A Phase I/II study of the combination of lapatinib and oral vinorelbine in HER2-positive metastatic breast cancer

Tom Wei-Wu Chen, Dah-Cherng Yeh, Tsu-Yi Chao, Ching-Hung Lin, Louis Wing-Cheong Chow, Dwan-Ying Chang, Yao-Yu Hsieh, Shu-Min Huang, Ann-Lii Cheng, Yen-Shen Lu

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4 Citations (Scopus)


Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment.

Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed.

Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years.

Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.

Original languageEnglish
Pages (from-to)242-247
Number of pages6
JournalJapanese Journal of Clinical Oncology
Issue number3
Publication statusPublished - Mar 1 2018


  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Breast Neoplasms/drug therapy
  • Demography
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lapatinib
  • Middle Aged
  • Neoplasm Metastasis
  • Quinazolines/adverse effects
  • Receptor, ErbB-2/metabolism
  • Treatment Outcome
  • Vinblastine/administration & dosage
  • Vinorelbine


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