitz Particlevon M Kaufmann H Schmid K Goerttler G Bastert (1993) ArticleTitleEpidermal growth factor receptor and S-phase fraction as prognosticator combination in node negative primary breast cancer The Breast 2 229–233

    Google Scholar 

  • JRC Sainsbury JR Farndon GK Needham AJ Malcolm AL Harris (1987) ArticleTitleEpidermal growth factor receptor status as predictor of early recurrence of and death from breast cancer Lancet 1 1398–1402 Occurrence Handle1:STN:280:DyaL2s3islOqtw%3D%3D Occurrence Handle2884496

    CAS  PubMed  Google Scholar 

  • Kelly H, Ferry D, Hammond L, Kris M, Rowinsky E, Ranson M: Proc AACR, San Francisco, p 3896, 2000

  • RS Herbst AM Maddox ML Rothenberg EJ Small EH Rubin J Baselga F Rojo WK Hong H Swaisland SD Averbuch J Ochs PM LoRusso (2002) ArticleTitleSelective 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 trial J Clin Oncol 20 3815–3825 Occurrence Handle1:CAS:528:DC%2BD38XntVyns7s%3D Occurrence Handle12228201

    CAS  PubMed  Google Scholar 

  • J Baselga D Rischin M Ranson H Calvert E Raymond DG Kieback SB Kaye L Gianni A Harris T Bjork SD Averbuch A Feyereislova H Swaisland F Rojo J Albanell (2002) ArticleTitlePhase 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 types J Clin Oncol 20 4292–3402 Occurrence Handle10.1200/JCO.2002.03.100 Occurrence Handle1:CAS:528:DC%2BD38Xpt1CjtLo%3D Occurrence Handle12409327

    Article  CAS  PubMed  Google Scholar 

  • MJ Brady DF Cella F Mo AE Bonomi DS Tulsky SR Lloyd S Deasy M Cobleigh G Shiomoto (1997) ArticleTitleReliability and validity of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality of life instrument J Clin Oncol 15 974–986 Occurrence Handle1:STN:280:DyaK2s3htlyntQ%3D%3D Occurrence Handle9060536

    CAS  PubMed  Google Scholar 

  • DF Cella DS Tulsky G Gray B Sarafian E Linn A Bonomi et al. (1993) ArticleTitleThe Functional Assessment of Cancer Therapy Scale; development and validation of the general measure J Clin Oncol 11 570–579 Occurrence Handle1:STN:280:DyaK3s7oslKqsQ%3D%3D Occurrence Handle8445433

    CAS  PubMed  Google Scholar 

  • LJ Fallowfield M Baum GP Magquire (1987) ArticleTitleDo psychological studies upset patients?> J Royal Soc Med 80 59 Occurrence Handle1:STN:280:DyaL2s7mvFGnug%3D%3D

    CAS  Google Scholar 

  • P Therasse SG Arbuck EA Eisenhauer J Wanders RS Kaplan L Rubinstein J Verweij M Glabbeke ParticleVan AT Oosterom Particlevan MC Christian SG Gwyther (2000) ArticleTitleNew 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 Canada J Natl Cancer Inst 92 205–216 Occurrence Handle10.1093/jnci/92.3.205 Occurrence Handle1:STN:280:DC%2BD3c7it1Gitg%3D%3D Occurrence Handle10655437

    Article  CAS  PubMed  Google Scholar 

  • M Fukuoka S Yano G Giaccone T Tamura K Nakagawa J Douillard et al. (2003) ArticleTitleMulti-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer J Clin Oncol 21 2237–2246 Occurrence Handle10.1200/JCO.2003.10.038 Occurrence Handle12748244 Occurrence Handle1:CAS:528:DC%2BD2cXpsVGqu7w%3D

    Article  PubMed  CAS  Google Scholar 

  • M Kris RB Natale R Herbst T Lynch D Prager C Belani et al. (2003) ArticleTitleEfficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial JAMA 290 2149–2158 Occurrence Handle10.1001/jama.290.16.2149 Occurrence Handle1:CAS:528:DC%2BD3sXosVOnsbo%3D Occurrence Handle14570950

