Heme/Onc News

Pfizer Wins U.S. FDA Approval for Advanced Kidney-Cancer Treatment Inlyta
Pfizer Inc. (PFE), the world’s biggest drugmaker, won U.S. clearance to sell a new medicine for advanced kidney cancer in patients who have failed prior treatments. The Food and Drug Administration approved the drug, Inlyta, after concluding it helps prevent the cancer from progressing, the agency said today in a statement. Inlyta, known chemically as axitinib, worked better than Nexavar in a comparative study of 723 patients who had failed one prior therapy. Those treated with Inlyta lived a median of 6.7 months before their tumors got worse, two months longer than patients who received Nexavar, the FDA said.

Cancer rates in U.S. keep falling
Cancer death rates are continuing to fall, dropping by 1.8 percent per year in men and 1.6 percent per year in women between 2004 and 2008, according to the American Cancer Society's annual report on cancer statistics released on Wednesday

Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron

The controversy of varicella vaccination in children with acute lymphoblastic leukemia
The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered a reasonable option. There is little available data to allow a comparison of the risk versus benefit of vaccinating these patients. This retrospective review showed that the negligible rate of fatal varicella infection in children with ALL, the risk that accompanies vaccination, and the necessity of withholding chemotherapy for vaccination appear to outweigh the potential benefit of varicella vaccination for children during treatment of ALL.

Mobile phones don't hike cancer risk: Danish study
The results, released on the British Medical Journal's website, chime with a series of other studies that have reached similar conclusions. Scientists from the Institute of Cancer Epidemiology in Copenhagen looked at people aged at least 30 who subscribed to mobile phone contracts and compared their rates of brain tumors with non-subscribers between 1990 and 2007. Outside experts said the large scale of the trial was impressive.

Panel Says Prostate Test Does Not Save Lives
Healthy men do not need prostate cancer screening with prostate specific antigen (PSA) because the test does not save lives and often leads to unnecessary testing, interventions, and treatment, the United States Preventive Services Task Force (USPSTF) is expected to recommend in an update to its prostate cancer screening guidelines. According to a report in the New York Times, the recommendation will be announced Tuesday and is based on a USPSTF-commissioned study, which failed to show a clear benefit from prostate cancer screening with PSA.

Alcohol drinking and colorectal cancer risk
The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2–3 drinks/day) alcohol drinking, investigation of the dose–response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region. This article looked at twenty-seven cohort and 34 case–control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.

Contralateral prophylactic mastectomy in breast cancer patients who test negative for BRCA mutations
Determination of BRCA1 and 2 mutation carrier status is important. Although BRCA carriers are offered bilateral mastectomy and oophorectomy, most who test negative decline. Some women choose contralateral prophylactic mastectomy (CPM) at the time of their breast cancer diagnosis despite testing negative. A total of 110 women with breast cancer received genetic testing before surgical treatment. Patient demographics, tumor characteristics, surgical treatment, and magnetic resonance imaging use were recorded. This article found Increased rates of CPM have been observed and that married women were more likely to choose CPM. We recommend genetic genotyping before surgery. These findings warrant further investigation.

Screening has little impact on breast cancer deaths
Researchers analyzed data from three pairs of countries in Europe and found that although breast cancer screening programs had been introduced 10 to 15 years earlier in some areas than in others, declines in death rates were similar. The findings suggest that "improvements in treatment and in the efficiency of healthcare systems may be more plausible explanations" for falling deaths rates from breast cancer, they wrote in a study in the British Medical Journal. World Health Organization (WHO) data show that deaths from breast cancer are decreasing in the United States, Australia, and most Nordic and western European countries but breast screening is a hot topic among experts who disagree about whether nationwide mammogram programs do more harm than good. Annals of Oncology Abstract

A prognostic model for short term adverse events in normotensive patients with pulmonary embolism
Risk stratification of patients with PE has gained interest in terms of the identification of patients in whom treatment on an outpatient base can be considered. Previous studies are of limited value due to their focus on adverse clinical events within several months after diagnosis of PE. We developed a prognostic model, based on easily accessible, clinical, and laboratory parameters, to predict adverse events during the first 10 days after the diagnosis of acute PE. The final prognostic model to predict short-term adverse events consists of NT-proBNP levels, D-dimer concentrations, pulse rate, and the occurrence of active malignancy; the total score ranges from 0 to 37 points. Patients with a low score (no active malignancy, pulse rate <90 bpm, NT-proBNP <500 pg/ml, and D-dimer <3,000 μg/l FEU) have a 10-day adverse event risk <1.5%. This risk increases to over 30% in patients with a maximum score, based on high pulse rate, D-dimer concentrations, and NT-proBNP levels. Our prognostic model, once prospectively validated in an independent sample of patients, can be used in the early risk stratification of PE to estimate the risk of adverse events and to differentiate between candidates for in- or out- hospital treatment.

New Treatment for Multiple Myeloma Shows Promise
The combination of lenalidomide and low-dose dexamethasone is an effective treatment for multiple myeloma (MM). Addition of alkylating agents to lenalidomide or thalidomide results in increased response rates and deeper responses. The authors of this article designed this trial to study the combination of cyclophosphamide, lenalidomide, and dexamethasone (CRd) as initial therapy for MM. Fifty-three patients with previously untreated symptomatic MM was enrolled. Patients received 4-week treatment cycles consisting of lenalidomide (25 mg daily for 3 weeks), dexamethasone (40 mg weekly), and cyclophosphamide (300 mg/m2 weekly for 3 weeks). A partial response or better was seen in 85% of patients including 47% with a very good partial response or better. The toxicities were manageable with over 80% of planned doses delivered; six patients went off study for toxicity. The median progression free survival (PFS) for the entire group was 28 months and the overall survival (OS) at 2 years was 87%. Importantly, 14 patients with high-risk MM had similar PFS and OS as the standard-risk patients. CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy.

