Taxanes in the Adjuvant Treatment of Breast Cancer

Adjuvant chemotherapy clearly demonstrates a reduction in mortality in breast cancer. However, the added benefit from the addition of taxanes remains uncertain. Paclitaxel and its cousin docetaxel have proven activity in the treatment of metastatic breast cancer. Toxicity has been tolerable when taxanes are used as single agents or in combination with anthracyclines. Several clinical trials are currently underway evaluating the role of taxanes in the adjuvant setting. Preliminary results from large phase III studies are promising; however, mature data are required before conclusions can be drawn. This article reviews the trials currently underway, evaluating the efficacy, dosage, scheduling, and regimens of taxanes in the adjuvant treatment of breast cancer.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Lori J. Goldstein, MD, Director, Breast Evaluation Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111-2412. E-mail: lj_Goldstein@fccc.edu

References

  • 1

    Early Breast Cancer Trialists' Collaborative Group. Effects of radiotherapy and surgery in early breast cancer – An overview of the randomized trials. N Engl J Med1995;333:14441456.

    • Search Google Scholar
    • Export Citation
  • 2

    Early Breast Cancer Trialists'Collaborative Group. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. An overview of 61 randomized trials among 28,896 women. N Engl J Med1988;319:16811692.

    • Search Google Scholar
    • Export Citation
  • 3

    Early Breast Cancer Trialists' Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. 133 Randomized trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet1992;339:7185.

    • Search Google Scholar
    • Export Citation
  • 4

    Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer: An overview of the randomized trials. Lancet1998;352:930942.

    • Search Google Scholar
    • Export Citation
  • 5

    HortobagyiGNBuzdarAU. Present status of anthracyclines in the adjuvant treatment of breast cancer. Drugs1993; 45(Suppl 2):1019.

  • 6

    NabholtzJMGelmonKBontenbalM. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol1996;14:18581867.

    • Search Google Scholar
    • Export Citation
  • 7

    SeidmanAHudisCAAlbanelJ. Dose–dense therapy with weekly 1–hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol2001;19:42164223.

    • Search Google Scholar
    • Export Citation
  • 8

    PerezEAVogelCLIrwinDH. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol2001;19:42164223.

    • Search Google Scholar
    • Export Citation
  • 9

    HendersonICBerryDDemetriG. Improved disease free survival 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.

    • Search Google Scholar
    • Export Citation
  • 10

    SchiffPFantJHorowitzS. Promotion of microtubule assembly in vitro by taxol. Nature1979;227:665667.

  • 11

    ParnessJHoroxitzSB. Taxol binds to polymerized tubulin in vitro. J Cell Biol1981;91:497487.

  • 12

    TishlerRSchiffPGeardCR. Taxol: A novel radiation sensitizer. Int J Radiat Oncol Biol Phys22:613617.

  • 13

    ChoyHRodriquezFWilcoxB. Radiation sensitizing effects of Taxotere (RP56976) (Abstr. #2991). Proc Am Assoc Cancer Res1992;33:500.

  • 14

    BurkhartCBermanJSwindellC. Relationship between the structure of taxol and other taxanes ion induction of TNF gene expression and cytotoxicity. Cancer Res1994;54:57795782.

    • Search Google Scholar
    • Export Citation
  • 15

    BelottiDVerganiVDrudisT. The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res1996;2:18431849.

  • 16

    SparreboomAvan TellingenONooijenWJ. Preclinical pharmacokinetics of paclita el and docetaxel. Anticancer Drugs1998;9:117.

  • 17

    BrunoRHilleDRivaA. Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol1998;16:187196.

    • Search Google Scholar
    • Export Citation
  • 18

    DiazJAndreuJ. Assembly of purified GDP–tubulin into mictotubules induced by RP56976 and paclitaxel: Reversibility, ligand stoidhiometry and competition. Biochemistry1993;32:27472755.

    • Search Google Scholar
    • Export Citation
  • 19

    FromesYGounanPBisseryMC. Differential effects of Taxol or Taxotere on tau or MAP2 containing microtubules (Abstr. #3055). Proc Am Assoc Cancer Res1992;33:511.

    • Search Google Scholar
    • Export Citation
  • 20

    WaniMCTaylorHLWallME. Plant antitumor agents. VI. The isolation and structure of Taxol, a novel antileukemic and antitumor agent from Taxux brevifolia. J Am Chem Soc1971;93:23252327.

    • Search Google Scholar
    • Export Citation
  • 21

    McGuireWPRowinskyEKRosensheinNB. Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med1989;111:273279.

    • Search Google Scholar
    • Export Citation
  • 22

    RowinskyEKDonehowerRC. Paclitaxel (Taxol). N Engl J Med1995;332:10041014.

