PMID- 31231786 OWN - NLM STAT- MEDLINE DCOM- 20210303 LR - 20210303 IS - 1573-0646 (Electronic) IS - 0167-6997 (Linking) VI - 38 IP - 2 DP - 2020 Apr TI - A phase I dose-reduction study of apatinib combined with pemetrexed and carboplatin in untreated EGFR and ALK negative stage IV non-squamous NSCLC. PG - 478-484 LID - 10.1007/s10637-019-00811-6 [doi] AB - Objective Apatinib is an oral small molecule anti-angiogenic drug. This phase I study aimed to establish the feasible dose of apatinib in combination with pemetrexed plus carboplatin as first-line therapy for epidermal growth factor receptor (EGFR) and anaplasticlymphoma kinase (ALK) negative stage IV non-squamous non-small cell lung cancer (NSCLC). Methods Using a 3 + 3 dose-reduction design, patients received oral apatinib at four dose levels: 750 mg qd, 500 mg qd, 500 mg/day two weeks on/one week off schedule (500 mg schedule 2/1) or 250 mg qd. Pemetrexed (500 mg/m(2)) plus carboplatin (AUG = 5) was administered every three weeks. Maintenance therapy by apatinib or pemetrexed could be carried on until disease progression or unacceptable toxicity. The feasible dose was determined based on cycle 1 dose-limiting toxicities (DLT); other assessments included safety and antitumor activity according to response evaluation criteria in solid tumors. Result A total of twelve patients were enrolled and cycle 1 DLTs were observed in two patients at 750 mg qd dosage of apatinib (both Grade 3 hypertension), two patients at 500 mg qd (Grade 3 hypertension and Grade 3 hand-foot syndrome), and only one of six patients at 500 mg/day schedule 2/1 (Grade 3 hypertension). The most frequently drug-related adverse events (AEs) were hematological toxicity, hypertension, hand-foot syndrome, and hepatic transaminases elevation. Partial response was observed in four patients of eleven evaluable patients (objective response rate 36.4%), and six patients exhibited stable disease (disease control rate 90.9%). Conclusion In patients with advanced non-squamous NSCLC, the feasible dose of apatinib given with standard-dose pemetrexed and carboplatin was 500 mg/day schedule 2/1. The schedule was generally well tolerated and demonstrated promising clinical benefit in NSCLC. FAU - Huang, Meijuan AU - Huang M AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Gong, Youling AU - Gong Y AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Zhu, Jiang AU - Zhu J AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Qin, Yi AU - Qin Y AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Peng, Feng AU - Peng F AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Ren, Li AU - Ren L AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Ding, Zhenyu AU - Ding Z AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Liu, Yongmei AU - Liu Y AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Cai, Chengzhi AU - Cai C AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Wang, Yongsheng AU - Wang Y AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. FAU - Lu, You AU - Lu Y AUID- ORCID: 0000-0003-2133-6833 AD - Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China. radyoulu@hotmail.com. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190624 PL - United States TA - Invest New Drugs JT - Investigational new drugs JID - 8309330 RN - 0 (Antineoplastic Agents) RN - 0 (Pyridines) RN - 04Q9AIZ7NO (Pemetrexed) RN - 5S371K6132 (apatinib) RN - BG3F62OND5 (Carboplatin) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Aged MH - Anaplastic Lymphoma Kinase MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Carboplatin/*administration & dosage/adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology MH - ErbB Receptors MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/pathology MH - Male MH - Maximum Tolerated Dose MH - Neoplasm Staging MH - Pemetrexed/*administration & dosage/adverse effects MH - Pyridines/*administration & dosage/adverse effects MH - Treatment Outcome OTO - NOTNLM OT - Apatinib OT - Chemotherapy OT - NSCLC OT - Phase I EDAT- 2019/06/25 06:00 MHDA- 2021/03/04 06:00 CRDT- 2019/06/25 06:00 PHST- 2019/03/21 00:00 [received] PHST- 2019/06/06 00:00 [accepted] PHST- 2019/06/25 06:00 [pubmed] PHST- 2021/03/04 06:00 [medline] PHST- 2019/06/25 06:00 [entrez] AID - 10.1007/s10637-019-00811-6 [pii] AID - 10.1007/s10637-019-00811-6 [doi] PST - ppublish SO - Invest New Drugs. 2020 Apr;38(2):478-484. doi: 10.1007/s10637-019-00811-6. Epub 2019 Jun 24.