Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer

BMC Cancer

Yu-Hong Li¹  Feng-Hua Wang¹  Feng Wang¹  Jia-Jia Hu¹  Chao Ren¹  Shuang-Zhen Chen¹  Si-Mei Shi¹  De-Shen Wang¹  Zi-Xian Wang¹  Ying Jin¹  Bing-Tian Bi¹  Zhi-Qiang Wang¹  Rui-Hua Xu¹  Zhi-Da Lv¹  Ming-Ming He¹  Su Li¹ 

[1] State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center;

关键词: Ascorbic acid;    Metastatic colorectal cancer;    Metastatic gastric cancer;    Recommended phase 2 dose;    chemotherapy;   

DOI  :  10.1186/s12885-019-5696-z

来源: DOAJ

【 摘 要 】

Abstract Background Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). Methods In the dose-escalation phase, patients received AA (0.2–1.5 g/kg, 3-h infusion, once daily, days 1–3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. Results Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1–3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3–4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. Conclusions The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. Trial registration ClinicalTrial.gov Identifier: NCT02969681.

【 授权许可】

Unknown