  • 23

    HolmesFAWaltersRSTheriaultRL. Phase II trial of Taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst1991;83:17971805.

    • Search Google Scholar
    • Export Citation
  • 24

    ReichmanBSSeidmanADCrownAP. Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol1993;11:19431951.

    • Search Google Scholar
    • Export Citation
  • 25

    SeidmanATierstenAHudesC. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol1995; 13:25752581.

    • Search Google Scholar
    • Export Citation
  • 26

    SeidmanADReichmanBSCrownJP. Paclitaxel as second and subsequent therapy for metastatic breast cancer: Activity independent of prior anthracycline exposure. J Clin Oncol1995;13:11521159.

    • Search Google Scholar
    • Export Citation
  • 27

    HolmesFAValeroVBuzdarAU. Final results: Randomized Phase III tral of paclitaxel by 3-hr infusion vs 96-hr infusion in patients with metastatic breast cancer (MBC). The long and short of it (Abstr). Proc Am Soc Clin Oncol1998;17:110a.

    • Search Google Scholar
    • Export Citation
  • 28

    AbramsJSVenaDABaltzJ. Paclitaxel activity in heavily pretreated breast cancer: A National Cancer Institute treatment referral center trail. J Clin Oncol1995;13: 20562065.

    • Search Google Scholar
    • Export Citation
  • 29

    CognettiFAloeANardiM. Low activity of paclitaxel in patients with metastatic breast cancer resistant to anthracyclines (Abstr. #227). Proc Am Soc Clin Oncol1996; 15:140a.

    • Search Google Scholar
    • Export Citation
  • 30

    NabholtzJMGelmonKBontenbalM. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol1996; 14:18581867.

    • Search Google Scholar
    • Export Citation
  • 31

    GianniLMunzoneECapriG. Paclitaxel in metastatic breast cancer: A trial of two doses by a 3-hour infusion in patients with disease recurrence after prior therapy with anthracyclines. J Natl Cancer Inst1995;87:11691175.

    • Search Google Scholar
    • Export Citation
  • 32

    WinerEBerryDDugganD. Failure of higher dose paclitaxel to improve outcome in patients with metastatic breast cancer. Results from CALGB 9342 (Abstr. #388). Proc Am Soc Clin Oncol1998;17:101a.

    • Search Google Scholar
    • Export Citation
  • 33

    SeidmanADHudisCAAlbanelJ. Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol199;16:33533361.

    • Search Google Scholar
    • Export Citation
  • 34

    PerezEAVogelCLIrwinDH. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol2001;19:42164223.

    • Search Google Scholar
    • Export Citation
  • 35

    RingelIHorowitzB. Studies with RPR56976 (Taxotere) a semisynthetic analogue of Taxol. J Natnl Cancer Inst1991;83:228291.

  • 36

    LavelleFBisseryMCCombeauC. Preclinical evaluation of docetaxel (Taxotere). Semin Oncol1995;22(Suppl 4):316.

  • 37

    ChevallierBFumolequPKerbratP. 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 Oncol1995;13:314322.

    • Search Google Scholar
    • Export Citation
  • 38

    FumoeauPChevallierBKerbratP. A multicenter phase II study of the efficacy and safety of docetaxel as first–line treatment of advanced breast cancer: Report of the Clinical Screening Group of the EOORTC. Ann Oncol1996; 7:165171.

    • Search Google Scholar
    • Export Citation
  • 39

    TrudeauMEEisenhauerEAHigginsBP. Docetaxel in patients with metastatic breast cancer: A phase II study of the National Cancer Institute of Canada – Clinical Trials Group. J Clin Oncol1996;14:422428.

    • Search Google Scholar
    • Export Citation
  • 40

    AlexopoulosCRigatosGEfremidisAP. A phase II study of the effectiveness of docetaxel (Taxotere) in women with advanced breast cancer previously teated with polychemotherapy. Hellenic Cooperation Interhospital Group in Oncology. Cancer Chemother Pharmacol1999;44: 253258.

    • Search Google Scholar
    • Export Citation
  • 41

    RavdinPMBurrisHACookG. Phase II trial of docetaxel in advanced anthracycline–resistant or anthracenedione–resistant breast cancer. J Clin Oncol1995;1328792885.

    • Search Google Scholar
    • Export Citation
  • 42

    AlexandreJBleuzenPBonneterreJ. Factors predicting for efficacy and safety of docetaxel in a compassionate–use cohort of 825 heavily pretreated advanced breast cancer patients. J Clin Oncol200;18:562573.

