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Ondansetron to treat early-onset alcoholism?
SCIENCE AND MEDICINE
Caution over use of lung-cancer screening as standard practice
A
n extended follow-up study (median 20·5 years) of the Mayo Lung Project (MLP) shows no mortality reduction in the intervention arm (chest radiograph and sputum cytology every 4 months for 6 years) compared with individuals advised at trial entry to be screened annually, although median survival was longer in the intervention arm (J Natl Cancer Inst 2000; 92: 1308–16). Mortality is considered to be the critical measure of screening efficiency, and the authors conclude that a major factor in this discrepancy was overdiagnosis bias, a phenomenon that confounds survival data but has no effect on mortality. The design of MLP (conducted between 1971 and 1983 in 9211 male smokers) has been heavily criticised, especially as the trial had only a 48% power to detect what is now held to be a reasonable reduction in mortality (20%). The other main criticism was that the average follow-up of 3 years was too short. “Many critics of the original data thought that extended follow-up might reveal a reduction in mortality, but we were not surprised that our findings confirmed no reduction in mortality”, says Pamela Marcus (Division of
New hope for thyroid cancer fusion protein (PAX8-PPAR␥1) found only in thyroid follicular carcinomas could aid the diagnosis and treatment of thyroid cancer (Science 2000; 289: 1357–60). “Chromosomal translocations that encode fusion oncoproteins are well known in leukaemias and sarcomas, but they have been identified previously in only one adult (thyroid papillary) carcinoma”, says lead author Todd Kroll (Harvard Medical School, Boston, MA, USA) “PAX8PPAR␥1 could aid the differential diagnosis of malignant thyroid follicular carcinomas from benign follicular adenomas in biopsy specimens.” The hope is, he adds, that PAX8PPAR␥1 and molecular markers will identify thyroid malignancies for definitive treatment and reduce the need to resect benign thyroid tumours to exclude the possibility of malignancy, thereby reducing the overall need for thyroid surgery.
A
Dorothy Bonn
742
Cancer Prevention, National Cancer Institute, Bethesda, MD, USA). “The most likely explanation for the difference in survival and mortality data is that screening detected
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Will spiral CT make x-ray obsolete?
lesions with limited clinical relevance that did not adversely affect the lifespan of the patient—this is known as overdiagnosis bias”, explains Marcus. “Most lung cancers are detected symptomatically, and these people die of their disease; however, it is plausible that indolent lung cancers exist and are only
detectable by screening.” The dangers of overdiagnosis in other cancers, including prostate cancer, are just beginning to be realised. The NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is randomising participants in the lung group to annual radiography or no recommendation for screening and has ample statistical power to detect a 10–20% reduction in lung cancer mortality. Advances in screening modalities, such as introduction of spiral computed tomography, might further improve the detection of early-stage disease. In September, the NCI is enrolling patients into the Lung Screening Study, which is a feasibility study to determine whether a large randomised clinical trial of spiral CT versus radiography screening is possible. “Spiral CT is a very powerful technique with much greater resolution than radiographs”, says Marcus. “However, before it becomes standard medical practice we need to make sure that detecting early lung cancer lesions will not do more harm than good.” Ezzie Hutchinson
Ondansetron to treat early-onset alcoholism? he anti-emetic, ondansetron, may have another clinical use—treatment of early-onset alcoholism, report US researchers (JAMA 2000; 284: 963–71, 1016–17). Bankole A Johnson (University of Texas Health Science Center, San Antonio, TX, USA) and colleagues randomised 271 patients aged 25–65 years with DSMIII alcoholism to receive the 5-HT3receptor antagonist at 1 g/kg, 4 g/kg, 16 g/kg, or identical placebo twice daily for 11 weeks. All patients also participated in weekly group cognitive behavioural therapy. Johnson’s team found that patients whose alcoholism had developed before age 25 and who had taken ondansetron reported significantly less alcohol consumption than those who had received placebo. This effect was most marked in patients with early-onset disease who took the 4 g/kg dose with regard to percentage of days abstinent (70·10 vs 50·20; p=0·02) and days abstinent per study week (6·74 vs 5·92; p=0·03). This difference was confirmed by measurement of plasma carbohydrate-
T
deficient transferrin concentration—a sensitive marker for transient alcohol consumption. Ondansetron had no such effect in participants whose alcoholism had started after age 25 years. “Efficacy of such small ondansetron dosages in treating patients with earlyonset alcoholism is consistent with animal studies of its antirewarding effects on ethanol consumption, and strenghthen the proposal that 5-HT3 receptors are an important site of alcohol’s brain effects”, the researchers write. “Based on these findings, ondansetron could be used to treat patients with early onset alcoholism, whereas a selective serotonin reuptake inhibitor might be used in patients with low-risk or low-severity alcoholism, a group that is characterized by late onset of alcohol dependence”, writes Henry R Kranzler (Alcohol Research Center, Farmington, CT, USA) in an accompanying editorial, adding that the results need to be replicated. Sarah Ramsay
THE LANCET • Vol 356 • August 26, 2000
For personal use only. Not to be reproduced without permission of The Lancet.
