Heme/Onc News
Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a debilitating and life-threatening disease in which lysis of PNH red blood cells frequently manifests with chronic hemolysis, anemia, and thrombosis. Renal damage in PNH is associated with chronic hemosiderosis and/or microvascular thrombosis. We determined the incidence of renal dysfunction or damage, defined by stages of chronic kidney disease (CKD), in a large cohort of PNH patients and evaluated the safety and efficacy of the complement inhibitor eculizumab in altering its progression. Renal dysfunction or damage was observed in 65% of the study population at baseline with 21% of patients with later stage CKD or kidney failure (glomerular filtration rate [GFR] 60 ml/min/1.73 m2; Stage 3, 4, or 5). Eculizumab treatment was safe and well-tolerated in patients with renal dysfunction or damage and resulted in the likelihood of improvement as defined as categorical reduction in CKD stage (P < 0.001) compared with baseline and to placebo (P = 0.04). Improvement in renal function was more commonly seen in patients with baseline CKD Stages 1-2 (67.1% improvement, P < 0.001) although improvement was also observed in patients with CKD Stages 3-4 (P = 0.05). Improvements occurred quickly and were sustained for at least 18 months of treatment. Patients categorized at CKD Stages 3-5 did not worsen during treatment with eculizumab. Overall, 40 (21%) of 195 patients who demonstrated renal dysfunction or damage at baseline were no longer classified as such after 18 months of treatment. Administration of eculizumab to patients with renal dysfunction or damage was well tolerated and was usually associated with clinical improvement.
Colorectal cancer screening test more accurate in winter than summer
Study results show that the immunochemical fecal occult blood test (iFOBT) for detecting colorectal cancer is approximately 13% less accurate in the summer than in the winter. In this study, Grazia Grazzini (Cancer Prevention and Research Institute, Florence, Italy) and colleagues analyzed 199,654 iFOBT results taken as part of the Florence regional colorectal cancer screening program. Overall, the researchers found that there was a 13% lower probability of detecting a cancer or an advanced adenoma with iFOBT in the summer than the winter. Writing in the journal Gut, the investigators warn: "These results will have important implications for the organization of iFOBT-based screening programs, particularly in countries with high ambient temperatures."
Angiotensin Receptor Blockers (ARBs): Ongoing Safety Review for Cancer Risk
A recently published study - a meta-analysis combining cancer-related findings from several clinical trials - suggested use of ARBs may be associated with a small increased risk of cancer. The meta-analysis included data from over 60,000 patients in several long-term, randomized, controlled clinical trials evaluating ARBs for which adverse events related to cancer were captured during the study. The mean duration of follow-up ranged from 1.7 to 4.8 years.The study reported the frequencies of new cancer occurrence to be 7.2% for patients receiving ARBs compared to 6.0% for those not receiving ARBs (risk ratio = 1.08, 95% Confidence Interval: 1.01-1.15).FDA has not concluded that ARBs increase the risk of cancer. The Agency is reviewing information related to this safety concern and will update the public when additional information is available. FDA believes the benefits of ARBs continue to outweigh their potential risks.
Tamoxifen Infrequently Used by Women at Risk for Breast Cancer
The prevalence of tamoxifen use for the primary prevention of breast cancer is "exceptionally low" among women in the United States, according to an analysis of National Health Interview Survey (NHIS) data published recently in Cancer Epidemiology, Biomarkers & Prevention (2010;19:443-446).
According to results of the Breast Cancer Prevention Trial published in 1998, tamoxifen reduced the risk of developing invasive breast cancer by 49%, and the relative risk reduction for estrogen receptor-positive invasive breast cancer was 69% (J Natl Cancer Inst. 1998;90:1371-1988). Despite this substantial risk reduction, subsequent studies have indicated that tamoxifen is used for chemoprevention by only a very small percentage of eligible women.
Zoledronic Acid Plus Chemo Prior to Breast Cancer Surgery Reduces Number of Tumour Cells
When zoledronic acid is given along with chemotherapy for 3 months before breast cancer surgery, it reduced the number of women who had tumour cells in their bone marrow at the time of surgery, according to a study published in the May issue of The Lancet Oncology.
