Increasing OC rates call for more research

According to the American Cancer Society, oral cancer (OC) has increased by 21 per cent in the last five years, while new cancers of all types have risen by 8 per cent. Tongue squamous cell carcinoma (TSCC) is one of the most common types of OC and has increased by more than 37 per cent in this period. Although overall cancer deaths decreased during this period, those due to OC increased by 4 per cent and those due to TSCC by 10 per cent. According to Cancer Research UK, while female OC rates have remained significantly lower than male rates, incidence trends have been similar, with an average increase of 3 per cent each year since 1989. It is well documented that this increase in OC is largely due to lifestyle, with smoking and heavy alcohol consumption significantly increasing the risk of an individual developing the disease.

However, new research by scientists at the University of Illinois at Chicago (UIC) may help in the fight against this ever-increasing cancer. According to the researchers, the spread of cancer cells in the tongue may be reduced if a gene that regulates cancer cell migration can be controlled. Dr Xiaofeng Zhou, assistant professor in the UIC Center for Molecular Biology of Oral Diseases, led the study and believes that OC is an under-treated and poorly-understood disease, noting that improvements in patient survival require better understanding of tumour invasion and how the cancer spreads.

The study, which was published in the 1st August issue of the International Journal of Cancer (2010;127:505-512), examined a non-coding gene, called miR-138, and demonstrated that a reduced level of it is associated with enhanced ability of TSCC cells to spread. Previously, the same team reported that reduced miR-138 level is correlated with enhanced metastatic potential in TSCC cells. In the current study, it was demonstrated that miR-138 suppresses TSCC cell migration and invasion by regulating two key genes in the Rho GTPase signalling pathway, RhoC and ROCK2. The scientists believe that miR-138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease.

Further, Case Western Reserve University School of Dental Medicine researchers recently discovered a biomarker, called human beta defensin-3, which may serve as an early warning to OC. The defensin is present in all OCs and associated with the early stages of the disease. It is thought that using the biomarker to detect OC holds potential for saving lives when the cancer is most curable.

The increasing prevalence of OC highlights the need for more work like this to be conducted. Research such as that carried out by UIC and Case Western may mean that aggressive tumours can be detected early and targeted therapies can eventually be developed in the fight against this disease.

Alice Rossiter
Editor, Cancer Drug News

Shares tumble as trials fail

Several Phase II and III trials have recently produced disappointing data, resulting in the failure to meet primary and secondary endpoints. The impact of this can be huge for some of the smaller companies, causing share prices to drop considerably.

Of particular note, Curis, Roche and Genentech's Phase II trial of GDC-0449, a first-in-class Hedgehog pathway inhibitor, tested in combination with Avastin (bevacizumab) and FOLFOX or FOLFIRI chemotherapy in first-line metastatic colorectal cancer (MCRC) patients did not meet its primary endpoint of extending the time from randomisation to disease progression or death when compared to patients who received only the current standard-of-care treatment. As a result, Curis' share price sank by 48 per cent, whereas the company's stock had more than doubled during the past year until this point. Despite these disappointing results in MCRC, Curis remains encouraged that the clinical development of GDC-0449 in other cancers continues to make good progress.

Further disappointment arose for Bayer HealthCare and Onyx Pharmaceuticals, when a final analysis of the Phase III NExUS trial evaluating Nexavar (sorafenib) in patients with advanced non-squamous non-small cell lung cancer (NSCLC) showed that the study did not meet its primary endpoint of improving overall survival (OS) in the first-line setting, although a positive secondary endpoint of progression-free survival (PFS) was observed. The two companies are to further review the findings of this analysis to determine what, if any, impact these data might have on other ongoing clinical trials evaluating the safety and efficacy of sorafenib.

Marshall Edwards (Novogen) recently experienced a similar blow, when a final analysis of the company's Phase III OVATURE trial of orally-administered phenoxodiol in women with recurrent ovarian cancer determined that the study did not show a statistically significant improvement in its primary (PFS) or secondary (OS) endpoints. Following this news, the company's share price dropped by 50 per cent.

