financial: HealthLinx (Australia - biomarker) health research company collapses into administration following termination of key funding deal

financial - HealthLinx

Friday, 10 May 2013 11:38

Yolanda Redrup

A publicly-listed Melbourne-based health diagnostic company conducting researching into ovarian cancer and a number of other serious diseases has collapsed following the termination of a key funding agreement.
HealthLinx, a biomarker and diagnostic development business, has been placed in administration with David Ross and Shanon Thomson from Hall and Chadwick appointed as administrators earlier this week.
On February 26, 2010, HealthLinx shares peaked on the ASX at $0.18, but the price has since declined gradually until the business entered a trading halt on April 30 this year.
At the time, the stocks were worth just $0.001.

The Rest of the Story About Hospital Pricing | The Health Care Blog

The Health Care Blog

Search of: "metformin ovarian" - List Results - ClinicalTrials.gov

Search results

Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

Abstract

"The use of the type 2 diabetics drug metformin has been correlated with enhanced progression-free survival in ovarian cancer. The literature has speculated that this enhancement is due to the high concentration of metformin directly causing cancer cell death. However, this explanation does not fit with clinical data reporting that the women exposed to constant micromolar concentrations of metformin, as present in the treatment of diabetes, respond better to chemotherapy. Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability. We demonstrate that previous exposure and maintenance of metformin in conjunction with carboplatin produces a synergistic enhancement in cytotoxicity of A2780 and SKOV3 cells (55% and 43%, respectively). Furthermore, in 5 (44%) of the 11 ovarian cancer primary cultures, micromolar metformin improved the cytotoxic response to carboplatin but not paclitaxel or doxorubicin. In conclusion, we present data that support the need for a clinical study to evaluate the adjuvant maintenance or prescription of currently approved doses of metformin during the chemotherapeutic treatment of ovarian cancer."

CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer

CA-125 

OBJECTIVE:

In the present study, we evaluated changes in CA-125 cut-off values predictive of complete interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) using receiver operating characteristic (ROC) analysis.

METHODS:

This retrospective single-institution study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer and a pre-NAC serum CA-125 level of greater than 40 U/mL who were treated with neoadjuvant platinum-based chemotherapy followed by IDS between 1994 and 2009. Logistic regression analysis was used to evaluate univariate and independent multivariate associations with the effect of clinical, pathological, and CA-125 parameters on complete IDS, and ROC analysis was used to determine potential cut-off values of CA-125 for prediction of the possibility of complete IDS.

RESULTS:

Seventy-five patients were identified. Complete IDS was achieved in 46 (61.3%) patients and non-complete IDS was observed 29 (38.7%). Median pre-NAC CA-125 level was 639 U/mL (range, 57 to 6,539 U/mL) in the complete IDS group and 1,427 U/mL (range, 45 to 10,989 U/mL) in the non-complete IDS group. Median pre-IDS CA-125 level was 15 U/mL (range, 2 to 60 U/mL) in the complete IDS group and 53 U/mL (range, 5 to 980 U/mL) in the non-complete IDS group (p<0.001). Multivariate analyses performed with complete IDS as the endpoint revealed only pre-IDS CA-125 as an independent predictor. The odds ratio of non-complete IDS was 10.861 when the pre-IDS CA-125 level was greater than 20 U/mL.

CONCLUSION:

The present data suggest that in the setting of IDS after platinum-based NAC for advanced ovarian cancer, a pre-IDS CA-125 level less than 20 U/mL is an independent predictor of complete IDS.

Reproductive factors for ovarian cancer in southern Chinese women

open access

Objective To investigate the association between reproductive factors and the risk of ovarian cancer among southern Chinese women.

Methods A hospital-based case-control study was undertaken in Guangzhou, Guangdong Province, between 2006 and 2008. A structured questionnaire was used to obtain information on parity, oral contraceptive use and other reproductive factors in a sample of 500 incident ovarian cancer patients and 500 controls (mean age, 59 years). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models.

Results High parity was inversely associated with ovarian cancer, with an adjusted OR 0.43 (95% CI, 0.30 to 0.62) for women who had given birth to 3 or more children compared to women who had given no more than one birth. Ever use of oral contraceptives was also protective against ovarian cancer; adjusted OR 0.56 (95% CI, 0.40 to 0.78). No association was found for hormone replacement therapy, menopausal status, hysterectomy and family history of ovarian and/or breast cancer.

Conclusion High parity and oral contraceptive use are associated with a lower risk of ovarian cancer in southern Chinese women.

