Scienceweekly

2007-07-22T02:38:00.000-07:00

Improved progression-free, but not overall survival with fludarabine plus cyclophosphamide in patients with chronic lymphocytic leukemia

Researchers in the United Kingdom have reported increased progression-free, but not overall survival with fludarabine plus cyclophosphamide in patients with chronic lymphocytic leukemia (CLL), in a study presented in The Lancet this week.

In this study, 777 patients with CLL received fludarabine plus cyclophosphamide, fludarabine alone, or chlorambucil alone. There was no significant difference in overall survival between all three treatments groups. Complete and overall response rates (CR and ORR) were significantly higher with fludarabine plus cyclophosphamide than with fludarabine (CR: 38% vs 15%, respectively; ORR: 94% vs 80%, respectively; p<0•0001), which were significantly higher than with chlorambucil (CR: 7%; ORR: 72%; p=0•006 and 0•04, respectively). Progression-free survival was significantly higher with fludarabine plus cyclophosphamide than with fludarabine or chlorambucil (36% vs 10% vs 10%, respectively; p<0•00005).

A meta-analysis of data from this study and of two other Phase III trials showed a consistent benefit with fludarabine plus cyclophosphamide in terms of progression-free survival.

Author’s conclusions: fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.

Source: http://www.thelancet.com/journals/lancet/article/PIIS0140673607611258/abstract

2007-07-21T05:18:00.000-07:00

AZD2171 (RECENTIN™) shows promising anti-tumour activity in advanced solid tumours

Researchers have reported that AZD2171 (RECENTIN™; AstraZeneca) shows promising anti-tumour activity and is generally well-tolerated in various advanced solid tumours, in a study reported in the Journal of Clinical Oncology this week.

AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling, thereby inhibiting tumour angiogenesis.

This Phase I study consisted of two parts. In part A, 36 patients with advanced solid tumours and liver metastases received al AZD2171 0.5 to 60 mg, once daily to identify the maximum tolerated dose. In part B, 36 patients with and 11 patients without liver metastases received oral AZD2171 (20, 30 or 45 mg). Patients continued to receive treatment until tumour progression or dose-limiting toxicity occurred.

Eighty-three patients received AZD2171, which was generally well-tolerated up to a dose of 45 mg/day. Most frequently reported adverse events included diarrhea, dysphonia and hypertension, and the most common dose-limiting toxicity was hypertension in 7/83 (8.4%) patients at doses ≥ 20 mg.

Maximum peak drug concentrations after a single dose of AZD2171 occurred between 1 and 8 hours post-AZD2171 administration with a mean half-life of 22 hours.

Promising anti-tumour activity was observed with two (2.4%) patients achieving confirmed partial responses and 22 (26.5) patients achieving stable disease.

Author’s conclusions: Once-daily oral AZD2171 at doses of ≤45 mg was generally well tolerated and associated with encouraging anti-tumour activity in patients with a broad range of advanced solid tumours.

Additional information: a number of clinical trials of AZD2171 as a single-agent or in combination with other agents in various solid tumours are ongoing (follow link below)

http://www.astrazenecaclinicaltrials.com/article/516060.aspx

Source: http://jco.ascopubs.org/cgi/content/abstract/25/21/3045

2007-06-20T09:23:00.000-07:00

Yttrium-90 ibritumomab tiuxetan is clinically active in patients with advanced diffuse large B-cell lymphoma ineligible for stem-cell transplantation

Researchers have reported that yttrium-90 ibritumomab tiuxetan (Zevalin®; Biogen Idec, Bayer Schering Pharma) has clinical activity in patients with advanced diffuse large B-cell lymphoma who were unable to undergo stem-cell transplantation, in a study reported in the journal Blood this week.

Yttrium-90 ibritumomab tiuxetan is a monoclonal antibody bound via a linker (tiutexan) to the radioisotopes Yttrium-90 or Indium-11, targeting the CD20 antigen on normal and malignant B-lymphocytes. As a result, radiation is directed against CD20 positive cells, inducing cellular damage on the target and neighboring cells.

Yttrium-90 ibritumomab tiuxetan is currently indicated for for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with rituximab-refractory follicular NHL.