    • Search Google Scholar
    • Export Citation
  • 43

    ValeroVJonesSEVon HoffDD. A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer. J Clin Oncol1998;16:33623368.

    • Search Google Scholar
    • Export Citation
  • 44

    BurnsteinHJManolaJYoungerJ. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol2000;18:12121219.

  • 45

    MartinMLluchAOjedaB. Paclitaxel plus doxorubicin in metastatic breast cancer: Preliminary analysis of cardiotoxicity. Semin Oncol1997;24(Suppl 17):2630.

    • Search Google Scholar
    • Export Citation
  • 46

    GianniLMunzoneECapriG. 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 Oncol1996;13:26882699.

    • Search Google Scholar
    • Export Citation
  • 47

    DombernowskyPBehlJBoesgaardM. Doxorubicin plus paclitaxel in advanced breast cancer. Semin Oncol1997;24(Suppl 17)2630.

  • 48

    HortobagyiGNHolmesFA. Combination chemotherapy with paclitaxel and doxorubicin for metastatic breast cancer. Semin Oncol1997;24(Suppl 11):1319.

    • Search Google Scholar
    • Export Citation
  • 49

    HolmesFAMaddenTNewmanRA. Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer. J Clin Oncol1996;14:27132721.

    • Search Google Scholar
    • Export Citation
  • 50

    ValagussaPGianniLCapriG. Three-year follow-up in women with metastatic breast cancer after bolus doxorubicin and paclitaxel infused over 3 hours (Abstr. #429). Proc Am Soc Clin Oncol1998;17:111a.

    • Search Google Scholar
    • Export Citation
  • 51

    HainsworthJDJonesSEMennelRG. Paclitaxel with mitoxantrone, fluorouracil, and high-dose leucovorin in the treatment of metastatic breast cancer: A phase II trial. J Clin Oncol1996;14:16111616.

    • Search Google Scholar
    • Export Citation
  • 52

    MissetJDierasVBozecL. Long term follow up of the phase I/II study of docetaxel and doxorubicin as 1st line chemotherapy of metastatic breast cancer (Abstr. #613). Proc Am Soc Clin Oncol1998;17:160a.

    • Search Google Scholar
    • Export Citation
  • 53

    NabholtzJMMackeyJRSmylieM. Phase II study of docetaxel, doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. J Clin Oncol2001;19:314321.

    • Search Google Scholar
    • Export Citation
  • 54

    NabholtzJMNorthSSmylieM. Docetael (Taxotere) in combination with anthracyclines in the treatment of breast cancer. Semin Oncol2000;27(Suppl 3):1118.

    • Search Google Scholar
    • Export Citation
  • 55

    EisenhauerEAten Bokkel HuininkWWSwenertonK: European-Canadian randomized trail of paclitaxel in relapsed ovarian cancer: High dose versus low dose and long versus short infusion. J Clin Oncol1994;12:26542666.

    • Search Google Scholar
    • Export Citation
  • 56

    WeissRBDonehowerRCWiernikPH. Hypersensitivity reactions from Taxol. J Clin Oncol1990;8: 12631268.

  • 57

    RowinskyEKEisenhauerEAChardhryV. Clinical toxicities encountered with paclitaxel(Taxol). Semin Oncol1993;20(Suppl 3):115.

  • 58

    DavidsonNG. Single-agent paclitaxel as first-line treatment of metastatic breast cancer: The British experience. Semin Oncol1996;23(Suppl 11):610.

    • Search Google Scholar
    • Export Citation
  • 59

    RowinskyEKMcGuireWPGuarnieriT. Cardiac disturbances during the administration of taxol. J Clin Oncol1991;9:17041712.

  • 60

    ArbuckSGStraussHRowinskyE. A reassessment of the cardiac toxicity associated with Taxol. Monogr Natl Cancer Inst1993;15:117130.

  • 61

    SteinMDrumeaKAbo-RamsiR. Taxol induced cellulites after extravasation: A rarely reported event. Am J Clin Oncol1997;20:540.

  • 62

    ValeroVHolmesFAWaltersRS. Phase II trial of docetaxel: A new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer. J Clin Oncol1995;13:28862894.

    • Search Google Scholar
    • Export Citation
  • 63

    DemetriGBerryDYoungerJ. Dose-intensified cyclophosphamide/doxorubicin followed by Taxol as adjuvant systemic chemotherapy for node-positive breast cancer (CALGB 9141): Randomized comparison of two dose levels of G-CSF (Abstr. #63). Proc Am Soc Clin Oncol1994; 13:65.

    • Search Google Scholar
    • Export Citation
  • 64

    HendersonICBerryDDemetriG. Improved disease-free and overall survival from the addition of sequential paclitaxel but not from the escalation of docorubicin dose level in the adjuvant chemotherapy of patients with node-positive primary breast cancer (Abstr). Proc Am Soc Clin Oncol1998;17:101.

