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Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer.
- Source :
-
BMC Cancer . 5/16/2019, Vol. 19 Issue 1, p1-10. 10p. 1 Diagram, 3 Charts, 2 Graphs. - Publication Year :
- 2019
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Abstract
- <bold>Background: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC.<bold>Trial Registration: </bold>ClinicalTrial.gov Identifier: NCT02969681 . [ABSTRACT FROM AUTHOR]
- Subjects :
- *VITAMIN C
*COLORECTAL cancer
*STOMACH cancer
*METASTASIS
*GASTROINTESTINAL agents
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 19
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- BMC Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 136502469
- Full Text :
- https://doi.org/10.1186/s12885-019-5696-z