In the current Phase II study, elderly patients with first relapsed or primary refractory diffuse large B-cell lymphoma and ineligible for stem-cell transplantation received a single dose of yttrium-90 ibritumomab tiuxetan. Patients had previously been treated with chemotherapy or chemotherapy plus rituximab. Those patients who had previously been treated with chemotherapy were further divided into a) patients in whom induction therapy had failed and b) patients who had relapsed after achieving a complete response.

The overall response rate was higher in patients who had previously received chemotherapy than those who had previously received chemotherapy plus rituximab (52.5% vs. 19%, respectively). The complete response/complete response unconfirmed rates were higher in patients who had previously received chemotherapy and either failed induction therapy or relapsed after achieving a complete response (24% and 39.5%, respectively) than those patients who had previously been treated with chemotherapy plus rituximab (12%). Median progression free and overall survival were also higher in patients who had previously received chemotherapy than those who had previously received chemotherapy plus rituximab.

Two patients died from thrombocytopenic cerebral bleeding following administration of therapy. Haematologic adverse events were mild to moderate in nature.

Author’s conclusions: ‘Yttrium-90 ibritumomab is active in patients with relapsed and refractory diffuse large B-cell lymphoma and its further evaluation in phase 3 studies is ongoing'.

Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/110/1/54

2007-06-12T05:46:00.000-07:00

Dasatinib shows promising clinical benefit in patients with chronic myelogenous leukaemia who have failed first-line imatinib

Researchers have reported that the oral dual BCR/ABL and family tyrosine kinase inhibitor, Sprycel® (dasatinib), achieves higher response rates compared with high-dose imatinib, in a Phase II study of patients with imatinib-resistant chronic-phase (CP) chronic myelogenous leukemia (CML), in a study published in the journal Blood this week.

Imatinib, which inhibits the BCR-ABL tyrosine kinase implicated in the pathophysiology of CML, is the therapy of choice for previously untreated chronic-phase CML, achieving complete cytogenetic remission in up to 80% of patients. However, most patients treated with imatinib usually harbor minimal residual disease that eventually leads to disease recurrence.

Dasatinib, is approximately 300 times more potent against BCR-ABL than imatinib, and is currently approved for the second-line treatment of imatinib-resistant CML. In this setting, dasatinib has been shown to induce complete cytogenetic remission in 75% of imatinib-intolerant patients and 40% of imatinib-resistant patients.

In the current study, patients with CP CML resistant to imatinib were randomized to receive 140 mg dasatinib or high-dose imatinib (800 mg). At 15 months, the proportion of patients with a complete haematological response was significantly higher in patients receiving dasatanib versus imatinib (93% vs. 82%, respectively; P = .034), which included complete cytogenetic responses (40% vs. 16%, respectively; P = .004). In addition, the proportion of patients with a major molecular response was significantly higher with dasatinib versus imatinib (16% versus 4%, respectively; P = 0.038). Treatment failure was lower and progression-free survival higher in patients receiving dasatinib versus imatinib (P < .001), although the duration of benefit is not known because of the brief follow-up period.

Superficial oedema and fluid retention were more common in patients receiving imatinib, and pleural effusion was more common with dasatinib. Grade 3 to 4 non-hematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib.

Author’s conclusions: ‘Dasatinib represents a safe and effective therapy for CP CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.’

Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/12/5143
NOTE: A preliminary study presented at ASCO this year suggested that dasatinib mayshow promising clinical benefit as first-line treatment of chronic-phase (CP) chronic myelogenous leukemia (CML) http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abstractID=31679

2007-06-09T01:29:00.000-07:00

A healthy lifestyle may improve survival after breast cancer diagnosis

American researchers have reported that physically active women who eat a high vegetable and fruit diet have improved survival regardless of obesity according to a study published this week in the Journal of Clinical Oncology.

The authors of this study followed about 1,500 women diagnosed and treated for early-stage breast cancer. The combination of eating ≥5 daily servings of vegetables and fruits plus taking regular exercise equivalent to walking 30 minutes/day per week was associated with a 44% increase in survival. In addition, there was no apparent effect of obesity on survival.

Author’s conclusions: A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables and fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.

Source: http://jco.ascopubs.org/cgi/content/abstract/25/17/2345

2007-06-07T01:59:00.000-07:00

Cisplatin superior to carboplatin for first-line treatment of non-small-cell lung cancer

Researchers have reported a higher response rate for cisplatin compared with carboplatin when used to treat non-small cell lung cancer (NSCLC) according to results presented in this month’s Journal of the National Cancer Institute.

