Meijuan Huang1, Yongmei Liu1, Min Yu1, Yanying Li1, Yan Zhang1, Jiang Zhu1, Li Li1, You Lu2,3. 1. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. 2. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. radyoulu@hotmail.com. 3. Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, 610041, China. radyoulu@hotmail.com.
Abstract
BACKGROUND: Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. METHODS: This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. CONCLUSION: The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.
BACKGROUND: Anlotinib hydrochloride is an oral small molecule inhibitor of multiple tyrosine kinases, and it has been approved as a third-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) in China. This dose-exploration study was designed to investigate the feasibility of anlotinib in combination with other chemotherapy regimens in patients with nonsquamous NSCLC. METHODS: This phase I study followed a 3 + 3 dose reduction design with three doses of anlotinib (12 mg, 10 mg, and 8 mg). Anlotinib was given at an initial dose of 12 mg with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC = 5) on 21-day cycles for 4 cycles. The primary goal of the study was to identify the maximum tolerated dose (MTD), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: A total of eight participants were enrolled. Dose-limiting toxicities (DLTs) were observed in two patients (pts) at anlotinib 12 mg (grade 3 hand-foot syndrome and grade 3 appetite loss). No DLTs occurred with 10 mg anlotinib, and the MTD was 10 mg. Among seven evaluable pts, four achieved a confirmed partial response (PR), and three had stable disease (SD). With a median follow-up of 10.05 months, the median PFS was 7.00 months (95% CI: 2.76 to NE). Grade 3 treatment-related adverse events (TRAEs) included appetite loss (n = 2), hypertension (n = 2), thrombocytopenia (n = 1), diarrhea (n = 1) and hand-foot syndrome (n = 1). No grade 4 or grade 5 TRAEs were observed during the treatment. CONCLUSION: The feasible dose of anlotinib in combination with platinum/pemetrexed-based chemotherapy as a first-line regimen was 10 mg, which was well tolerated and showed promising antitumor activity in advanced nonsquamous NSCLC.
Authors: S A Laurie; B J Solomon; L Seymour; P M Ellis; G D Goss; F A Shepherd; M J Boyer; A M Arnold; P Clingan; F Laberge; D Fenton; V Hirsh; M Zukin; M R Stockler; C W Lee; E X Chen; A Montenegro; K Ding; P A Bradbury Journal: Eur J Cancer Date: 2013-12-17 Impact factor: 9.162
Authors: Luis G Paz-Ares; Bonne Biesma; David Heigener; Joachim von Pawel; Timothy Eisen; Jaafar Bennouna; Li Zhang; Meilin Liao; Yan Sun; Steven Gans; Kostas Syrigos; Etienne Le Marie; Maya Gottfried; Johan Vansteenkiste; Vincente Alberola; Uwe Phillip Strauss; Elaine Montegriffo; Teng Jin Ong; Armando Santoro Journal: J Clin Oncol Date: 2012-07-30 Impact factor: 44.544
Authors: R Califano; N Tariq; S Compton; D A Fitzgerald; C A Harwood; R Lal; J Lester; J McPhelim; C Mulatero; S Subramanian; A Thomas; N Thatcher; M Nicolson Journal: Drugs Date: 2015-08 Impact factor: 9.546