Drinking cola appeared to improve the bioavailability of erlotinib during treatment with a proton pump inhibitor in patients with non–small cell lung cancer, according to results of a randomized, pharmacokinetic study.
The lung cancer drug erlotinib (Tarceva, Genentech) relies on the pH level of the stomach for effective delivery. Most patients with NSCLC also have to take a proton pump inhibitor to reduce their acid level; however, these inhibitors increase stomach pH levels and cause a drug–drug interaction with erlotinib, reducing its absorption.
Roelof W.F. van Leeuwen, PharmD
“It has been known for some time that stomach protectors can significantly reduce blood levels of erlotinib,” Roelof W.F. van Leeuwen, PharmD, researcher at Erasmus Medical Center Cancer Institute, told HemOnc Today. “This puts the treating physician in a dilemma — without stomach protectors, absorption of erlotinib is good, but to stop taking stomach protectors can cause harmful stomach problems because of co-medication.”
Previous data have indicated that the proton pump inhibitor omeprazole reduced the area under the curve (AUC) of erlotinib by 46% and the maximum serum concentration in the blood (Cmax) by 61%.
“The use of stomach protectors results in the drugs not being absorbed effectively enough, and may inhibit slowing down the cancer’s growth,” van Leeuwen said. “In this study we were really looking for a simple and practical solution for this everyday problem.”
Van Leeuwen and colleagues conducted a cross-over study of 28 patients with NSCLC between March 2014 and June 2015.
Patients received erlotinib at any dose for 2 weeks alone (group A, n = 14) or with 40 mg of the proton pump inhibitor esomeprazole (Nexium, AstraZeneca; group B, n = 14).
Within group A and B, the researchers divided patients into groups of seven and assigned them to sequence A — erlotinib with 250 mL water for 7 days followed by 250 mL Coca-Cola Classic for 7 days — or sequence B, which started with Coca-Cola first.
The researchers found that in the patients treated with esomeprazole, the mean AUC0-12h of erlotinib increased 39% (range, 12-136; P = .004) and the Cmax increased 42% (range, –4 to 199; P = .019) with Coca-Cola vs. water. However, for the patients not treated with esomeprazole, the mean AUC0-12h of erlotinib only increased 9% (range, –10 to 30; P = .03) and the Cmax remained the same (0%; range, –19 to 18) with Coca-Cola vs. water.
“The most surprising finding was that the answer to all our problems appeared to be within something as simple as taking the pill with a glass of Coke,” van Leeuwen said. “When taken with a glass of Coke (instead of water), the stomach is temporarily acidified and, as a result, erlotinib blood levels in patients who were also taking stomach protectors increased by an average of almost 40%. In some patients this increase was even by more than 100%.”
The researchers indicated that a limitation of their study was that intragastric pH was not measured. Additionally, the study was not designed to examine the long-term effects of Coca-Cola coadministration with erlotinib on the outcomes of the treatment.
“Other acidic beverages [like] orange juice [or] other carbonated drinks may have similar effects as cola and should be explored in future trials,” the researchers wrote. – by Anthony SanFilippo
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Roelof W.F. van Leeuwen, PharmD, can be reached at firstname.lastname@example.org.
Disclosure: van Leeuwen reports research funding from Roche. Please see the full study for a list of all other researchers’ relevant financial disclosures.