P1.01-071 High Dose IVAA Synergy with mEHT in Patients with Stage III-IV NSCLC: A Phase I Study

Abstract

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no sufficient data in safety, quality of life and clinical response of the above treatments in patients with stage III-IV Non-Small Cell Lung Cancer (NSCLC).We designed a Phase I trial to provide the evidence. 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 -II study. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5g/kgAA infusions. Pharmacokinetic profiles were obtained when they received solely IVAA at concentrations of 1g/kg, 1.2g/kg, and 1.5g/kg, and when IVAA in combination with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 8 weeks. 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. DLT was defined as any reversible grade ≥3 adverse events, whether hematological or non-hematological. CT enhanced scan were collected from the patients before the treatment and one month after the treatment finished. Fasting plasma AA levels were significantly correlated with stage of the disease. The overall toxicity was marginal. Thirstiness was the major symptom during all of the treatments. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IV AA-managed groups. The average scores for the functioning scales continuously increased and the symptoms gradually decrease over the full cycle of the study. By using RECIST 1.1 criteria, two of four subjects diagnosed with lung squamous cell carcinoma had partial response (PR), two of four had stable disease(SD). Two of ten patients diagnosed with lung adenocarcinoma had had PR, three of ten had SD, five of ten had progressive disease. IVAA synergies with simultaneous mEHT were safe and can be well tolerated in patients. Patients diagnosed with squamous cell lung cancer were sensitive to the above two treatments. There’s a need for a phase II study with advanced NSCLC patients administering mEHT simultaneously with IVAA to assess for the efficacy and progression free survival time.