The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III-IV non-small cell lung cancer

• Published in: European journal of pharmaceutical sciences 2017-11, Vol.109, p.412-418
• Main Authors: Ou, Junwen, Zhu, Xinyu, Lu, Yimin, Zhao, Changlin, Zhang, Hongyu, Wang, Xiaopu, Gui, Xiaoshi, Wang, Junhua, Zhang, Xinting, Zhang, Tao, Pang, Clifford L.K.
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Aged; Ascorbic acid; Ascorbic Acid - administration & dosage; Ascorbic Acid - adverse effects; Ascorbic Acid - blood; Ascorbic Acid - pharmacokinetics; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Combined Modality Therapy; Electric Stimulation Therapy; Female; Humans; Hyperthermia, Induced; Lung Neoplasms - blood; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; mEHT; Middle Aged; Neoplasm Staging; Oxalic Acid - urine; Pharmacokinetics; Phase I clinical trial; Quality of Life; Single-Blind Method; Stage III-IV NSCLC
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2017.08.011

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. We carried out a clinical trial to evaluate the safety and pharmacokinetics of those methods in patients with stage III-IV non-small cell lung cancer (NSCLC). Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I study. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5g/kg AA infusions. Participants in the first group received intravenous AA (IVAA) when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. Pharmacokinetic profiles were obtained when they received solely IVAA and when IVAA in combination with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 4weeks. We found that fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAA-managed groups. IVAA synergy with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients. Pharmacokinetic plots of each treatment in the six groups by increasing dosage. Junwen Ou, Xinyu Zhu, et al. [Display omitted]