Also, in May, GTx reported top-line results of a Phase III trial evaluating toremifene 20mg for the prevention of prostate cancer (PCA) in men with high-grade prostatic intraepithelial neoplasia, which showed that the incidence of PCA was lower in men receiving the drug compared to placebo, but not statistically significantly different (p=0.385). A 10.2 per cent relative risk reduction at three years was observed. Following these results, the company's share price dropped by over 33 per cent. Dr Mitchell S Steiner, CEO of GTx, commented: "We designed the Phase III trial based upon the successful outcome of our Phase IIb clinical trial. Toremifene 20mg did also reduce prostate cancer in our Phase III study, but based on our review of the top-line data, there is not a sufficient reduction in cancers compared to placebo over a three-year period to demonstrate the statistical significance required for this study."

Alice Rossiter
Editor, Cancer Drug News

Potential miRNA drug target identified for mesothelioma

Although mesothelioma is generally regarded to be a rare cancer, it appears to be getting more common. More than 2,300 people are diagnosed with the disease every year in the UK alone, with approximately five-times as many cases in men as in women. According to Cancer Research UK, the number of cases of mesothelioma in the UK each year is expected to rise dramatically over the next 20 years because of the heavy use of asbestos in industry from the end of the second world war up until the mid-1970s. Mesothelioma in the chest (pleural mesothelioma; PM) is much more common than in the abdomen (peritoneal mesothelioma).

Recent work by Rosetta Genomics and New York University demonstrated the potential of miR-31, an miRNA that has recently been characterised as a suppressor of breast cancer metastases, to be used for the development of new therapies against mesothelioma and other cancers. In the study, published in the 12th May online edition of the Journal of Biological Chemistry (10.1074/jbc.M110.100354), cell lines derived from mesothelioma patients were found not to express miR-31. Functional assessment of miR-31 activity revealed its ability to inhibit proliferation, migration, invasion and clonogenicity of mesothelioma cells. The reintroduction of miR-31 suppressed cell cycle and inhibited expression of multiple factors involved in co-operative maintenance of DNA replication and cell cycle progression.

miRNAs, described as the body's master switches, hold significant potential for therapeutic applications, and have been shown to be highly-sensitive and specific biomarkers in recent work. Kenneth A Berlin, President and CEO of Rosetta, commented: "This latest publication is another demonstration of miRNAs' potential role in cancer therapeutics and details the significant impact a single miRNA can have on disease course." Using its diagnostic tests for cancer, and robust and diverse miRNA-based product pipeline, Rosetta plans to continue its research in this field by harnessing the power of miRNAs.

A further development in mesothelioma also occurred in May, as MolMed received clearance from the FDA for the IND application filed to initiate a Phase III trial of its investigational antitumour drug, NGR-hTNF, for the treatment of malignant PM (MPM). The study, NGR015, is a pivotal randomised, double-blind, placebo-controlled, international, multi-centre, Phase III trial, expecting to enrol adult patients affected by MPM with disease progressing after chemotherapy. The main endpoint of the trial is overall survival; secondary endpoints include progression-free survival, disease control rate, safety and patient quality of life. Based on the positive results of a multi-centre, Phase II study, this Phase III trial is optimally designed to investigate the full therapeutic potential of NGR-hTNF in the treatment of MPM. If positive data are yielded from this study, NGR-hTNF may represent a novel treatment option for malignant mesothelioma.

Alice Rossiter
Editor, Cancer Drug News

New findings could advance fight against BC

Recent findings by scientists could help advance the fight against breast cancer (BC). A team at the University of Kentucky (UoK) Markey Cancer Center has identified a key molecular mechanism in BC that enables tumour cells to metastasise, while a separate study has uncovered five new regions of the genome that increase a woman's risk of developing the disease by between 6 and 16 per cent.

