Oral cannabidiol for prevention of acute and transient chemotherapy-induced peripheral neuropathy.

PURPOSE: To assess the safety, dosing, and preventive effects of cannabidiol (CBD) on chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving oxaliplatin- or paclitaxel-based chemotherapy. METHODS: Patients with cancer scheduled to undergo treatment with carboplatin and paclitaxel (Carbo-Tax) or capecitabine and oxaliplatin (CAPOX) received 150 mg CBD oil twice daily (300 mg/daily) for 8 days beginning 1 day before initiation of chemotherapy. Ten CIPN-specific patient-reported outcome (PRO) measures were captured at baseline and each day after the first cycle of chemotherapy for 8 days. Multi-frequency vibrometry (MF-V) was captured at baseline and day 4 ± 1 after initiation of chemotherapy. Controls were obtained from a similar patient cohort that did not receive CBD. Adverse events were captured using the CTCAE ver. 4.03. RESULTS: From March to December 2021, 54 patients were recruited. CBD-treated patients were significantly older (p = 0.013/0.037, CAPOX/Carbo-Tax) compared to controls. Patients receiving CBD and CAPOX or Carbo-Tax showed significantly lower (better) change in Z-scores in high-frequency MF-V (125 and 250 Hz) compared to controls. This difference was most pronounced for patients receiving Carbo-Tax (- 1.76, CI-95 = [- 2.52; - 1.02] at 250 Hz). CAPOX patients treated with CBD had significantly lower peak baseline-adjusted difference in three PRO items on cold sensitivity to touch, discomfort swallowing cold liquids, and throat discomfort (- 2.08, - 2.06, and - 1.81, CI-95 = [- 3.89; - 0.12], NRS 0-10). No significant differences in PRO items were found for patients receiving Carbo-Tax. Possible side effects included stomach pain (grades 1-2) for patients receiving CAPOX. CONCLUSION: CBD attenuated early symptoms of CIPN with no major safety concerns. Long-term follow-up is ongoing. Results should be confirmed in a larger, randomized study. TRIAL REGISTRATION NUMBER: NCT 04,167,319 (U.S National Library of Medicine; ClinicalTrials.gov). Date of registration: November 18, 2019.

[Cardiotoxicity induced by 5-fluorouracil or capecitabine]. / Hjertepåvirkning fra 5-fluorouracil og capecitabin.

5-fluorouracil and capecitabine have significant antineoplastic activity towards various solid tumors. Cardiotoxicity causing angina, arrhythmia and infarction are serious adverse events associated with these agents. The pathogenesis is discussed and symptoms of cardiotoxicity, intervention with nitroglycerine and risk factors as cardiac comorbidity are described. Following cardiotoxicity, lack of alternative active agents may provide grounds to rechallenge with 5-FU. In this situation, dose-modified 5-FU-based chemotherapy supported by medical antiangina prevention is feasible.