Smoking Cessation Regimens: Does Dose of Therapy Matter?

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Altering or increasing the dosages of smoking cessation regimens may help patients quit smoking, according to a recent study published by Cinciripini et al in JAMA. The findings indicated that the smoking cessation drug varenicline may be more effective than combined nicotine replacement therapy such as patches or lozenges in this patient population.


Tobacco use remains the leading preventable cause of mortality and disease in the United States. Currently, more than 16 million U.S. individuals suffer from at least one smoking-related disease—including cancer—and about 480,000 U.S. individuals die of tobacco-related diseases each year. Quitting smoking can improve the rate of survival by 30% to 40% among patients with cancer who smoke.

The average smoker may make several attempts to quit before successfully overcoming the addiction.

Study Methods and Results

In the recent study, the researchers randomly assigned 490 smokers to receive either 2 mg varenicline or combined nicotine replacement therapy (a 21-mg patch plus a 2-mg lozenge) for 6 weeks. After the first phase of the study, the participants who were unable to quit smoking were again randomly assigned to continue with their cessation regimens at the same doses, switch between varenicline and combined nicotine replacement therapy regimens, or increase their drug dose to 3 mg for the varenicline group or a 42-mg patch plus a 2-mg lozenge for the combined nicotine replacement therapy group for an additional 6 weeks. The study was conducted from June 2015 to October 2019.

Among the participants who received varenicline and had their doses increased during the rerandomization phase of the study, 20% were still abstaining from smoking at 6 weeks. The abstinence rate was 14% among those who switched from combined nicotine replacement therapy to varenicline or who had their combined nicotine replacement therapy doses increased. However, the participants who initially received varenicline and switched to combined nicotine replacement therapy experienced a 0% abstinence rate. After a follow-up of 6 months, only those who had their doses increased remained continuously abstinent.

The researchers revealed that smokers who failed to quit with varenicline in the first phase were seven times more likely to quit by the end of the second phase if varenicline doses were increased. There also was a nearly twofold increase in the number of smokers who successfully quit if they switched from the combined nicotine replacement therapy regimen to varenicline.


“These data indicate that sticking to the same medication isn’t effective for smokers who are unable to quit in the first 6 weeks of treatment," underscored lead study author Paul Cinciripini, PhD, Chair of Behavioral Science at The University of Texas MD Anderson Cancer Center. “Our study should encourage [physicians] to check in on patients early in their cessation journey and, if patients are struggling, to try a new approach such as increasing medication dosage,” he concluded.

In a larger ongoing trial, the researchers are examining whether several different drug combinations may be effective as alternative therapy in smokers unable to quit on their initial doses of varenicline or combined nicotine replacement therapy.

Disclosure: The research in this study was supported by the Cancer Prevention and Research Institute of Texas, The University of Texas MD Anderson Cancer Center’s Lung Cancer Moon Shot, the National Cancer Institute, and the State of Texas Permanent Health Funds. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.