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From OncoLog, May 2013, Vol. 58, No. 5

Graphic: In Brief

Beta-Blocker Use Associated With Higher Survival Rates in Lung Cancer Patients Receiving Radiation Therapy

Using beta-adrenergic receptor antagonists (beta-blockers) prolongs survival in patients with non–small cell lung cancer (NSCLC) undergoing definitive radiation therapy, findings from a study at The University of Texas MD Anderson Cancer Center suggest.

The analysis, led by Daniel Gomez, M.D., an assistant professor in the Department of Radiation Oncology, found that the incidental use of beta-blockers in this population was associated with longer distant metastasis–free, disease-free, and overall survival.

Of the 722 patients included in the retrospective study, 155 had received beta-blocker treatment during radiation therapy. About two-thirds of those patients received beta-blockers to treat hypertension, and most of the remaining third received them to treat coronary heart disease.

A univariate analysis comparing outcomes for patients who received beta-blockers with those who did not revealed that the use of beta-blockers was associated with longer distant metastasis–free, disease-free, and overall survival. After adjustment for age, Karnofsky performance score, disease stage, tumor histology, use of concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease, and aspirin use, a multivariate analysis revealed that the use of beta-blockers was still associated with longer distant metastasis–free, disease-free, and overall survival.

Several factors other than beta-blocker use also were significantly associated with survival. Concurrent chemotherapy was associated with longer overall survival; age younger than 65 years was associated with longer disease-free survival; a Karnofsky score greater than 80 was associated with longer distant metastasis–free survival, disease-free survival, and overall survival; and stage III disease was associated with shorter distant metastasis–free survival, disease-free survival, and overall survival.

The study was reported in Annals of Oncology in January. Dr. Gomez and his co-authors recommended prospective trials to determine whether the length and timing of beta-blocker use influence survival for cancer patients.

Selumetinib Shows Promise for Patients With Recurrent Low-Grade Ovarian Cancer

Selumetinib, a MEK1/2 inhibitor, benefits some patients with recurrent low-grade serous ovarian cancer, according to the results of a recent phase II clinical trial.

The open-label, single-arm study—the first to evaluate targeted therapy for low-grade serous ovarian cancer—enrolled 52 patients with recurrent disease who had undergone at least one prior therapy. Patients were given 50 mg of oral selumetinib twice daily for a median of 4.5 4-week cycles; individual patients’ doses were adjusted on the basis of the hematological, dermatological, and/or gastrointestinal adverse events they experienced.

Selumetinib elicited a complete or partial response in 8 patients (15%) and stabilized disease for at least 6 months in 34 patients (65%). The median progression-free survival duration was 11 months, and the 2-year overall survival rate was 55%. There were no treatment-related deaths.

“These are remarkably encouraging results for what can ultimately be a devastating disease,” said David Gershenson, M.D., a professor in the Department of Gynecological Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center and the senior author of the study’s report.

The grade 4 adverse events experienced in the study were pain (1 patient) and cardiac and pulmonary events (1 patient each). Grade 3 adverse events included cardiotoxicity, gastrointestinal events, pain, fatigue, and anemia. Owing to these adverse events, the selumetinib dose was reduced in 22 patients, and 13 patients ultimately left the study.

Although low-grade serous ovarian cancer is less aggressive than its high-grade counterpart, it is extremely difficult to treat if initial therapy fails—and the cancer will persist or recur in more than 80% of patients. Recurrent or relapsed low-grade serous ovarian cancer is less susceptible to standard therapies than is high-grade disease, and response rates for recurrent or relapsed low-grade disease are usually below 10%.

“After surgery with or without pre-surgical chemotherapy, when low-grade serous ovarian cancer persists or returns, chemotherapy and hormonal therapy are relatively ineffective,” Dr. Gershenson said.

Selumetinib inhibits MEK1/2, a critical molecule in the MAPK signaling pathway, which includes BRAF and KRAS. BRAF and KRAS mutations are common in low-grade serous ovarian cancers. In the study, 14 patients had KRAS mutations, and 2 had BRAF mutations; but a patient’s having either mutation was not connected to her selumetinib response.

The study was conducted by the National Cancer Institute’s Gynecologic Oncology Group, and the report was published in the February edition of The Lancet Oncology.

Varenicline Improves Smokers’ Chances of Stopping Smoking

Smokers in a smoking cessation study who took varenicline had a higher probability of quitting smoking and a better overall cessation experience than did those who took bupropion or placebo, a team of researchers at The University of Texas MD Anderson Cancer Center has reported.

The team, led by Paul Cinciripini, Ph.D., a professor in the Department of Behavioral Science and the director of the Tobacco Treatment Program at MD Anderson, investigated the relative efficacy of varenicline and bupropion, two popular smoking cessation drugs, in nearly 300 people who were trying to quit smoking. Participants were randomly assigned to receive varenicline, bupropion, or placebo; they also underwent extensive smoking cessation counseling. Participants were assessed for nicotine withdrawal and emotional functioning every week during treatment.

The researchers found that, compared with placebo, only varenicline significantly improved smoking abstinence rates by all measures at all time points—a finding that is consistent with the results of phase III clinical trials of varenicline. Compared with placebo, both varenicline and bupropion reduced participants’ nicotine cravings, but people taking varenicline had less intense cravings for nicotine, even if they did not quit smoking.

“When smokers try to quit, many are likely to experience a range of nicotine withdrawal symptoms—including negative mood, difficulty concentrating, irritability, and even depressive symptoms—making quitting difficult and increasing the chances of relapse,” Dr. Cinciripini said. “Our findings suggest that smokers trying to quit will have a better experience with varenicline as opposed to trying to quit on their own or taking bupropion.”

Dr. Cinciripini and his colleagues also found that regardless of whether varenicline or bupropion was received, people who were able to abstain from smoking not only showed lower negative affect, less anxiety, and less sadness but also showed higher positive affect than those who were not able to abstain from smoking.

“This is a very interesting finding in that it suggests smoking itself may not be a very good antidepressant,” Dr. Cinciripini said. “It also suggests that those who are able to abstain from smoking will ultimately feel better than those who continue to smoke.”

The study was published online by JAMA Psychiatry in March.

For more information, talk to your physician, visit, or call askMDAnderson at 877-632-6789.

Other articles in OncoLog, May 2013 issue:


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