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AACR annual meeting 2008
News
Special Report: Conference AACR annual meeting 2008 A multicentre phase I/II dose-escalation trial in the USA has shown that the androgen-receptor agonist, MDV3100, causes significant decreases in PSA concentration in castrationresistant prostate cancer. Early findings, reported by Howard Scher and colleagues (Memorial Sloan Kettering Cancer Center, NY, USA) suggest that of 21 patients on 60 mg of MDV3100, nine patients (43%) had a greater than 50% decrease in PSA concentration from baseline. Since the trial began in December, 2007, four patients have been imaged with 18-fluorodihydrotestosterone ([18F]FDHT)-PET at baseline and at 4-week follow-up, and all scans showed no detectable uptake of the tracer. The most common adverse event was fatigue, which affected 16% of patents. The trialists plan to continue their analysis, and will report on the relation between decreases in PSA concentrations and clinical outcomes in the future.
Toremifiene prevents fractures In a phase III randomised controlled trial, toremifene significantly decreased fracture risk and improved bone-mineral density (BMD) in men with prostate cancer. Matthew Smith (Boston, MA, USA) and colleagues randomly assigned 1389 men with prostate cancer, currently receiving androgen deprivation treatment, to toremifene (80 mg/day) or placebo for 24 months. Findings showed that those on toremifene had significantly fewer new vertebral fractures than those on placebo (1·5% vs 3·5%). Toremifene also significantly increased the BMD of the spine, hip, and femoral neck, significantly decreased low-density lipoprotein and triglycerides, and increased high-density lipoprotein. However, significantly more men in the toremifene group had venous thromboembolic events than those in the placebo group http://oncology.thelancet.com Vol 9 June 2008
(17 vs 7), although this side-effect was noted predominantly in those with previous risk factors and during the first year of treatment.
Promising treatment regimen A combination of gemcitabine, oxaliplatin, and bevacizumab on days 1 and 15 of a 28-day cycle proved efficacious and well tolerated in a phase II study of women with recurrent platinumsensitive ovarian cancer. Neil Horowitz and colleagues (Boston, MA, USA) reported that this regimen produced a better-than-expected response of 60%, with nine of 15 patients having a partial response. 33% of patients had stable disease. During the trial, there was one grade 4 asymptomatic thromboembolic event and 33% of patients had grade 3 haematological toxic effects. Four women underwent serial percutaneous biopsy and intratumoral interstitialfluid pressure (IFP) measurements, and all showed a decrease in IFP. 18-fluorodeoxglucose-PET scans also showed a decrease in standard uptake values on day 15, and biomarker studies showed significant increases in placental growth factor and vascular endothelial growth factor after treatment.
Risk linked to alpha-tocopherol In a cohort study, Rachael StolzenbergSolomon and colleagues (National Cancer Institute, MD, USA) assessed the association between prediagnostic vitamin E intake, circulating concentrations of alpha-tocopherol, and exocrine pancreatic cancer in male Finnish smokers. 318 patients in the cohort were diagnosed with incident exocrine pancreatic cancer, and 306 patients were diagnosed among those with complete dietary data. Higher prediagnostic alpha-tocopherol concentrations were inversely associated with pancreatic cancer. However, intake of dietary vitamin E was not associated with pancreatic-cancer risk.
The findings were adjusted for age, smoking history, history of diabetes mellitus, and serum cholesterol. The researchers concluded that higher concentrations of serum alpha-tocopherol might have a protective role in pancreatic cancer in male smokers.
The American Association for Cancer Research 101st annual meeting was held on April 12–16, 2008, in San Diego, CA, USA
Age linked to risk of tumour Older women who smoke cigarettes are at an increased risk of developing colorectal tumours that do not have some or all of the DNA mismatch repair (MMR) proteins, according to trialists. Data presented by Paul Limburg (Rochester, MN, USA) showed that cigarette smoking status was not associated with incident colorectal cancer overall. However, the trialists also analysed tumour specimens from 30% of the 1421 women who were diagnosed with colorectal cancer. They noted that former smokers had a 61% increase in relative risk of MMR protein-negative colorectal cancer compared with never smokers, and current smokers were more than twice as likely to develop this tumour type. The association between smoking and MMR protein-negative colorectal cancer increased steadily with the number of cigarettes smoked per day.
