PMID- 35840914 OWN - NLM STAT- MEDLINE DCOM- 20220719 LR - 20220720 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 22 IP - 1 DP - 2022 Jul 15 TI - Phase 1 trial of apatinib combined with intensity-modulated radiotherapy in unresectable hepatocellular carcinoma. PG - 771 LID - 10.1186/s12885-022-09819-3 [doi] LID - 771 AB - BACKGROUND: To investigate the maximum tolerated dose (MTD) of apatinib delivered during and after intensity-modulated radiotherapy (IMRT) for unresectable hepatocellular carcinoma (HCC). METHODS: Patients with unresectable HCC who were not eligible for radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), or residual/ recurrent after the prior local treatment were enrolled. Patients were scheduled to be treated with IMRT at 50-60 Gy/25-30 fractions. Oral apatinib tablets were administered concurrently with IMRT and continued thereafter. We used a 3 + 3 dose-escalation design, with three dose levels of apatinib (250, 500, and 750 mg). Grade 3 or more severe adverse events (AEs) were defined as dose-limiting toxicities (DLTs). The treatment response was calculated using the Modified Response Evaluation Criteria in Solid Tumours. RESULTS: Nine patients with Barcelona Clinic Liver Cancer Stage C were included. One patient withdrew from the apatinib 250 mg group and another patient was added. No DLTs occurred in the apatinib 250 mg group. Five patients were included in the apatinib 500 mg group, and 2 cases of DLT (grade 3 leukopenia) were found among them. Dose escalation was terminated and the MTD was determined to be 250 mg. Common grade 1-2 AEs included fatigue, hypertension, dizziness, bone marrow suppression, and hyperbilirubinemia. The median follow-up time for all patients was 16.0 months. Three patients achieved complete response and another three achieved partial response. The objective response rate was 6/9 (66.7%), and the disease control rate was 9/9 (100%). Three patients relapsed out of the radiation field. The median progression-free survival was 17.0 months, and the median overall survival was 16.7 months. CONCLUSIONS: When combined with IMRT, apatinib 250 mg daily was recommended for a phase 2 study of unresectable HCC. The antitumor activity of the combination treatment was encouraging. The safety and efficacy of apatinib combined with IMRT for unresectable HCC should be further investigated in future studies. TRIAL REGISTRATION: Registration No. ChiCTR1800018309 . Registered 11 September 2018. Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=30461 . CI - (c) 2022. The Author(s). FAU - Wang, Hongzhi AU - Wang H AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Zhu, Xianggao AU - Zhu X AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Zhao, Yuting AU - Zhao Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Dong, Dezuo AU - Dong D AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Li, Lijuan AU - Li L AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Cai, Yong AU - Cai Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Li, Yongheng AU - Li Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. FAU - Wang, Weihu AU - Wang W AUID- ORCID: 0000-0003-4969-398X AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, No. 52 Fu-cheng Road, Haidian District, Beijing, 100142, People's Republic of China. wangweihu88@163.com. LA - eng GR - 82073333/national natural science foundation of china/ GR - Z181100001718192/beijing municipal science & technology commission/ GR - 7182028/beijing natural science foundation/ GR - XMLX201842/clinical technology innovation project of beijing hospital authority/ PT - Clinical Trial, Phase I PT - Journal Article DEP - 20220715 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Pyridines) RN - 5S371K6132 (apatinib) SB - IM MH - *Carcinoma, Hepatocellular/drug therapy/radiotherapy MH - Combined Modality Therapy/adverse effects MH - Humans MH - *Liver Neoplasms/drug therapy/radiotherapy MH - Pyridines/therapeutic use MH - Radiotherapy, Intensity-Modulated PMC - PMC9287866 OTO - NOTNLM OT - Apatinib OT - Intensity-modulated radiotherapy OT - Unresectable hepatocellular carcinoma OT - maximum tolerated dose COIS- All authors have read the journal's policy and declare no conflicts of interest. EDAT- 2022/07/16 06:00 MHDA- 2022/07/20 06:00 PMCR- 2022/07/15 CRDT- 2022/07/15 23:39 PHST- 2021/08/04 00:00 [received] PHST- 2022/06/24 00:00 [accepted] PHST- 2022/07/15 23:39 [entrez] PHST- 2022/07/16 06:00 [pubmed] PHST- 2022/07/20 06:00 [medline] PHST- 2022/07/15 00:00 [pmc-release] AID - 10.1186/s12885-022-09819-3 [pii] AID - 9819 [pii] AID - 10.1186/s12885-022-09819-3 [doi] PST - epublish SO - BMC Cancer. 2022 Jul 15;22(1):771. doi: 10.1186/s12885-022-09819-3.