"Bone marrow seems to be a DTC [disseminated tumour cells] sanctuary, allowing them to adapt and disseminate to different organs, where they're a leading cause of death," said lead author Rebecca Aft, MD, Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri. "We believe that zoledronic acid inhibits the release of growth factors that help support the growth of DTCs."
Shark Cartilage Not Beneficial in Advanced Lung Cancer
A drug derived from shark cartilage failed to improve survival in patients with advanced lung cancer, researchers report. The disappointing results, which came in the final stage of testing, showed that the drug didn't help extend the life spans of patients with inoperable stage III non-small cell lung cancer.Scientists have been testing drugs derived from shark cartilage because it appears to prevent blood vessels from growing around tumors. The hope is that the drugs will prevent cancer cells from being fed by blood, which allows them to grow.
The risks and benefits of long-term use of hydroxyurea in sickle cell anemia
A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure.
Aromatase inhibition in male breast cancer patients: biological and clinical implications
The role of aromatase inhibitors (AIs) and their impact on estradiol (E2) levels remain unknown in male breast cancer (MBC) patients. MBC patients with metastatic disease and those treated with AIs were selected from the breast cancer database of the Centre Antoine-Lacassagne (Nice, France). This study found that Aromatase Inhibitors are active in MBC patients. This activity is correlated with a significant reduction in E2 levels. Secondary resistance is in part related to a deleterious feedback loop resulting in a significant increase in substrate for aromatization.
Statins Won't Lower Colon Cancer Risk
Statins don't lower the risk of colorectal cancer, and may even increase the chances of developing precancerous polyps, new research suggests. We found patients in this study taking statins for more than three years tended to develop more premalignant colon lesions," said study author Dr. Monica Bertagnolli, chief of the division of surgical oncology at Brigham and Women's Hospital and a professor of surgery at Harvard Medical School. "This is an interesting finding that needs to be followed up, but it should not raise alarm. No one should stop taking their statins."
Long term, tamoxifen stops more cancer than Evista
After nearly seven years of follow-up, researchers found that women who took tamoxifen for five years were less likely to develop breast cancer than those who took Evista, known generically as raloxifene. But they told a meeting of the American Association for Cancer Research that both drugs are useful and that women should be able to choose. Only tamoxifen is approved for women who have not yet gone through menopause, and many may not want to risk its side effects.
Free light chain: a novel predictor of adverse outcome in chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. This retrospective study in this months European Journal of Haematology assessed the prognostic value of serum free light chain (sFLC) levels and FLC ratio (FLCR) in CLL. It found the median time to first treatment was shorter in patients with high sFLC levels and overall survival was shorter in patients with high sFLC levels concluding an adverse prognostic impact of high sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage patients. Prospective studies are warranted to validate the adverse impact of sFLC and FLCR on clinical outcome.
Lipid levels in sickle-cell disease associated with haemolytic severity, vascular dysfunction and pulmonary hypertension
Pulmonary hypertension (PH) in sickle cell disease (SCD) is an emerging and important clinical problem. In a single-institution adult cohort of 365 patients, we investigated lipid and lipoprotein levels and their relationship to markers of intravascular haemolysis, vascular dysfunction and PH. In agreement with prior studies, we confirm significantly decreased plasma levels of total cholesterol, high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in SCD versus ethnically-matched healthy controls. Several cholesterol parameters correlated significantly with markers of anaemia, but not endothelial activation or PH. More importantly, serum triglyceride levels were significantly elevated in SCD compared to controls. Elevated triglyceride levels correlated significantly with markers of haemolysis, endothelial activation, inflammation and PH; prevalence of elevated tricuspid regurgitant velocity.
Is statin use associated with prostate cancer aggressiveness?
To further examine the association between statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) and pathological features in a large group of patients undergoing radical prostatectomy (RP), as epidemiological studies have suggested that statins, in addition to their beneficial cardiovascular effects, might reduce the risk of aggressive prostate cancer.From 2003 to 2009, 1351 men with data on preoperative statin use had RP by one surgeon. The clinical and pathological tumour features were compared between 504 users of statins and 847 who were not users.The preoperative serum prostate-specific antigen levels, tumour volume and percentage of cancer in the RP specimen were significantly lower in patients taking statins. Overall, statin users had a proportionately lower rate of adverse tumour pathology features, including a significantly lower risk of positive (cancerous) surgical margins.