Caution over use of lung-cancer screening as standard practice
A
n extended follow-up study (median 20·5 years) of the Mayo Lung Project (MLP) shows no mortality reduction in the intervention arm (chest radiograph and sputum cytology every 4 months for 6 years) compared with individuals advised at trial entry to be screened annually, although median survival was longer in the intervention arm (J Natl Cancer Inst 2000; 92: 1308–16). Mortality is considered to be the critical measure of screening efficiency, and the authors conclude that a major factor in this discrepancy was overdiagnosis bias, a phenomenon that confounds survival data but has no effect on mortality. The design of MLP (conducted between 1971 and 1983 in 9211 male smokers) has been heavily criticised, especially as the trial had only a 48% power to detect what is now held to be a reasonable reduction in mortality (20%). The other main criticism was that the average follow-up of 3 years was too short. “Many critics of the original data thought that extended follow-up might reveal a reduction in mortality, but we were not surprised that our findings confirmed no reduction in mortality”, says Pamela Marcus (Division of
New hope for thyroid cancer fusion protein (PAX8-PPAR␥1) found only in thyroid follicular carcinomas could aid the diagnosis and treatment of thyroid cancer (Science 2000; 289: 1357–60). “Chromosomal translocations that encode fusion oncoproteins are well known in leukaemias and sarcomas, but they have been identified previously in only one adult (thyroid papillary) carcinoma”, says lead author Todd Kroll (Harvard Medical School, Boston, MA, USA) “PAX8PPAR␥1 could aid the differential diagnosis of malignant thyroid follicular carcinomas from benign follicular adenomas in biopsy specimens.” The hope is, he adds, that PAX8PPAR␥1 and molecular markers will identify thyroid malignancies for definitive treatment and reduce the need to resect benign thyroid tumours to exclude the possibility of malignancy, thereby reducing the overall need for thyroid surgery.
A
Dorothy Bonn
742
Cancer Prevention, National Cancer Institute, Bethesda, MD, USA). “The most likely explanation for the difference in survival and mortality data is that screening detected
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Will spiral CT make x-ray obsolete?
lesions with limited clinical relevance that did not adversely affect the lifespan of the patient—this is known as overdiagnosis bias”, explains Marcus. “Most lung cancers are detected symptomatically, and these people die of their disease; however, it is plausible that indolent lung cancers exist and are only
detectable by screening.” The dangers of overdiagnosis in other cancers, including prostate cancer, are just beginning to be realised. The NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is randomising participants in the lung group to annual radiography or no recommendation for screening and has ample statistical power to detect a 10–20% reduction in lung cancer mortality. Advances in screening modalities, such as introduction of spiral computed tomography, might further improve the detection of early-stage disease. In September, the NCI is enrolling patients into the Lung Screening Study, which is a feasibility study to determine whether a large randomised clinical trial of spiral CT versus radiography screening is possible. “Spiral CT is a very powerful technique with much greater resolution than radiographs”, says Marcus. “However, before it becomes standard medical practice we need to make sure that detecting early lung cancer lesions will not do more harm than good.” Ezzie Hutchinson
Ondansetron to treat early-onset alcoholism? he anti-emetic, ondansetron, may have another clinical use—treatment of early-onset alcoholism, report US researchers (JAMA 2000; 284: 963–71, 1016–17). Bankole A Johnson (University of Texas Health Science Center, San Antonio, TX, USA) and colleagues randomised 271 patients aged 25–65 years with DSMIII alcoholism to receive the 5-HT3receptor antagonist at 1 g/kg, 4 g/kg, 16 g/kg, or identical placebo twice daily for 11 weeks. All patients also participated in weekly group cognitive behavioural therapy. Johnson’s team found that patients whose alcoholism had developed before age 25 and who had taken ondansetron reported significantly less alcohol consumption than those who had received placebo. This effect was most marked in patients with early-onset disease who took the 4 g/kg dose with regard to percentage of days abstinent (70·10 vs 50·20; p=0·02) and days abstinent per study week (6·74 vs 5·92; p=0·03). This difference was confirmed by measurement of plasma carbohydrate-
T
deficient transferrin concentration—a sensitive marker for transient alcohol consumption. Ondansetron had no such effect in participants whose alcoholism had started after age 25 years. “Efficacy of such small ondansetron dosages in treating patients with earlyonset alcoholism is consistent with animal studies of its antirewarding effects on ethanol consumption, and strenghthen the proposal that 5-HT3 receptors are an important site of alcohol’s brain effects”, the researchers write. “Based on these findings, ondansetron could be used to treat patients with early onset alcoholism, whereas a selective serotonin reuptake inhibitor might be used in patients with low-risk or low-severity alcoholism, a group that is characterized by late onset of alcohol dependence”, writes Henry R Kranzler (Alcohol Research Center, Farmington, CT, USA) in an accompanying editorial, adding that the results need to be replicated. Sarah Ramsay
THE LANCET • Vol 356 • August 26, 2000
For personal use only. Not to be reproduced without permission of The Lancet.