Barbara Boughton
Zephyr/Science Photo Library
MDV3100 decreases PSA
Toremifene improves bone-marrow density in men with prostate cancer
519
Special Report: Conference AACR annual meeting 2008 A multicentre phase I/II dose-escalation trial in the USA has shown that the androgen-receptor agonist, MDV3100, causes significant decreases in PSA concentration in castrationresistant prostate cancer. Early findings, reported by Howard Scher and colleagues (Memorial Sloan Kettering Cancer Center, NY, USA) suggest that of 21 patients on 60 mg of MDV3100, nine patients (43%) had a greater than 50% decrease in PSA concentration from baseline. Since the trial began in December, 2007, four patients have been imaged with 18-fluorodihydrotestosterone ([18F]FDHT)-PET at baseline and at 4-week follow-up, and all scans showed no detectable uptake of the tracer. The most common adverse event was fatigue, which affected 16% of patents. The trialists plan to continue their analysis, and will report on the relation between decreases in PSA concentrations and clinical outcomes in the future.
Toremifiene prevents fractures In a phase III randomised controlled trial, toremifene significantly decreased fracture risk and improved bone-mineral density (BMD) in men with prostate cancer. Matthew Smith (Boston, MA, USA) and colleagues randomly assigned 1389 men with prostate cancer, currently receiving androgen deprivation treatment, to toremifene (80 mg/day) or placebo for 24 months. Findings showed that those on toremifene had significantly fewer new vertebral fractures than those on placebo (1·5% vs 3·5%). Toremifene also significantly increased the BMD of the spine, hip, and femoral neck, significantly decreased low-density lipoprotein and triglycerides, and increased high-density lipoprotein. However, significantly more men in the toremifene group had venous thromboembolic events than those in the placebo group http://oncology.thelancet.com Vol 9 June 2008
(17 vs 7), although this side-effect was noted predominantly in those with previous risk factors and during the first year of treatment.
Promising treatment regimen A combination of gemcitabine, oxaliplatin, and bevacizumab on days 1 and 15 of a 28-day cycle proved efficacious and well tolerated in a phase II study of women with recurrent platinumsensitive ovarian cancer. Neil Horowitz and colleagues (Boston, MA, USA) reported that this regimen produced a better-than-expected response of 60%, with nine of 15 patients having a partial response. 33% of patients had stable disease. During the trial, there was one grade 4 asymptomatic thromboembolic event and 33% of patients had grade 3 haematological toxic effects. Four women underwent serial percutaneous biopsy and intratumoral interstitialfluid pressure (IFP) measurements, and all showed a decrease in IFP. 18-fluorodeoxglucose-PET scans also showed a decrease in standard uptake values on day 15, and biomarker studies showed significant increases in placental growth factor and vascular endothelial growth factor after treatment.
Risk linked to alpha-tocopherol In a cohort study, Rachael StolzenbergSolomon and colleagues (National Cancer Institute, MD, USA) assessed the association between prediagnostic vitamin E intake, circulating concentrations of alpha-tocopherol, and exocrine pancreatic cancer in male Finnish smokers. 318 patients in the cohort were diagnosed with incident exocrine pancreatic cancer, and 306 patients were diagnosed among those with complete dietary data. Higher prediagnostic alpha-tocopherol concentrations were inversely associated with pancreatic cancer. However, intake of dietary vitamin E was not associated with pancreatic-cancer risk.
The findings were adjusted for age, smoking history, history of diabetes mellitus, and serum cholesterol. The researchers concluded that higher concentrations of serum alpha-tocopherol might have a protective role in pancreatic cancer in male smokers.
The American Association for Cancer Research 101st annual meeting was held on April 12–16, 2008, in San Diego, CA, USA
Age linked to risk of tumour Older women who smoke cigarettes are at an increased risk of developing colorectal tumours that do not have some or all of the DNA mismatch repair (MMR) proteins, according to trialists. Data presented by Paul Limburg (Rochester, MN, USA) showed that cigarette smoking status was not associated with incident colorectal cancer overall. However, the trialists also analysed tumour specimens from 30% of the 1421 women who were diagnosed with colorectal cancer. They noted that former smokers had a 61% increase in relative risk of MMR protein-negative colorectal cancer compared with never smokers, and current smokers were more than twice as likely to develop this tumour type. The association between smoking and MMR protein-negative colorectal cancer increased steadily with the number of cigarettes smoked per day.
Barbara Boughton
Zephyr/Science Photo Library
MDV3100 decreases PSA
Toremifene improves bone-marrow density in men with prostate cancer
519