title: Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients.
  
  
  METHODS
  In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles.
  
  
  RESULTS
  The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9).
  
  
  CONCLUSIONS
  The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.
authors.affiliation: Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan. ino@cancer-c.pref.saitama.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kuroi
authors.affiliation: Department of Breast Oncology and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Hakuaikai Medical Corporation, Sagara Hospital, Kagoshima, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Rai
authors.affiliation: Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.affiliation: Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Development and Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Research and Development, GlaxoSmithKline, Philadelphia, PA, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Armour
authors.affiliation: Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan.|Division of Medical Oncology, Department of Medicine, Showa University Hospital, Tokyo, Japan.
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007564:Japan; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors; D015996:Survival Rate
chemical_list: D006454:Hemoglobins; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2; Lapatinib; Metastatic breast cancer; Paclitaxel