Pooled data from nine clinical trials comparing cisplatin to carboplatin as first-line treatment of patients with stage IIIb-IV non-small-cell lung cancer were analysed. The author’s found a significantly higher objective response rate (ORR) with cisplatin versus carboplatin (30% versus 24%, respectively; P<.001). There was a trend towards increased survival in patients receiving cisplatin, compared with those patients receiving carboplatin. In addition, cisplatin was more effective in prolonging survival in cases treated with third-generation regimens and in those with non-squamous histology.

Author’s conclusions: ‘Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.

Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity, wherease severe thrombocytopenia was more frequent during carboplatin-based chemotherapy.

Source: http://jnci.oxfordjournals.org/cgi/content/abstract/99/11/847

2007-06-06T01:49:00.000-07:00

Increased coffee consumption may reduce the risk of liver cancer

Swedish researchers have reported that an increase in consumption of 2 cups of
coffee per day is associated with a reduced risk of liver cancer, in a study reported in May’s issue of the journal Gastroenterology.

The authors, Drs Susanna Larsson and Alicja Wolk, pooled data in a meta-analysis of nine clinical studies (5 cohort and 4 case-control studies) involving 2,260 cases and 239,146 non-cases.

They found an inverse association between coffee consumption and risk of liver cancer that was statistically significant in 6/9 studies. The authors reported that an increase in coffee consumption of 2 cups per day was association with 43% reduction in risk of liver cancer.

The authors note several lines of evidence that a protective effect of coffee consumption on liver is biologically plausible. For example, coffee contains antioxidants such as chlorogenic acids, and animal studies have shown an inhibitory effect of coffee and chlorogenic acids on liver cancer

Author’s conclusions ‘Findings from this meta-analysis indicate
that coffee consumption may reduce the risk of liver cancer. The mechanisms involved and the substances in coffee that may be responsible for the relation remain to be elucidated.’

Source: http://www.gastrojournal.org/article/PIIS0016508507005689/abstract

2007-06-04T23:11:00.000-07:00

Sorafenib improves survival in advancer liver cancer

Researchers have found that sorafenib (Nexavar®) increases survival in patients with advanced hepatocellular carcinoma (HCC), in a study presented at this years' American Society of Clinical Oncology meeting in Chicago.

Sorafenib is a multi-kinase inhibitor that targets several tyrosine kinases and serine/threonine kinases involved in tumor cell proliferation and angiogenesis.

Sorafenib, is currently approved in the United States for treating approved for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy

In this Phase III trial, 602 patients with advanced HCC received sorafenib or placebo. Sorafenib significantly increased overall survival by 44%, compared with those patients receiving placebo (p=0.0006). The incidence of adverse side effects was similar between the two groups (52% percent in the sorafenib group and 54% for placebo). Patients who received sorafenib lived a median of 10.7 months compared with 7.9 months for those who received a placebo. Time to cancer progression was also significantly longer with sorafenib vs. placebo (5.5 vs. 2.8 months). Due to these positive findings, the study was terminated early.

Author’s conclusions ‘Sorafenib was well tolerated and is the first agent to demonstrate a statistically significant improvement in overall survival for pts with advanced HCC. This effect is clinically meaningful and establishes sorafenib as first-line treatment for these patients.

2007-06-04T07:56:00.000-07:00

Temsirolimus (Torisel) approved by the FDA for the treatment of advanced renal cell carcinoma

Approval was based on data published in The New England Journal of Medicine last week (http://scienceweekly.blogspot.com/2007_05_01_archive.html).

In the US, renal cell carcinoma is diagnosed in approximately 51,000 people per year and accounts for about 85 percent of all U.S. adult kidney cancer. Torisel is manufactured by Wyeth Pharmaceuticals, Inc.

Source: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01644.html

2007-06-04T02:47:00.001-07:00

Adjuvant interferon prolongs relapse-free survival in advanced melanoma

European researchers have reported that long-term adjuvant therapy with pegylated interferon-alpha2b (PEG-IFN; INTRON® A) improves relapse-free survival, compared with observation alone, in results presented at the American Society of Clinical Oncology meeting in Chicago this week.

In this Phase III study, patients with stage III melanoma received PEG-IFN for up to 5 years or were clinically observed during the study. Relapse-free survival (RFS) was significantly higher with PEG-IFN (34.8 months) versus clinical observation (25.5 months) over the 5 years of the study.

