title: Efficacy, safety, pharmacokinetics and biomarker findings in patients with HER2-positive advanced or metastatic breast cancer treated with lapatinib in combination with capecitabine: results from 51 Japanese patients treated in a clinical study.
abstract: BACKGROUND
  The results from a phase III trial conducted outside of Japan demonstrated a significant improvement in time to progression (TTP) when lapatinib was combined with capecitabine compared with capecitabine alone in patients with HER2-positive advanced or metastatic breast cancer. In this clinical study of lapatinib in combination with capecitabine, efficacy, safety, pharmacokinetics (PK) and biomarkers were investigated in Japanese patients with HER2-positive advanced or metastatic breast cancer treated with prior trastuzumab.
  
  
  METHODS
  Eligible women received lapatinib 1250 mg once daily and capecitabine 1000 mg/m(2) twice daily on days 1 through 14 of a 21-day cycle. The primary endpoint was the clinical benefit rate (CBR: complete response, partial response or stable disease for at least 24 weeks).
  
  
  RESULTS
  Lapatinib in combination with capecitabine was well tolerated in the 51 patients enrolled in this study. CBR was 59 % (95 % CI 44.2, 72.4), and the median TTP in the Kaplan-Meier estimate was 36 weeks (95 % CI 27.1, 48.0). The majority of drug-related adverse events were mild to moderate (grade 1 or 2); the most common adverse events reported were palmar-plantar erythrodysesthesia syndrome (76 %), diarrhea (67 %) and stomatitis (41 %).
  
  
  CONCLUSIONS
  Lapatinib in combination with capecitabine in Japanese HER2-positive breast cancer patients was well tolerated. Overall, our findings on the efficacy, safety and PK were similar to those reported from the overseas studies.
authors.affiliation: Aichi Cancer Center Hospital, Breast Oncology, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan, hiwata@aichi-cc.jp.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mukai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Katsura
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Ellis
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gagnon
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000069287:Capecitabine / Q000008:administration & dosage / Q000493:pharmacokinetics; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D000069287:Capecitabine; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human