Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2+ metastatic breast cancer

被引:95
作者
Jahanzeb, M
Mortimer, JE
Yunus, F
Irwin, DH
Speyer, J
Koletsky, AJ
Klein, P
Sabir, T
Kronish, L
机构
[1] Boca Raton Comprehens Canc Ctr, Boca Raton, FL USA
[2] Washington Univ, Sch Med, St Louis, MO 63130 USA
[3] Boston Baskin Canc Grp, Memphis, TN USA
[4] Alta Bates Comprehens Canc Ctr, Berkeley, CA USA
[5] NYU, Sch Med, New York, NY USA
[6] St Vincents Comprehens Canc Ctr, New York, NY USA
[7] Michigan Canc Specialists, Roseville, MI USA
关键词
immunohistochemistry; in situ hybridization; fluorescence; breast neoplasms; neutropenia;
D O I
10.1634/theoncologist.7-5-410
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. Patients and Methods. A phase 11, open-label trial of intravenous vinorelbine (30 mg/m(2) on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2(+) metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. Results. Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3(+) = 82% (18/22) response and IHC 2(+) = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity. Conclusions. Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2(+), metastatic breast cancer. Further investigation of this novel regimen is planned.
引用
收藏
页码:410 / 417
页数:8
相关论文
共 35 条
  • [1] VINORELBINE AS SINGLE-AGENT IN PRETREATED PATIENTS WITH ADVANCED BREAST-CANCER
    BARNI, S
    ARDIZZOIA, A
    BERNARDO, G
    VILLA, S
    STRADA, MR
    CAZZANIGA, M
    ARCHILI, C
    FRONTINI, L
    [J]. TUMORI, 1994, 80 (04) : 280 - 282
  • [2] Ongoing trials with trastuzumab in metastatic breast cancer
    Bell, R
    [J]. ANNALS OF ONCOLOGY, 2001, 12 : 69 - 73
  • [3] BERNS EMJJ, 1992, CANCER RES, V52, P1107
  • [4] BIANCO AR, 1998, P AN M AM SOC CLIN, V17, P97
  • [5] Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer
    Burstein, HJ
    Kuter, I
    Campos, SM
    Gelman, RS
    Tribou, L
    Parker, LM
    Manola, J
    Younger, J
    Matulonis, U
    Bunnell, CA
    Partridge, AH
    Richardson, PG
    Clarke, K
    Shulman, LN
    Winer, EP
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (10) : 2722 - 2730
  • [6] BURSTEIN HJ, 2002, P AN M AM SOC CLIN, V21, pA53
  • [7] CANOBBIO L, 1989, SEMIN ONCOL, V16, P33
  • [8] Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease
    Cobleigh, MA
    Vogel, CL
    Tripathy, D
    Robert, NJ
    Scholl, S
    Fehrenbacher, L
    Wolter, JM
    Paton, V
    Shak, S
    Lieberman, G
    Slamon, DJ
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (09) : 2639 - 2648
  • [9] VINORELBINE (NAVELBINE) AS A SALVAGE TREATMENT FOR ADVANCED BREAST-CANCER
    DEGARDIN, M
    BONNETERRE, J
    HECQUET, B
    PION, JM
    ADENIS, A
    HORNER, D
    DEMAILLE, A
    [J]. ANNALS OF ONCOLOGY, 1994, 5 (05) : 423 - 426
  • [10] Trastuzumab combined with chemotherapy for the treatment of HER2-positive metastatic breast cancer: Pivotal trial data
    Eiermann, W
    [J]. ANNALS OF ONCOLOGY, 2001, 12 : 57 - 62