A phase I evaluation of the effect of curcumin on dose‐limiting toxicity and pharmacokinetics of irinotecan in participants with solid tumors. Issue 5 (26th February 2022)

• Record Type: Journal Article
• Authors: Gbolahan, Olumide B.; O'Neil, Bert H.; McRee, Autumn J.; Sanoff, Hanna K.; Fallon, John K.; Smith, Philip C.; Ivanova, Anastasia; Moore, Dominic T.; Dumond, Julie; Asher, Gary N.
• Is Part Of: Clinical and translational science. Volume 15:Issue 5(2022)
• Page Start: 1304
• Page End: 1315
• Publication Date: 2022-02-26
• Subjects: Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; 616.027
• DOI: 10.1111/cts.13250
• Languages: English
• ISSNs: 1752-8054

Abstract

Abstract: Curcumin inhibits UDP‐glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m 2 of i.v. infusion irinotecan on days 1 and 15 of a 28‐day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN‐38 and SN‐38G. Irinotecan, SN‐38, and SN‐38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration‐time curves from 0 to 6 h (AUC0‐6h ). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well‐tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan‐associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5–39%), median progression free survival and overall survival ( n = 23) were 4 months (95% CI: 2.9–8.9 months) and 8.4 months (95% CI: 3.7 – not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.