    • Search Google Scholar
    • Export Citation
  • 65

    EifelPAxelsonJACostaJ. National Institutes of Health Consensus Development Conference Statement: Adjuvant therapy for breast cancer, November 1-3 2000. J Natl Cancer Inst2001;93:979. www.consensus.nih.gov

    • Search Google Scholar
    • Export Citation
  • 66

    HendersonICBerryDADemitriG. Improved outcomes from adding paclitaxel but not from escalating doxorubicin dose in adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol2003; 10 (in press).

    • Search Google Scholar
    • Export Citation
  • 67

    HendersonIC. NIH Consensus Development Conference 2000.www.sabes.org

  • 68

    ThomasEBuzdarATheriaultR. Role of paclitaxel in adjuvant therapy of operable breast cancer: Preliminary results of a prospective randomized clinical trial (Abstr). Proc Am Soc Clin Oncol2000;19:74a.

    • Search Google Scholar
    • Export Citation
  • 69

    MamounasEP. NSABP protocol B-27: Preoperative doxorubicin plus cyclophosphamide followed by preoperative or postoperative docetaxel. Oncology1997;11(Suppl 6):3740.

    • Search Google Scholar
    • Export Citation
  • 70

    MamounasEP. Overview of National Surgical Adjuvant Breast Project neoadjuvant chemotherapy studies. Semin Oncol1998;25(Suppl 3):3135.

    • Search Google Scholar
    • Export Citation
  • 71

    NSABP. The effect on primary tumor response of adding sequential Taxotere to adriamycin and cyclophosphamide: Preliminary results from NSABP protocol B-27 (Abstr. #5). San Antonio Breast Cancer Symposium2001. www.sabes.org

    • Search Google Scholar
    • Export Citation
  • 72

    HutcheonAWHeysSDMillerID. Improvements in survival in patients receiving primary chemotherapy with docetaxel for breast cancer. A randomized controlled trial (Abstr. #506). San Antonio Breast Cancer Symposium2001.

    • Search Google Scholar
    • Export Citation
  • 73

    GianniLMunzoneECapriG. 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 Oncol1995;13:26882699.

    • Search Google Scholar
    • Export Citation
  • 74

    HolmesFAValeroVWaltersRS. Paclitaxel by 24 hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: Phase I results. Ann Oncol1999;10:403411.

    • Search Google Scholar
    • Export Citation
  • 75

    BergSLCowanKHBalisFM. Pharmacokinetics of Taxol and doxorubicin administered alone and in combination by continuous 72–hour infusion. J Natl Cancer Inst1994;36;143145.

    • Search Google Scholar
    • Export Citation
  • 76

    GianniLBiganoLLocatelliA. Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel inpatients with breast cancer. J Clin Oncol1997;15:19061915.

    • Search Google Scholar
    • Export Citation
  • 77

    SchullerICzejkaMKletzlH. Doxorubicin and Taxotere: A pharmacokinetic study of the combination in advanced breast cancer (Abstr. #790). Proc Am Soc Clin Oncol1998;17:205a.

    • Search Google Scholar
    • Export Citation
  • 78

    CitronMBerryDCirrincioneCCarpenterJ. Superiority of dose-dense (DD) over conventional scheduling (CS) and equivalence of sequential (SC) vs. combination adjuvant chemotherapy (CC) for node-positive breast cancer (CALGB 9741, INT C9741) (Abstr. #15). San Antonio Breast Cancer Symposium2002.

    • Search Google Scholar
    • Export Citation
  • 79

    NabholtzJMPienkowskiTMackeyJ. Phase III trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer (BC) patients: Interim analysis of the VCIRG 001 study (Abstr. #141). Proc Am Soc Clin Oncol2002;21:36a.

    • Search Google Scholar
    • Export Citation
  • 80

    CobleighMAVogelCLTripathyD. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-expressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol1999;17: 26392648.

    • Search Google Scholar
    • Export Citation
  • 81

    NCCN Practice Guidelines in Oncology v.2.2003. Breast Cancer Treatment Guidelines.www.nccn.org

  • 82

    National Institutes of Health Consensus Development Panel. National Institutes of Health Consensus Development Conference Statement: Adjuvant Therapy for Breast Cancer, November 1-3, 2000. J Nat Cancer Inst2001;93:979989.

    • Search Google Scholar
    • Export Citation

Article Information

PubMed

Google Scholar

Related Articles

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 49 49 26
PDF Downloads 9 9 0
EPUB Downloads 0 0 0