INTRODUCTION

Ovarian cancer ranks as the seventh most common cause of cancer mortality among women [1], accounting for 4.2% of cancer deaths [2]. It is the eighth most common cancer in women, with approximately 225,000 new cases reported worldwide in 2008 [1]. The incidence of ovarian cancer varies geographically. The age-standardised rate (per 100,000 females) is only 3.8 in China, relatively lower than developed countries such the USA (8.8) and Australia (7.7) [1]. The majority of ovarian malignancies are epithelial in origin [3] and are often diagnosed in the advanced stages of the disease due to the subtle and non-specific symptoms [4]. There is currently no effective screening method available for the detection of this disease [5], which has an overall five-year survival rate of approximately 45% [6]..........

The role of cytoreductive surgery in advanced-stage ovarian cancer: a systematic review

Abstract

Updates Surg. 2013 May 8. [Epub ahead of print]

"It has already been proven that ovarian cancer is the sixth most common cancer among women, and it is considered the leading cause of death by gynecologic cancer in developed countries. This article is a literature review based on the use of cytoreductive surgery matched with adjuvant chemotherapy in advanced-stage ovarian cancer. According to the statistics, the difficulty of obtaining an early diagnosis results in a delay in the disease treatment and as a consequence, in many cases, ovarian cancer is still diagnosed in the advanced stage of the disease. Primary surgery is performed, in addition to diagnosis and staging, to achieve optimal cytoreduction. The purpose of this article is to review the different surgical approaches in the management of epithelial ovarian cancer, specifically the high-stage disease, with a special concentration on the most recent therapeutic additions to our current knowledge, such as hyperthermic intraperitoneal chemotherapy and new therapeutic drugs. Surgical treatment still plays a pivotal role in the management of advanced-stage ovarian cancer. Complete cytoreduction continues to be, when feasible, the objective to be attempted in the surgical treatment of advanced ovarian cancer. Obviously, the success of the operation depends on numerous factors, including patient selection, the locations of tumors, and surgeon expertise. To offer patients the best possible outcome with the least accompanying morbidity, strong consideration should be given to the referral of such patients to expert care centers for primary surgery, because it may be the best means currently available for improving overall survival."

CME: Differential Diagnosis and Clinical Relevance of Ovarian Carcinoma Subtypes: Abstract and Introduction

Blogger's Note: as always, Medscape requires registration (free) to vie; worth reading - as an example (eg. things you may or may not  know): "In addition, CCCs are not associated with BRCA abnormalities.^[32]"

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CME

From Expert Review of Obstetrics & Gynecology

Differential Diagnosis and Clinical Relevance of Ovarian Carcinoma Subtypes CME

Chris M.J. Conklin, MD; C. Blake Gilks, MD, FRCPC

Faculty and Disclosures

CME Released: 12/24/2012; Valid for credit through 12/24/2013

CME Information Earn CME Credit »

1. Abstract and Introduction
2. Serous Carcinomas
3. High-Grade Serous Carcinoma
4. Low-Grade Serous Carcinoma
5. Ovarian MCs
6. Ovarian ECs
7. CCCs of the Ovary
8. Conclusion
9. Expert Commentary
10. Five-Year View
11. Key Issues

• References

Abstract and Introduction

Abstract

The five main subtypes of ovarian surface epithelial carcinoma (high-grade serous, low-grade serous, endometrioid, clear cell and mucinous) are different diseases, with differences in genetic and environmental risk factors, precursor lesions, molecular events during oncogenesis, patterns of spread and response to treatment. With recent advances in surgical pathology, it is possible to reproducibly diagnose these subtypes in routine surgical pathology practice. This review examines these subtypes of ovarian carcinoma, focusing on differential diagnosis, molecular features and current treatment strategies. The increasing understanding of the molecular abnormalities associated with each subtype is leading to exploration and introduction of more subtype-specific treatment of ovarian carcinoma.

Introduction

Ovarian cancer is the seventh most commonly diagnosed female cancer worldwide, accounting for almost 4% of all female cancers.^[1,2] Furthermore, the proportion of ovarian cancer is increasing due to effective Papanicolaou smear screening programs, leading to reduced incidence of cervical cancer.^[3] Ovarian surface epithelial carcinomas are the most common malignant ovarian tumors, accounting for 90% of cases, and are the most lethal gynecological malignancies.^{[4,5]...........}

Incidence of Ovarian Carcinomas by Subtype. Approximately 96% of ovarian carcinomas can be diagnosed as one of these five subtypes (HGSC [71% of cases], MC [3.2%], EC [8.3%], CCC [9.5%], LGSC [4.1%]), which have distinct molecular abnormalities and behaviors. These frequencies are based on data from British Columbia, Canada. CCC: Clear cell carcinoma; EC: Endometrioid carcinoma; HGSC: High-grade serous carcinoma; LGSC: Low-grade serous carcinoma; MC: Mucinous carcinoma. Data taken from [36].