There was no significant difference between the study arms in either distant metastasis-free survival (DMFS) or overall survival (OS) in the entire population. However, patients with only microscopic nodal involvement (sentinel node-positive) seemed to have better outcomes, in terms of both RFS and DMFS.

Author’s conclusions: ‘Long term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. Patients with only microscopic nodal involvement (sentinel node positive) seemed to have greater benefit in terms of both RFS and DMFS. Similar better effects of adjuvant IFN therapy in pts with lower disease burden are observed in 2 consecutive EORTC trials (18952 and 18991) involving 2644 pts.’

Source: http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abstractID=32118

2007-06-03T14:40:00.000-07:00

Ginseng may reduce cancer-related fatigue

Researchers have reported that the herb ginseng may reduce cancer-related fatigue, in a study presented at this years’ American Society of Clinical Oncology meeting in Chicago.

In the current study, patients with a life expectancy of at least 6 months and a history of cancer-related fatigue for at least the previous month took either placebo, ginseng 750 mg/day, ginseng 1,000 mg/day or ginseng 2,000 mg/day for eight weeks.

Patients taking ginseng 1,000 mg/day or 2,000 mg/day acheived greated reductions in fatigue, than those patients taking ginseng 750 mg/day or placebo. Twenty-five percent of patients taking ginseng 1,000 mg/day and 27% of patients taking ginseng 2,000 mg/day reported that their fatigue levels were moderately better or much better, compared with 10% of patients taking ginseng 750 mg/day and 10% of patients taking placebo.

Author’s conclusions: ‘This randomized pilot trial provided data to suggest that American Ginseng doses of 1000-2000 mg/d may be effective for alleviating cancer related fatigue. Therefore, further study of American Ginseng in cancer survivors appears warranted.’

2007-06-03T00:51:00.000-07:00

Arsenic trioxide improves survival in acute promyelocytic leukemia

Researchers have reported that adding arsenic trioxide to stand therapy significantly improves survival in adults with newly diagnosed acute promyelocytic leukemia (APL), in a study presented at the American Society of Clinical Oncology meeting, in Chicago today.

Standard treatment for APL involves three phases of treatment known as induction, consolidation and maintenance therapy.

In this multi-centre, Phase III study, patients received standard consolidation therapy plus two courses of arsenic trioxide therapy or standard consolidation therapy alone. At 3 years, event-free survival was significantly higher in the standard consolidation therapy plus arsenic trioxide arm (77%), compared with the standard consolidation therapy arm (59%).

Author’s conclusions ‘The addition of 2 courses of arsenic trioxide consolidation following remission induction significantly improves survival’

2007-06-02T07:40:00.000-07:00

First-line cetuximab plus chemotherapy prolongs survival in head and neck cancer

European researchers have reported that adding cetuximab to a first-line chemotherapy regimen that includes cisplatin or carboplatn significantly prolongs survival in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) in data presented at this years’ American Society of Clinical Oncology Meeting in Chicago.

In this Phase III study, patients received cetuximab plus cisplatin or carboplatin and 5-fluoruracil (cetuximab group), or cisplatin or carboplatin plus 5-fluoruracil (control group). Median overall survival was significantly longer in the cetuximab group, compared with the control group (10.1 months vs. 7.4 months).

Author’s conclusions: ‘The addition of cetuximab to standard chemotherapy results in a clinically meaningful survival benefit. The observed median survival time of 10.1 months is among the longest ever reported in a phase III trial for these patients. Analysis of secondary endpoints is ongoing.’

Source: to be provided when available

2007-06-01T12:55:00.000-07:00

Cetuximab shows promising activity in advanced squamous cell carcinoma of the head and neck

European investigators have reported that single-agent cetuximab (Erbitux) shows promising activity and tolerability in patients with advanced squamous cell carcinoma of the head and neck (SCCHN), in results published in the Journal of Clinical Oncology.

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR) on tumour cells and impairs tumour cell growth and proliferation.

In this Phase II study, patients with advanced SCCHN and disease progression after platinum-based chemotherapy received single-agent cetuximab (single-agent phase). If patients experienced further disease progression, they received cetuximab in combination with platinum-based chemotherapy (combination therapy phase).

In the single-agent phase, the overall response rate (ORR) was 13%, disease control rate (DCR) was 46% and median time-to-progression (TTP) was 70 days. In the combination therapy phase, the ORR was 0%, DCR ws 26% and TTP was 50 days. Median overall survival was 178 days. Treatment was generally well tolerated.