Radiation Most Effective Soon After Breast Cancer Surgery
For women who have had breast cancer surgery, the question of whether or not to wait before receiving radiation therapy has been answered by new research that suggests that the longer women wait, the greater the chance of cancer recurrence. The findings, published in the March 3 online edition of BMJ, are based on an analysis of national cancer records for 18,050 American women who were diagnosed with early-stage breast cancer between 1991 and 2002, at age 65 or older.
Radiation After Mastectomy May Be Overused
Many women who undergo mastectomy for early-stage breast cancer may not benefit from radiotherapy, a retrospective study suggested.
Among those who had stage I or II disease with spread to no more than three lymph nodes and who did not undergo radiation therapy, the overall locoregional recurrence rate was just 2.3% at 10 years, according to Ranjna Sharma, MD, of the University of Texas M.D. Anderson Cancer Center in Houston.
Hormone replacement tied to lung cancer risk
Women who use hormone replacement therapy combining estrogen and progestin may have a higher risk of lung cancer than non-users, a new study finds.Whether hormone replacement therapy (HRT) itself is to blame is not certain, researchers say. But the findings add to the complicated mix of potential health effects of HRT. The study, published in the Journal of Clinical Oncology, looked at new lung cancer diagnoses among more than 36,000 women ages 50 to 75 who were followed over six years. During that time, 344 women developed the cancer.
Accelerated, hypofractionated radiation therapy successfully treats breast cancer
An intense 3-week course of radiation therapy is just as effective as the standard 5-week regimen for women with early-stage breast cancer, Canadian research shows. “For women with breast cancer who are similar to the patients in this trial, an abbreviated course of radiation therapy should be more convenient and less costly than standard treatment,” remark Timothy Whelan (Juravinski Cancer Centre, Hamilton, Ontario) and co-authors in the New England Journal of Medicine.
Aspirin cuts death risk after breast cancer: U.S. study
"This is the first study to find that aspirin can significantly reduce the risk of cancer spread and death for women who have been treated for early stage breast cancer, " said Dr. Michelle Holmes of Harvard Medical School, who led the study published in the Journal of Clinical Oncology.
Tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer shows to be effective
In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear. A study out of the Annals of Oncology was done where premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved Disease Free Survival [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved Overall Survival (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup.
Scientists find new leukemia gene risk factors
LONDON (Reuters) - Researchers have found four new genetic variants that increase the risk of contracting one of the major forms of leukemia, confirming that risk factors for the fatal blood cancer can be inherited. The findings mean scientists now know of 10 genetic variants associated with chronic lymphocytic leukemia (CLL), scientists at Europe's Institute of Cancer Research who conducted the study said. The four new genetic factors are all common in European populations and each factor contributes to an increase in the risk of the disease.
Pomegranate Compounds May Prevent Breast Cancer Growth
US researchers found that pomegranates contain six natural compounds that may prevent the growth of hormone-dependent breast cancer by blocking the enzyme aromatase, which changes androgen to estrogen. However, experts caution this does not mean people should expect the same results from eating pomegranates, because this was an "in vitro" (test tube) study and results on the lab bench don't always translate to animals and humans.
Melanoma in Blacks and White Hispanics Found in Later Stages Than Whites Non-Hispanics
Archives of Dermatology
A study examining and comparing the temporal trends in melanoma incidence and stage at diagnosis among whites, Hispanics, and blacks in Florida from 1990 to 2004 was conducted. Of 41 072 cases of melanoma, 39 670 cases were reported for white non-Hispanics (WNHs), 1148 for white Hispanics (WHs), and 254 for blacks. Both WHs and blacks had significantly more advanced melanoma at presentation: 18% of WH and 26% of black patients had either regional or distant-stage melanoma at diagnosis compared with 12% of WNH patients. The proportion of distant-stage melanoma diagnosed among WHs and blacks changed little from 1990 to 2004, compared with a steady decrease in the percentage of melanoma cases diagnosed at distant stage among WNHs.