    Article  CAS  PubMed  Google Scholar 

  • K Albain R Elledge WJ Gradishar DF Hayes E Rowinsky C Hudis L Pusztai D Tripathy S Modi S Rubi (2002) ArticleTitleOpen-label, phase II, multicenter trial of ZD1839 (“Iressa”) in patients with advanced breast cancer Breast Cancer Res Treat 76 S33

    Google Scholar 

  • J Baselga J Albanell A Ruiz A Lluch P Gascon S Gonzalez V Guillen S Sauleda S Averbuch (2003) ArticleTitlePhase II and tumor pharmacodynamic study of gefinitib (ZD1839) in patients with advanced breast cancer Proc Am Soc Clin Oncol 22 7

    Google Scholar 

  • AD Seidman J O’Shaughnessy JL Misset (2002) ArticleTitleSingle-agent capecitabine: a reference treatment for taxane-pretreated metastatic breast cancer The Oncologist 7 20–28 Occurrence Handle1:CAS:528:DC%2BD3sXksV2itQ%3D%3D Occurrence Handle12454316

    CAS  PubMed  Google Scholar 

  • CL Vogel MA Cobleigh D Tripathy JC Gutheil LN Harris L Fehrenbacher DJ Slamon M Murphy WF Novotny M Burchmore S Shak SJ Stewart (2002) ArticleTitlePress M Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer J Clin Oncol 20 719–726 Occurrence Handle10.1200/JCO.20.3.719 Occurrence Handle11821453 Occurrence Handle1:CAS:528:DC%2BD38XhsVGmt7o%3D

    Article  PubMed  CAS  Google Scholar 

  • M Ranson (2002) ArticleTitleZD1839 (Iressa™): for more than just non-small cell lung cancer. Oncologist 7 16–24 Occurrence Handle1:CAS:528:DC%2BD38XnsFOiuro%3D Occurrence Handle12202784

    CAS  PubMed  Google Scholar 

  • A Schneeweiss S Kolay S Aulmann G Minckwitz ParticleVon J Torode M Koehler G Bastert (2004) ArticleTitleInduction of remission in a patient with metastatic breast cancer refractory to trastuzumab and chemotherapy following treatment with gefitinib (‘Iressa’, ZD1839) Anticancer Drugs 15 235–238 Occurrence Handle1:CAS:528:DC%2BD2cXjslWqtLk%3D Occurrence Handle15014356

    CAS  PubMed  Google Scholar 

  • JM Gee ME Harper IR Hutcheson TA Madden D Barrow JM Knowlden RA McClelland N Jordan AE Wakeling RI Nicholson (2003) ArticleTitleThe antiepidermal growth factor receptor agent gefitinib (ZD1839/Iressa) improves antihormone response and prevents development of resistance in breast cancer in vitro Endocrinology 144 5105–5117 Occurrence Handle1:CAS:528:DC%2BD3sXosleqsr0%3D Occurrence Handle12960029

    CAS  PubMed  Google Scholar 

  • S Okubo J Kurebayashi T Otsuki Y Yamamoto K Tanaka H Sonoo (2004) ArticleTitleAdditive 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 cells Br J Cancer 90 236–244 Occurrence Handle1:CAS:528:DC%2BD2cXhtFKmsg%3D%3D Occurrence Handle14710235

    CAS  PubMed  Google Scholar 

  • J Shou S Massarweh CK Osborne AE Wakeling S Ali H Weiss R Schiff (2004) ArticleTitleMechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer J Natl Cancer Inst 96 926–935 Occurrence Handle10.1093/jnci/djh166 Occurrence Handle1:CAS:528:DC%2BD2cXltVWmtLY%3D Occurrence Handle15199112

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gunter von Minckwitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

von Minckwitz, G., Jonat, W., Fasching, P. et al. A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer. Breast Cancer Res Treat 89, 165–172 (2005). https://doi.org/10.1007/s10549-004-1720-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-004-1720-2

Keywords

Navigation