 

Hospital Billing Varies Widely -- But Quality Has Nothing To Do With It - Forbes

 Blogger's Note: this issue of costs/quality is all over the 'media' recently

Forbes

Phase I Dose-Escalation Study and Population Pharmacokinetic Analysis of Fixed Dose Rate Gemcitabine+Carboplatin as 2nd-Line Therapy Ovarian Cancer

abstract

Purchase $39.95

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Highlights

•

Study with weekly fixed dose rate gemcitabine plus carboplatin in ovarian carcinoma after first line therapy (28 day schedule).

•

Population pharmacokinetic modeling shows that increase of carboplatin dose requires decrease of fixed dose rate gemcitabine dose and vice versa.

•

Carboplatin plus fixed dose rate gemcitabine as a weekly schedule in ovarian carcinoma results in increased myelosuppression.

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Objective

This Phase I study of Fixed Dose Rate (FDR) gemcitabine and carboplatin assessed the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetic (PK)/pharmacodynamic (PD) profile and preliminary anti-tumor activity in patients with recurrent ovarian cancer (OC).

Methods

Patients with recurrent OC after first line treatment were treated with carboplatin and FDR gemcitabine (infusion speed 10 mg/m²/min) on days 1, 8 and 15, every 28 days. ....... Population pharmacokinetic modeling and simulation was performed for the further investigate the optimal schedule.

Results

Twenty three patients were enrolled. Initial dose escalation was performed using FDR gemcitabine 300 mg/m² (administered at infusion speed of 10 mg/m²/min) combined with carboplatin AUC 2.5 and 3. Excessive bone marrow toxicity led to a modified dose escalation schedule: carboplatin AUC 2 and dose escalation of FDR gemcitabine (300 mg/m², 450 mg/m², 600 mg/m² and 800 mg/m²). DLT criteria as defined per protocol prior to the study were not met with carboplatin AUC 2 in combination with FDR gemcitabine 300-800 mg/m² because of myelosuppressive dose-holds (especially thrombocytopenia and neutropenia).

Conclusions

FDR gemcitabine in combination with carboplatin administered in this 28 days schedule resulted in increased grade 3/4 toxicity compared to conventional 30-minute infused gemcitabine. A two weekly schedule (chemotherapy on day 1 and 8) would be more appropriate.

paywalled - Response to: Risk-reducing salpingectomy as a new and safe strategy to prevent ovarian cancer.

paywalled

Response to: Risk-reducing salpingectomy as a new and safe strategy to prevent ovarian cancer

Purchase $31.50

Refers To

• Risk-reducing salpingectomy as a new and safe strategy to prevent ovarian cancer
• American Journal of Obstetrics and Gynecology, Available online 9 May 2013,
• PDF (494 K)       

Case Reports - Complete resection of a giant ovarian tumor

Abstract

INTRODUCTION

Giant ovarian tumours are rare. Benign mucinous cyst adenomas account for about 15 % of all ovarian neoplasms and are among the largest known tumors. About 80% of mucinous tumours are benign , 10 % are borderline and 10 % are malignant . They are usually common between third to fifth decade of life . We present a case of giant ovarian mucinous cyst adenoma in an Indian woman weighing 56.95 kg or 125.29 lbs........

USF, Aetna to examine influence of genetic testing on breast cancer treatment

news

The University of South Florida (USF) and Aetna (NYSE: AET) are launching a ground-breaking study that will examine the influence genetic testing may have on clinical treatment decisions among breast cancer patients and their doctors. Understanding the connection between genetic risk factors, treatment options and results can guide policies and services that can help patients and doctors make more informed, personalized decisions that lead to better health.
The National Institutes of Health (NIH) awarded funding to USF for the five-year American BRCA Outcomes Among the Recently Diagnosed (ABOARD) study. The study will follow 5,000 Aetna members from across the country who have been newly diagnosed with breast cancer and who are undergoing genetic testing.........

"The new study builds on an existing research partnership between this multidisciplinary team and researchers from the American Cancer Society. The groups have been working together for the past two years, with support from the Aetna Foundation, to better understand the experiences of individuals who have had genetic tests to determine their inherited risk of cancer. The study also looked at differences in treatment, information and health outcomes among minority patients. Results are expected to be published later this year."

