PMID- 25967286 OWN - NLM STAT- MEDLINE DCOM- 20160823 LR - 20181202 IS - 1437-7772 (Electronic) IS - 1341-9625 (Print) IS - 1341-9625 (Linking) VI - 20 IP - 6 DP - 2015 Dec TI - 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. PG - 1102-9 LID - 10.1007/s10147-015-0832-5 [doi] AB - 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. FAU - Inoue, Kenichi AU - Inoue K AD - Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-adachi-gun, Saitama, 362-0806, Japan. ino@cancer-c.pref.saitama.jp. FAU - Kuroi, Katsumasa AU - Kuroi K AD - Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. FAU - Shimizu, Satoru AU - Shimizu S AD - Department of Breast Oncology and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. FAU - Rai, Yoshiaki AU - Rai Y AD - Hakuaikai Medical Corporation, Sagara Hospital, Kagoshima, Japan. FAU - Aogi, Kenjiro AU - Aogi K AD - Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. FAU - Masuda, Norikazu AU - Masuda N AD - Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan. FAU - Nakayama, Takahiro AU - Nakayama T AD - Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. AD - Department of Breast and Endocrine Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. FAU - Iwata, Hiroji AU - Iwata H AD - Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. FAU - Nishimura, Yuichiro AU - Nishimura Y AD - Development and Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan. FAU - Armour, Alison AU - Armour A AD - Research and Development, GlaxoSmithKline, Philadelphia, PA, USA. FAU - Sasaki, Yasutsuna AU - Sasaki Y AD - Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan. AD - Division of Medical Oncology, Department of Medicine, Showa University Hospital, Tokyo, Japan. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150513 PL - Japan TA - Int J Clin Oncol JT - International journal of clinical oncology JID - 9616295 RN - 0 (Hemoglobins) RN - 0 (Quinazolines) RN - 0VUA21238F (Lapatinib) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Aged MH - Alopecia/chemically induced MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/pharmacokinetics/*therapeutic use MH - Area Under Curve MH - Breast Neoplasms/chemistry/*drug therapy/pathology MH - Diarrhea/chemically induced MH - Female MH - Hemoglobins/metabolism MH - Humans MH - Japan MH - Lapatinib MH - Middle Aged MH - Neoplasm Metastasis MH - Paclitaxel/administration & dosage/adverse effects/blood/pharmacokinetics MH - Quinazolines/administration & dosage/adverse effects/blood/pharmacokinetics MH - Receptor, ErbB-2/*analysis/antagonists & inhibitors MH - Survival Rate PMC - PMC4666271 OTO - NOTNLM OT - HER2 OT - Lapatinib OT - Metastatic breast cancer OT - Paclitaxel EDAT- 2015/05/15 06:00 MHDA- 2016/08/24 06:00 PMCR- 2015/05/13 CRDT- 2015/05/14 06:00 PHST- 2015/01/23 00:00 [received] PHST- 2015/04/14 00:00 [accepted] PHST- 2015/05/14 06:00 [entrez] PHST- 2015/05/15 06:00 [pubmed] PHST- 2016/08/24 06:00 [medline] PHST- 2015/05/13 00:00 [pmc-release] AID - 10.1007/s10147-015-0832-5 [pii] AID - 832 [pii] AID - 10.1007/s10147-015-0832-5 [doi] PST - ppublish SO - Int J Clin Oncol. 2015 Dec;20(6):1102-9. doi: 10.1007/s10147-015-0832-5. Epub 2015 May 13.