Author’s conclusions ‘Single-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.’

Source: http://jco.ascopubs.org/cgi/content/abstract/25/16/2171

2007-06-01T05:21:00.000-07:00

Genetic test accurately predicts for gefitinib sensitivity in non-small cell lung cancer

American researchers have reported that use of a test to detect amplification of the epidermal growth factor receptor (EGFR) gene predicts sensitivity to gefitinib (IRESSA) in advanced non-small-cell lung cancer (NSCLC), in a study published in the Journal of Clinical Oncology.

Gefitinib was the first in a new class of anti-cancer drugs known as EGFR-tyrosine kinase inhibitors, which target the EGFR on tumour cells, a molecule involved in cellular processes involved in the promotion of tumor growth.

In this prospective study of 42 advanced NSCLC patients, amplification of the EGFR gene as determined by EGFR-FISH analysis in tumour samples (EGFR-FISH positivity) was associated with a significantly higher response rate and longer time-to-progression, compared with no amplication of the EGFR gene (EGFR-FISH negativity). However, the follow-up time was too short to allow for testing any differences in survival between treatment groups.

Author's conclusions: 'Gefitinib is active and well tolerated in patients with trial characteristics, and EGFR FISH analysis is an accurate predictor for such therapy.'

Source: http://jco.ascopubs.org/cgi/content/abstract/25/16/2248

Note: Following disappointing Phase III data in advanced NSCLC AstraZeneca voluntarily withdrew the European submission for IRESSA and regulatory authorities in the USA and Canada limited the use of IRESSA to those patients already experiencing benefit from the drug (see http://www.iressa.com/iressaHCP/9898_12838_0_0_0.aspx?mid=27)

2007-05-31T04:30:00.000-07:00

First-line temsirolimus improves survival in advanced renal cell carcinoma

American researchers have reported increased survival with temsirolimus (Torisel) compared with the standard treatment for this disease, interferon alpha, in patients with advanced renal cell carcinoma (RCC), in a study published today in The New England Journal of Medicine.

In this multicenter, phase III trial, 626 patients with previously untreated, advanced RCC received either temsirolimus, interferon alpha, or both as combination therapy.

Overall survival and progression-free were significantly longer in patients receiving temsirolimus, compared with patients receiving interferon alone. There was no significant difference in overall survival between patients in the interferon group versus the combination therapy group. In addition, there were significantly fewer serious adverse events in the tesirolimus group versus the interferon alpha group.

Author’s conclusions: ‘As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival.’

Note: Wyeth filed an application with the U.S. Food and Drug Administration in November 2006 for approval to market temsirolimus for the treatment of advanced renal cell carcinoma. A decision is expected shortly (July 2007).

Source: http://content.nejm.org/cgi/content/short/356/22/2271

2007-05-30T09:31:00.000-07:00

No benefits for clodronate in prostate cancer

UK researchers have reported no benefits with the bisphosphonate, clodronate, in non-metastatic prostate cancer in terms of overall or bone-metastasis-free surivival, in a study published today in the Journal of the National Cancer Institute.

In this randomized–controlled trial, there was no significant difference in bone-metastases-free survival or overall survival between clodronate or placebo over 10 years in men with nonmetastatic prostate cancer who were at high risk of developing bone metastases.

This study was initiated because of evidence suggesting that adjuvant bisphosphonates may reduce the rate of development of bone metastases-negative breast cancer, but it was not known whether they had similar effects in prostate cancer.

Author’s conclusions: ‘adjuvant sodium clodronate does not modify the natural history of nonmetastatic prostate cancer’.

Source: http://jnci.oxfordjournals.org/cgi/content/full/99/10/765

2007-05-29T14:52:00.001-07:00

Internet monitoring by Pharma companies

GlaxoSmithKline, Pfizer, and Johnson & Johnson are considering the use of proprietary computer software to monitor blogs, news groups, and patient online forums for mention of the companies' pharmaceutical products in internet postings. Please see Tom's blog for further detail.

Source: http://www.drug-injury.com/druginjurycom/2005/06/drug_manufactur.html#comments

2007-05-29T05:52:00.001-07:00

Controversy over the cardiovascular risks of Avandia for Type 2 diabetes

A controversial study reporting that rosiglitazone (Avandia) increases the risk of a myocardial infarction and death from cardiovascular disease was published last week in the journal The New England Journal of Medicine.