Study Suggests Benefit for Salpingectomy

Medpage news

NEW ORLEANS -- Offering women bilateral salpingectomy with preservation of ovaries as part of hysterectomy may reduce their risk of developing adnexal masses, researchers reported here.
In a single center study, the bilateral salpingectomy rates rose from 2.9% in 2009 and 2010, to 26% in 2011, when the center began offering bilateral salpingectomy to all women undergoing hysterectomy with ovary preservation. The salpingectomy rate jumped to 73% in the first 6 months of 2012, Susan K. Park, MD, of Olive View-UCLA Medical Center and colleagues, reported at the American Congress of Obstetricians and Gynecologists meeting...........

Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status

Abstract

OBJECTIVE:

To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression.

METHODS:

We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry.

RESULTS:

Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01).

CONCLUSION:

Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression.

Patient navigation in the oncology care setting

Abstract

OBJECTIVES:

To review the evolution and current status of patient navigation in cancer care settings, discuss challenges as navigation evolves, and suggest education and research needs to optimize outcomes associated with navigation processes and nurse navigator roles.

DATA SOURCES:

Literature review, association publications, and government and non-governmental documents.

CONCLUSION:

Since its inception over two decades ago, navigation programs have been established in hospitals in the United States, Canada, Australia, and other nations. Despite wide-spread implementation, challenges remain in defining the navigator processes and navigator roles, preparation, qualifications, and job descriptions. Scientific efforts are needed to craft and codify these definitions.

IMPLICATIONS FOR NURSING PRACTICE:

Nurses and organized nursing must identify the needs reflected by the navigation processes and support role delineation, identification, and validation of educational curriculum and competencies.

Patients’ and oncologists’ views on the treatment and care of advanced ovarian cancer in the UK: results from the ADVOCATE study

Abstract
 

Background:

Most patients presenting with advanced ovarian cancer (AOC) eventually relapse. Symptom palliation, maintenance of quality of life (QoL) and prolongation of life are primary therapeutic goals.

Methods:

Sixty-six UK oncologists completed an online survey about AOC management. Two hundred and two patients were interviewed about care, treatment experiences and expectations.

Results:

Prior to diagnosis, 34% (69 out of 202) of women had 3 symptoms associated with AOC. Twenty-one per cent (43 out of 202) thought poor symptom recognition by general practitioners (GPs) delayed diagnosis. Amelioration of side effects experienced was variable, for example, only 54% (68 out of 127) distressed by alopecia had received sufficient information about it. Clinicians were asked ‘What minimum gain in progression-free survival (PFS) would make you feel it worthwhile to offer maintenance therapy?’; 48% (24 out of 50) indicated 5–6 months, but 52% (26 out of 50) believed patients would find PFS of 3–4 months acceptable. When patients were presented with hypothetical scenarios, 33% (52 out of 160) would require 1–2 months extra life, 6% (10 out of 160) 3–4 months, 31% (49 out of 160) 5–6 months, and 31% (49 out of 160) 7 months. However, 86% (173 out of 202) would accept treatment that improved QoL without prolongation of life. When asked what was most important, 33% (67 out of 201) said QoL, 9% (19 out of 201) length of life and 57% (115 out of 201) said both were equally important.

Conclusion:

Clinicians’ and patients’ experiences, expectations and priorities about OC management may differ.

Etiology and significance of incidentally detected focal colonic uptake on FDG PET/CT/+Blogger's Opinion

Blogger's Note/Opinion:  of interest to Lynch Syndrome patients; this also may suggest further research/opinion requirements in Western populations and is it really epidemiology (?) - questions, of course (as a one-person example of this study's results)

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open access

Background: Incidental colonic uptake of 18F-flurodeoxyglucose (FDG) is not an infrequent finding encountered during whole body positron emission tomography (PET) imaging. Almost all studies on this topic are in Western populations, which have a markedly different epidemiological profile for colorectal premalignant and malignant conditions as compared to that of the Indian subcontinent.  

Aim: The purpose of this study was to assess the etiology of incidentally detected focal FDG uptake in the colon by comparing it with colonoscopy and histopathology.

Conclusions:

Our study shows that a significant proportion of patients (62.5%, 20/32) showing an incidental focal FDG uptake will harbor premalignant (adenomatous polyps) or malignant lesions, and further evaluation with colonoscopy and biopsy is warranted in such cases.

Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours : British Journal of Cancer

Abstract

Background:

Microsatellite instability (MSI) is a molecular phenotype due to defective DNA mismatch repair (MMR) system. It is used to predict outcome of colorectal tumours and to screen tumours for Lynch syndrome (LS). A pentaplex panel composed of five mononucleotide markers has been largely recommended for determination of the MSI status. However, its sensitivity may be taken in default in occasional situations. The aim of the study was to optimise this panel for the detection of MSI.

