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

Autor: Ming-Ming He, Rui-Hua Xu, S. Chen, Zi-Xian Wang, Si-Mei Shi, Feng Wang, De Shen Wang, Ying Jin, Bing-Tian Bi, Jia-Jia Hu, Chao Ren, Su Li, Fenghua Wang, Zhi-Da Lv, Yu Hong Li, Zhi Qiang Wang
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
Cancer Research
medicine.medical_specialty
Maximum Tolerated Dose
Colorectal cancer
medicine.medical_treatment
Ascorbic Acid
Neutropenia
lcsh:RC254-282
Gastroenterology
Recommended phase 2 dose
chemotherapy
03 medical and health sciences
0302 clinical medicine
Asian People
Stomach Neoplasms
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Genetics
medicine
Humans
Neoplasm Metastasis
Stomach cancer
Aged
Chemotherapy
Leukopenia
Metastatic colorectal cancer
business.industry
Cancer
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Ascorbic acid
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
FOLFIRI
Female
medicine.symptom
Colorectal Neoplasms
business
Metastatic gastric cancer
Research Article
Zdroj: BMC Cancer
BMC Cancer, Vol 19, Iss 1, Pp 1-10 (2019)
ISSN: 1471-2407
DOI: 10.1186/s12885-019-5696-z
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12885-019-5696-z) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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