In this study, the authors combined the results from 42 randomized-controlled clinical trials. Each study had to last for more than six months, include a control group other than Avandia, and include outcomes data on data myocardial infactions and deaths from cardiovascular disease. The authors reported that Avandia increased the risk of a myocardial infarction by 43% and the risk of death from cardiovascular causes by 64%.

The authors noted that this study had several limitations: 1) results were pooled from trials that were not intended to explore cardiovascular outcomes, 2) definitions of a myocardial infarction were not available, 3) many of the trials were small and of short duration, and as a result there were few adverse cardiovascular events or deaths. As a result, getting to the nittry gritty statistical stuff (switch off now if you want to), the confidence intervals for the odds ratios were wide, causing uncertainty on the magnitude of the harmful effect of Avandia.

Not surprisingly, GSK shares plummeted by 8% on the day that this paper was released on-line. But, GSK’s problems didn’t stop there. The FDA released safety alert for Avandia and advised patients who take it to consult their doctors (http://www.fda.gov/bbs/topics/NEWS/2007/NEW01636.html). In this report, the FDA mention that GSK provided them with a meta-analysis of 42 studies, which according to the FDA ‘suggested that patients receiving short-term treatment with Avandia may have a 30-40 percent greater risk of heart attack and other heart-related adverse events than patients treated with placebo or other anti-diabetic therapy.’

Even worse, the medical director at GSK, has reported that 4,450 patients enrolled in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial, which aims to evaluate the long-term risk of Avandia and other rosiglitazones, have dropped out this week because of these safety concerns.(http://www.nytimes.com/2007/05/26/business/26drug.html). This could result in the trial being stopped early if the target number of patients cannot be reached. This could mean trouble for GSK as the results of this study, if they are positive, would have helped to allay any fears regarding Avandia.

Finally, I note with some amusement that the lead author on the study, Dr Nissen, discloses his affiliation with several pharmaceutical companies, some of whom have competitor products to Avandia, notably Eli-Lilly and Takeda who produce Actos (pioglitazone) also for type 2 diabetes (see the disclosure stament from Dr Nissen below). One has to wonder whether any inherent bias has creeped into this meta-analysis when Dr Nissen was performing his review of the clinical trials. Perhaps it should have been performed by an independent body?

‘Dr. Nissen reports receiving research support to perform clinical trials through the Cleveland Clinic Cardiovascular Coordinating Center from Pfizer, AstraZeneca, Daiichi Sankyo, Roche, Takeda, Sanofi-Aventis, and Eli Lilly. Dr. Nissen consults for many pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. No other potential conflict of interest relevant to this article was reported.‘

Source: http://content.nejm.org/cgi/content/full/NEJMoa072761

2007-05-28T13:23:00.000-07:00

Calcium and Vitamin D associated with lower risk of breast cancer in pre-menopausal women

American scientists have found that women who consume higher amounts of calcium and vitamin D may have a lower risk of developing premenopausal breast cancer, in research published in the journal Archives of Internal Medicine.

In this study, researchers prospectively evaluated calcium and vitamin D intake and breast cancer incidence among approximately 11,000 premenopausal and approximately 21,000 postmenopausal women 45 years or older who were free of cancer and cardiovascular disease at the start of the study.

Over an average of 10 years, higher intakes of total calcium and vitamin D were moderately associated with a lower risk of breast cancer in premenopausal women.

Author’s conclusions: ‘Higher intakes of calcium and vitamin D may be associated with a lower risk of developing premenopausal breast cancer.’

2007-05-27T10:03:00.000-07:00

No association between regular multivitamin use and risk of prostate cancer, but increased risk with excessive use

American researchers have found no association between regular multivitamin use (up to seven times per week) and risk of prostate cancer. However, they did find an association between excessive multivitamin use (more than seven times a week) and risk of prostate cancer. The positive association between excessive multivitamin use and risk of prostate cancer were strongest in men with a family history of prostate cancer or who were also taking individual selenium, beta-carotene, or zinc supplements.

Authors conclusions ‘Regular multivitamin use is not associated with the risk of early or localized prostate cancer. The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation.’