Medicare will keep covering Roche's Avastin
The statement from the U.S. healthcare program could mitigate concerns that patients using the drug would lose insurance coverage should the U.S. Food and Drug Administration revoke approval for its use in breast cancer. An FDA panel recommended on Wednesday that Avastin no longer be used to treat the disease because it has not proven safe or clinically beneficial in large trials. FDA Commissioner Margaret Hamburg is expected to make a final decision later this year. Doctors can still prescribe Avastin if the FDA revokes approval, but the move would influence recommendations by physician and insurance groups over whether to pay for it. "The drug will still be on the market, doctors will still be prescribing it, and we will continue to pay for it," he said, adding that CMS often pays for off-label uses of drugs.

Better Evidence about Screening for Lung Cancer
In October 2010, the National Cancer Institute (NCI) announced that patients who were randomly assigned to screening with low-dose computed tomography (CT) had fewer deaths from lung cancer than did patients randomly assigned to screening with chest radiography. The first report of the NCI-sponsored National Lung Screening Trial (NLST) in a peer-reviewed medical journal appears in this issue of the Journal.

Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival
Survival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. This article was an Exploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008. Overall it showed that Young patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.

Pregnancy-associated breast cancer is as chemosensitive as non-pregnancy-associated breast cancer in the neoadjuvant setting
 The aim of this study was to determine the chemosensitivity of pregnancy-associated breast cancer (PABC) in the neoadjuvant setting by comparing the observed pathological complete response (pCR) rate with the rate predicted by a validated nomogram. Data from 48 PABC patients who received neoadjuvant chemotherapy (NACT) were collected. To predict the response rate to chemotherapy, we used well-calibrated logistic regression-based nomograms to calculate individual probability of pCR.  Through the use of nomograms, our study demonstrates that PABC is as chemosensitive as non-PABC and suggests that taxanes should be part of the NACT regimen for PABC. Further studies are warranted to increase the power of the presented data.

Chemo Length May Not Affect Survival in Some B-cell Lymphomas
It doesn’t seem to matter whether patients with newly diagnosed, diffuse large B-cell lymphoma receive a standard chemotherapy regimen in a dose-dense fashion every 14 days for six cycles, or every 21 days for eight cycles, said investigators in a multinational trial that was presented at the annual meeting of the American Society of Clinical Oncology. There were no significant differences in the primary outcome of overall survival or the secondary outcome of failure-free survival among 1,080 patients who were randomly assigned to the two R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens, reported Dr. David Cunningham of the Royal Marsden Hospital in London, on behalf of colleagues in the U.K. National Cancer Research Institute’s lymphoma clinical study group.

Updated warfarin guidelines released
The British Committee for Standards in Haematology has published updated guidelines on oral anticoagulation with warfarin. The guidelines replace those published in 2006 and should provide healthcare professionals with clear guidance on the indications for and management of patients on warfarin, say the authors. To make the current recommendations, the writing group, led by David Keeling (Oxford Radcliffe Hospitals, UK), reviewed data from clinical trials and meta-analyses published in the last 5 years. They covered areas such as the indications for warfarin and the recommended target international normalized ratio (INR), duration of anticoagulation, management of bleeding, and anticoagulant monitoring and dose adjustment.

Melanoma Survival Benefit Called 'Astounding'
 Patients with metastatic melanoma had an "astounding" 63% reduction in the risk of death when treated with an investigational agent that targets a mutation found in about half of the tumors, data from a large international trial showed. Treatment with the BRAF inhibitor vemurafenib improved progression-free survival (PFS) by 74%. Analysis of six-month overall survival (OS) showed a 20% absolute difference between patients treated with vemurafenib versus dacarbazine. Though follow up is brief, the results already make a case for vemurafenib as the comparator for future trials of new agents for advanced melanoma, Paul. B. Chapman, MD, of Memorial Sloan-Kettering Cancer Center in New York City, said at the American Society of Clinical Oncology meeting.

Effect of Screening on Ovarian Cancer Mortality
Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. The authors sought to evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Randomized controlled trial of 78 216 women aged 55 to 74 years assigned to undergo either annual screening or usual care at 10 screening centers across the United States between November 1993 and July 2001. Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications.

Early prostate cancer – which treatment do men prefer and why?
In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients’ views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient’s final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n = 63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle.

Biomarkers for early detection of sickle nephropathy
Renal complications affect nearly 30-50% of adults with sickle cell anemia (SCA), causing significant morbidity and mortality. Standard renal function tests like serum creatinine and glomerular filtration rate become abnormal in this disease only when renal damage has become extensive and largely irreversible. Moreover, not all patients develop sickle nephropathy (SN). Therefore, non-invasive biomarkers that predict early onset of SN are necessary. We performed a cross-sectional analysis for nephropathy in 116 patients with sickle cell disease, analyzing urinary kidney injury molecule–1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β1 (TGF-β), together with conventional renal biomarkers (urine albumin and osmolality, and serum creatinine and cystatin C estimated GFR) during routine clinic visits when patients were at steady-state/baseline. We observed a distinct biomarker pattern: KIM-1 and NAG emerged as biomarkers with a strong association with albuminuria. Surprisingly, and in contrast to other acute/chronic renal disorders, NGAL, L-FABP and TGF-β levels did not show any relationship with albuminuria in patients with SCA. Our study identifies potential biomarkers for SN, and suggests longitudinal validation of these biomarkers for early detection of SN, so that therapeutic interventions can be applied before renal damage becomes irreversible.  For More Hem/Onc News Visit Our Hem/Onc Archives