A randomized phase II trial of best supportive care with or without hyperthermia and vitamin C for heavily pretreated, advanced, refractory non-small-cell lung cancer

Overall Survival Time

Overall Survival Time

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Summary

Our previous study indicated that intravenous vitamin C (IVC) treatment concurrent with modulated electrohyperthermia (mEHT) was safe and improved the quality of life (QoL) of non-small-cell lung cancer (NSCLC) patients. Overall, IVC and mEHT may have the ability to improve the prognosis of patients with advanced NSCLC.

Patients characteristics

97 patients were adults (>18 years ≤70 years old) who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; who had a histologically proven diagnosis of primary NSCLC, stage IIIb or IV; who were not curable with surgery or showed radiographically confirmed PD during previous radiotherapy and/ or four to six cycles of platinum-based chemotherapy; who had failed to respond to targeted therapy or immunotherapy or were intolerant of their latest anticancer therapy regimen; and who showed at least one measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Methodology

The applicator used was 7.1 2dm . The applied energy range in one session was between 486 kJ and 540 kJ. The patients were placed lying in the prone position, and the treatment covered the complete lung (30 cm diameter circle). The temperature of the treatment area was in the range of 40–42oC, calculated indirectly by the treatment device. BSC focuses on helping patients obtain relief from symptoms such as nausea, pain, fatigue or shortness of breath.

Treatment

97 patients were randomly assigned to receive IVC + mEHT + BSC (n = 49) or BSC alone (n = 48). BSC included multi-disciplinary care, BSC documentation, symptom assessment and symptom management.
In the active arm, patients received IVC 1 g/kg d three times a week for 25 treatments in total. Each milliliter of vitamin C injection contained 3 g of sodium ascorbate and water for injection, with the pH adjusted to 6.5–8.0 with
sodium bicarbonate. Vitamin C was infused for 120 min. We used the mEHT method for HT treatment with the EHY2000+ device.
The treatment regimen of mEHT was 60 min/session; the power of mEHT was gradually increased
from 135 W to 150 W depending on the patient’s actual tolerance.

Results

Efficacy
The log-rank test and Kaplan–Meier plots of OS and PFS showed highly significant differences (P < 0.05) between the active and control arms. The median OS was 9.4 months for the active arm and 5.6 months for the control arm (P < 0.0001). The median PFS was 3.0 months for the active arm and 1.85 months for the control arm (P < 0.0001). Neither OS nor PFS were affected by the pathological type of carcinoma.By using the RECIST 1.1 criteria, 5 of 49 (10.2%) subjects in the active arm had PR, while no PR was observed in the control arm; 16 of 49 (32.7%) subjects in the active arm and 8 of 48 (16.7%) subjects in the control arm had SD; and 28 of 49 (57.1%) subjects in the active arm and 40 of 48 (83.3%) subjects in the control arm had PD. No CR was observed in both two arms. The 3-month disease control rate (DCR) was 42.9% in the treatment arm and 16.7% in the control arm. Adverse effects and toxicity
The overall adverse effects of IVC and mEHT were marginal. Thirst was the major symptom during all of the treatments. Adverse effects were measured in 22/49 (44.9%) of subjects in the active arm. Symptoms disappeared when the treatments ended, except for one patient who experienced severe diarrhea. This patient was withdrawn from the study at the stage when he ended the second combined treatment. Acute toxicity was not observed in other patients at any stage of treatment. No significant differences were registered in full blood count or biochemical and hematologic profiles before and after the treatment.
Quality of life
The QLQ-C30 scores were recorded over the full cycle of the study. The average scores for the functioning scales increased continuously, so QoL improved.In comparison, the differences in physical, emotional and global improvement after 9 weeks of therapy between the control and the active arms were significant. The psychometric parameters (symptoms) decreased gradually in the active arm of the study, despite the advanced NSCLC and the short (nine week) period of study. The symptoms in the control arm became stronger with time.

Conclusion

In summary, IVC + mEHT is well tolerated, significantly improves QoL, prolongs PFS and OS, and moderates’ cancer-related inflammation, so it is a feasible treatment in advanced NSCLC.

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Scientific article publishing date : 3/17/2020

Immucura identifier BSC21_172EN

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