Source: http://jnci.oxfordjournals.org/cgi/content/full/99/10/754#TBL5

2007-05-26T01:33:00.000-07:00

Eltrombopag, being developed by GSK for thrombocytopenia, demonstrates encouraging Phase I results

Eltrombopag is the first in a new class of oral, small-molecule, non-peptide agonist of the thrombopoietin receptor, being developed by GSK for the treatment of thrombocytopenia (low platelet count) due to various causes. Results published in the journal Blood suggest that suggest that the pharmacodynamic, pharmacokinetic, and safety profile of eltrombopag supports further investigation in Phase II trials.

In this Phase I placebo-controlled trial, eltrombopag was given to 73 healthy male volunteers as once-daily oral capsules for 10 days at doses ranging from 5 to 75 mg. Increases in platelet counts were seen at 30, 50 and 75 mg doses of eltrombopag, and started rising at Day 5 of treatment and peaking on Day 15. The pharmacokinetics of eltrombopag were dose dependent and linear, and platelet counts increased in a dose-dependent manner. There were no apparent differences in the incidence of adverse events between volunteers in the eltrombopag or placebo groups.

The authors conclude ‘These observations indicate that eltrombopag is a once-daily, oral Thrombopoietin receptor agonist with demonstrated thrombopoietic activity in human subjects, encouraging further studies in patients with thrombocytopenia.’

Source: http://bloodjournal.hematologylibrary.org/

NOTE: GSK seem to be investigating the use of Eltrombopag in various indications, including patients with idiopathic thrombocytopenic purpura and patients with low platelet counts who are receiving chemotherapy with Adriamycin and Ifosfamide.

2007-05-25T00:05:00.000-07:00

Some Cancers Linked To Very Low Frequency Electromagnetic Fields

Some cancers, notably myeloid leukemia and Hodgkin’s lymphoma, could be linked to extremely low frequency electromagnetic fields, suggests research published in the journal of Occupational and Environmental Medicine.

In this study, researchers, retrospectively checked the records of 20,141 retired or employed Swiss railway workers between 1972 and 2002. They reported no link between electromagnetic field exposure and deaths from lymphoid leukaemia, non-Hodgkin's lymphoma and brain tumours. However, there was some evidence that higher levels of electromagnetic field exposure increased the rates of myeloid leukaemia and Hodgkin's lymphoma. Drivers were more than four times as likely to die of myeloid leukaemia, and over three times as likely to die of Hodgkin's lymphoma, as station masters.

The authors conclude ‘We found some evidence of an exposure-response association for myeloid leukaemia and Hodgkin's disease, but not for other haematopoietic and lymphatic malignancies and brain tumours’.

Source: http://oem.bmj.com/cgi/content/abstract/oem.2006.030270v1

2007-05-24T09:57:00.001-07:00

Liquid-based cytology just as sensitive as conventional cytology in cervical cancer screening

Despite falling incidence, cervical cancer remains the tenth leading cause of cancer death. However, cervical screening programmes have been shown to reduce the incidence of this type of cancer.

Liquid based cytology (LBC) is a new way of preparing cervical samples for examination in the laboratory, which involves scraping the sample into a vial of liquid, compared with conventional cytology were the sample is scraped onto a miscroscope slide. In both instances, the prepared sample is examined under a microscope with the aim of detecting any malignant cells. Previous studies comparing the accuracy of both of these techniques have produced conflicting results.
In this study of approximately 45, 0000 women in Italy, the authors reported no significant difference in diagnostic sensitivity between LBC and conventional cytology.

The authors conclude that although there is no difference is sensitivity between the two techniques, the main advantage of LBC is that it reduces the number of unsatisfactory slides that are usually difficult to interpret.

Source: http://www.bmj.com/cgi/rapidpdf/bmj.39196.740995.BEv1

2007-05-24T08:26:00.000-07:00

Physicians competent in colonoscopies after performing 150 procedures

Colonoscopies are considered the gold standard for detecting colon cancer, the second leading cause of cancer deaths in the United States. Research presented this week at Digestive Disease Week 2007 (DDW) reported that for a physician to be competent in colonoscopy they have to complete more than 150 procedures.

In this study of colonoscopies performed by 24 first-year fellows in 15 centres, the success rate was determined by the completion rate and the cecal intubation time (the time to insert a tube into the first part of the bowel). The success rate was significantly improved and reached the competency standard after 150 procedures. For example, after 150 procedures the cecal intubation time decreased from 14.2 to 9 mins.