Missed a Highlight? The NCI Cancer Bulletin Archive allows you to search every issue of this online publication since January 2004. That's over 100 weeks' worth of articles on a variety of cancer research topics and updates.

Varenicline Helps More Smokers Quit for Longer with Fewer Side Effects

Several articles published in the July 5 Journal of the American Medical Association discuss the safety, efficacy, and side effects of a smoking cessation drug, varenicline (Chantix), which was approved by the FDA in May of this year. The related studies were supported by the drug's manufacturer, Pfizer, and conducted by the Varenicline Phase 3 Study Group.

Dr. David Gonzales and colleagues tested the efficacy of 1 mg of varenicline given twice a day for 12 weeks against 150 mg of the sustained-release antidepressant bupropion - also a smoking cessation aid - as well as a placebo. Of the 1,025 smokers who participated, 44 percent who received varenicline were able to quit smoking between weeks 9 and 12, while 29.5 percent quit with buproprion and 17.7 percent quit with placebo. After 52 weeks, abstinence dropped to 21.9 percent for varenicline, 16.1 percent for bupropion, and 8.4 percent for placebo. The test group reported nausea and insomnia, but generally had fewer side effects than those who took bupropion. These results were mirrored by Dr. Douglas E. Jorenby and colleagues, who tested a similar protocol in 1,027 smokers.

A third study, by Dr. Serena Tonstad and colleagues, showed that an additional 12 weeks of treatment with varenicline significantly improved continuous abstinence up to 52 weeks after the study began: 43.6 percent remained smoke free between weeks 13 and 52, compared with 36.9 percent who received a placebo throughout the same period.

In an editorial, Drs. Robert C. Klesges, Karen C. Johnson, and Grant Somes of the University of Tennessee Health Science Center and St. Jude Children's Research Hospital acknowledged that varenicline is effective for smoking cessation, but warned that high dropout rates in the nonvarenicline study groups may have skewed results in favor of the drug. Noting that the majority of participants in the three related studies were unable to quit smoking, even with pharmacologic aids, they wrote, "Patients currently cannot and probably never will simply be able to 'take a pill' that will make them stop smoking. Smokers must want to stop smoking and must be willing to work hard to achieve [that goal]."

Survivors of Childhood Cancer Risk Premature Menopause

A woman who survives cancer as a child has a greatly increased risk of experiencing menopause before she reaches age 40. If this occurs, her risk for osteoporosis, cardiac disease, and psychosexual dysfunction increases.

Researchers working with the Childhood Cancer Survivors Study (CCSS), a retrospective longitudinal cohort study of more than 20,000 childhood cancer survivors diagnosed between 1970 and 1986, found that survivors had nonsurgical premature menopause at a rate 13 times greater than the control group. The affected women were older at time of assessment, more likely to have had Hodgkin lymphoma, less likely to have had leukemia, and had greater ovarian exposure to radiation and/or alkylating chemotherapy agents.

Dr. Charles A. Sklar of Memorial Sloan-Kettering Cancer Center and colleagues identified 2,819 CCSS subjects who were menstruating more than 5 years after their cancer diagnosis; controls were selected from among survivors' siblings, not always from the same families - in this case 1,065 age-matched women with normal menstrual patterns.

In an accompanying editorial in the July 5 Journal of the National Cancer Institute (JNCI), Drs. Wendy Y. Chen and JoAnn E. Manson of Harvard Medical School wrote, "the health consequences of premature menopause are still poorly understood," noting that some of them are controversial, and not all are negative: such women have a lower risk of breast and ovarian cancer. Nonetheless, this study helps clinicians identify women for whom counseling, prevention, screening, and treatment strategies should be considered.

Biomarker IMP3 Predicts Kidney Cancer Metastasis and Survival

Researchers found that expression of the IMP3 protein by renal carcinoma tumors indicates a high risk of metastasis, which is the main cause of death in this most common type of kidney cancer, according to results published in the July issue of Lancet Oncology.

Based on a study of 501 primary and metastatic renal-cell tumors, IMP3 expression was greatly increased not only in metastatic tumors but also in a subset of primary tumors that were likely to subsequently develop metastases. "Patients with IMP3-positive primary tumors were almost six times more likely to subsequently develop metastasis than were those with IMP3-negative tumors," explain the investigators, led by Dr. Zhong Jiang of the University of Massachusetts Medical Center.

This high predictive value makes IMP3 potentially useful as "an independent prognostic marker that can be used at initial diagnosis of renal-cell carcinoma to identify patients who have a high potential to develop metastasis and who might benefit from early systemic treatment," the researchers suggest.

The metastatic potential of localized kidney tumors is difficult to predict, but about 20 percent of patients with localized tumors develop metastasis, and the median survival for those with metastatic disease is roughly 13 months. "Therefore, biomarkers that can accurately distinguish localized tumors with a high probability of metastasis from those that will remain indolent are needed," the scientists add.

IMP3 immunohistochemical staining "is a simple, inexpensive, and reliable assay" and "can be used at initial diagnosis - the best time for considering early systemic treatment," they recommend.

Chornobyl Nuclear Accident's Impact on Thyroid Cancer Risks

Little has been known about the carcinogenic effects of radioactive iodines on children. The first cohort study on the impact of the 1986 Chornobyl Reactor accident shows that the risk of thyroid cancer in children and young adults in Ukraine is strongly related to the levels of each individual's exposure to radioactive iodine, according to results reported in the July 5 JNCI.

Scientists from Ukraine, NCI's Division of Cancer Epidemiology and Genetics (DCEG), Columbia University, and other institutions analyzed data obtained from screening the thyroids of more than 13,000 children who were less than 18 years old at the time of the accident, lived in the most heavily contaminated areas of Ukraine, and had their radiation exposure to the thyroid measured by instrumentation. The analyses reported here are based on the first 2-year cycle (1998-2000) of screening for thyroid nodules by palpation and ultrasound.

Individual thyroid doses were estimated at the time of the accident based on the direct thyroid measurements and questionnaires reporting residence location and milk and food consumption, adjusted for ground contamination.

Forty-five pathologically confirmed thyroid cancers, mostly of the papillary type, were detected among 13,127 cohort members. "Exposure to radioactive iodine [¹³¹I] was strongly associated with an increased risk of thyroid cancer among those exposed as children and adolescents," the researchers report. "Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimates, yielding an estimated excess relative risk of more than five-fold per Gy." The researchers estimated that, in the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed; i.e., an increase of 75 percent over the expected value.

Younger age at exposure was associated with an increased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant. Iodine status, as measured by current urinary iodine excretion or diffuse goiter, a marker of past deficiency, did not influence risk, although it has been considered a potential modifying factor with respect to thyroid cancer.

Data from subsequent screening cycles are being analyzed to examine the risk related to newly arising versus prevalent thyroid cancers.