May Index: Seminars in Oncology Nursing: Patient Navigation in Cancer Care

Abstracts (index)

Legal services: a necessary component of patient navigation

Abstract 

Semin Oncol Nurs.

OBJECTIVES:

Access to legal advocacy is an essential tool to help cancer patients and survivors through the continuum of care. This article examines delivery models that can seamlessly integrate into patient navigation programs.

DATA SOURCES:

Technical reports, books, journal articles, and Web sites.

CONCLUSION:

Psychosocial obstacles are common barriers of low-income individuals facing a cancer diagnosis. Legal solutions can help to minimize these obstacles, yet patients rarely have access to these services. Training patient navigators to appropriately screen for legal issues and collaborate with attorneys can be used to help prevent, rather than just react to, legal issues by addressing them as a part of a treatment plan.

IMPLICATIONS FOR NURSING PRACTICE:

Attorneys working with patient navigators, particularly nurse navigators, can impact oncology nursing practice by providing an innovative collaboration that is consistent with emerging trends in patient-centered treatment.

conference notice: AICR Food, Nutrition, Physical Activity and Cancer Nov 2013

 2013 AICR Research Conference

 

Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial

open access

Participants 1006 healthy women aged 45-58 who were recently
postmenopausal or had perimenopausal symptoms in combination with
recorded postmenopausal serum follicle stimulating hormone values.
502 women were randomly allocated to receive hormone replacement
therapy and 504 to receive no treatment (control). Women who had
undergone hysterectomy were included if they were aged 45-52 and
had recorded values for postmenopausal serum follicle stimulating
hormone.

DiscussionIn this randomised trial including 1006 women we found a
significantly decreased risk of the composite endpoint of death,
heart failure, or myocardial infarction when hormone
replacement therapy was started early in postmenopause. The
beneficial effect occurred in the 10 years randomisation phase
and was maintained for an additional six years of
non-randomised follow-up.........

Conclusions
After 10 years of randomised treatment, women receiving
hormone replacement therapy early after menopause had a significantly
reduced risk of mortality, heart failure, or myocardial infarction, withoutany apparent increase in risk of cancer, venous thromboembolism, or
stroke.

".....When the first results from the Women’s Health Initiative were
reported in 2002, the Danish Osteoporosis Prevention Study
intervention (randomisation phase) was stopped because of a
reported excess risk of breast cancer and adverse cardiovascular
events.11 The discrepancy between that trial and the Danish
Osteoporosis Prevention Study may be explained by a difference
in medication or in the characteristics of women included in the
trials........

Trial registration ClinicalTrials.gov NCT00252408.

Grapefruit–drug interactions (NICE) - research article/commentary/ilist of drug interactions including statins)

Issue 48 – April 2013


Research:  Overview: A pharmacokinetic interaction between grapefruit and certain drugs was first identified over 20 years ago. To date, more than 85 drugs have the possibility of interacting with grapefruit, many of which are widely prescribed for important or common medical conditions. The main interaction results from interference in the activity of the cytochrome P450 3A4 (CYP3A4) enzyme..........

 
Commentary:
"This review provides a comprehensive background to the pharmacokinetics of grapefruit-drug interactions. Of particular importance is the table listing the drugs with the potential to interact with grapefruit – a list that is wider than one may suspect. Also of interest to practitioners is the information on the amount of grapefruit that could cause a clinically significant effect and that all forms of grapefruit have the potential to cause the interaction.
"The true extent of grapefruit-drug interactions in clinical practice is not clear, and this review is not able to provide such data. Under-reporting of such interactions via adverse drug reaction reporting to the MHRA in day-to-day clinical practice is likely and the yellow card system provides a straightforward mechanism for reporting any suspected events."

Direct Healthcare Professional Communication on the risk of haematologic second primary malignancies in patients treated with thalidomide

08 April 2013

Direct Healthcare Professional Communication on the risk of haematologic second primary malignancies in patients treated with thalidomide

Dear Healthcare Professional:
Celgene Europe Limited would like to inform you of the following:

Summary

 A statistically significant increase in the risk of haematologic second primary malignancies (acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS)) has been observed in an ongoing study in patients with previously untreated multiple myeloma receiving melphalan, prednisone, and thalidomide, compared with patients treated with lenalidomide plus dexamethasone.

 The risk of haematologic second primary malignancies with thalidomide increased over time, to approximately 2% after 2 years and 4% after 3 years.

 Before starting thalidomide treatment in combination with melphalan and prednisone, take into account both the benefit achieved with thalidomide and the risk of acute myeloid leukaemia and myelodysplastic syndromes.

 Carefully evaluate patients before and during treatment using standard cancer screening and provide appropriate treatment..........