Background
Chemotherapy-induced peripheral neuropathy (CIPN) is experienced by 37–84% of patients during and/or after end-of-treatment and often results in discontinuation of anti-neoplastic treatment and impairment of health-related quality of life. Cannabidiol (CBD) has shown preventive effects in CIPN animal models without compromising chemotherapy efficacy.

Methods
Patients with cancer referred for adjuvant treatment with capecitabine and oxaliplatin (CAPOX) or carboplatin and paclitaxel (Carbo-Tax) were recruited to participate in the CINCAN-2 study. CBD oil was self-administered two times daily (300 mg daily oral dose) for 8 days total at each cycle of chemotherapy, beginning 24 hours before start of chemotherapy. Patient reported outcomes (EORTC-CIPN20) were captured before start of chemotherapy and at follow-up until one year after end-of-chemotherapy. Vibration Perception Thresholds (VPTs) were collected at 32, 125 and 250Hz on patient dominant hand and at 8, 32, and 125Hz on the patient dominant foot. Controls were obtained from a similar cohort (CINCAN-1) receiving the same chemotherapy regimens, but no CBD.

Results
From March to December 2021, 54 out of 65 eligible patients were recruited. CINCAN-2 patients were significantly older (median age 64 vs 57 years, p=0.004) compared to the CINCAN-1 cohort. Patients treated with CBD showed significantly better VPT scores than patients not receiving CBD at 3, 6 and 12 months follow-up. The largest VTP difference was found in patients treated with Carbo-Tax and CBD at 32Hz in metatarsal V at 12 months with -1.86 Z-score, CI-95=[-3.16;-0.49] compared to patients who did not receive CBD. Patients treated with CAPOX and CBD scored significantly better in PRO scores at 3 and 6 month follow-up (-6.75 [-11.54;-1.98] and -9.25 [-13.91;-4.58] points respectively compared to patients treated with CAPOX only. No difference in PRO scores was observed for patients treated with Carbo-Tax. Patients receiving Carbo-Tax and CBD received significantly higher cumulative doses of paclitaxel (1737mg vs 1194mg, p=0.027) compared to patients receiving Carbo-Tax only.