The work conducted by the UoK could lead to new lines of research aimed at developing treatments for metastatic BC (MBC). The research, published in the 13th April online issue of The EMBO Journal (10.1038/emboj.2010.63), focused on the process by which tumour cells stop clinging to other cells and become motile. The increased motility of tumour cells at the initial step of metastasis is similar to epithelial-mesenchymal transition (EMT). In all EMT processes, cells lose the expression of E-cadherin, which functions as a "molecular glue" that attaches cells to one another. The team explained that when E-cadherin is broken down, tumour cells start to migrate and spread throughout the body.

A protein called Snail acts as a master switch in the cell's nucleus to suppress E-cadherin expression and induce EMT in the cell. Agents that can disrupt the interaction of Snail are thought to have great therapeutic potential for treating MBC. Leading on from these findings, the scientists at the UoK are keen to develop drugs that can treat metastatic cancer.

Separately, a study funded by Cancer Research UK (CRUK) and the Wellcome Trust has found five new regions of the genome that increase a woman's risk of developing BC by between 6 and 16 per cent. As more of these low-risk sites are found, scientists believe that it may be possible to create tests for a combination of them that together significantly increase risk, which could ultimately help doctors to make decisions about prevention, diagnosis and treatment for women who are more likely to get BC.

The scientists scanned the entire genetic code of over 4,000 women with BC and a family history of the disease for genetic variations that appeared more often compared to healthy women. They then tested the most promising regions in over 12,000 women with BC and 12,000 women without the disease in an international collaboration. Although the results now take the total number of gene regions linked to the risk of BC to 18, scientists are still unsure which genes are causing this increased risk. Lead author, Professor Doug Easton, director of CRUK's Genetic Epidemiology Unit at the University of Cambridge, commented: "While each of these sites have a small impact on breast cancer risk, by finding more of these genes, we may be able to develop a test that can predict more reliably a woman's risk of developing breast cancer."

Alice Rossiter - Editor, Cancer Drug News

Neutropenia still prevalent despite drug availability

According to findings from a pan-European patient and nurse survey presented at the 7th Annual European Oncology Nursing Society (EONS) Spring Convention, held from 15th to 16th April, in the Hague, the Netherlands, 30 per cent of patients surveyed experienced an infection as a result of chemotherapy (CT), 45 per cent of which were associated with neutropenia or febrile neutropenia (FN). These results suggest that despite the widespread availability of prophylactic treatments, a significant number of cancer patients continue to be affected by neutropenia and its consequences.

The survey, which was sponsored by Amgen, was conducted by the EONS in nine European countries to explore current perceptions and issues relating to cancer therapy and infection, specifically neutropenia and FN. The survey found that 57 per cent of patients with an infection required hospitalisation, whilst 37 per cent had to have their CT delayed or changed as a result of neutropenia, infection or FN. More than nine out of ten nurses questioned agreed that preventing infections, such as FN, is important to achieve a successful outcome for patients undergoing CT. Kay Leonard, EONS Board Member, commented: "The survey results suggest that the risk of neutropenia and the impact this can have on patients' clinical care and quality of life must be taken even more seriously...it is important to ensure patients are receiving the most effective and appropriate prophylactic therapies as early as possible to help achieve positive treatment outcomes and prevent related complications before they develop."

Treatments are available to prevent and manage CT-induced infections, and significant progress has been made in the development of proactive therapies to help manage side effects of CT. For example, in March, the European Medicines Agency's CHMP adopted a positive opinion recommending the granting of a marketing authorisation for Hospira's Nivestim (filgrastim), a recombinant human G-CSF intended for the treatment of neutropenia. This medicine has been shown to be similar to Amgen's Neupogen (filgrastim), which is already authorised in the EU for the same indication and as one of the company's major products, achieved 2009 sales of US$1,288 million. Further, Sandoz' (Novartis) Zarzio (filgrastim) was launched in the UK last year and has been shown to have an efficacy and safety profile comparable with Neupogen, but is 10 per cent less expensive.

Many recombinant human G-CSFs are available to treat or prevent neutropenia, and therefore reduce associated complications. This is reflected in 54 per cent of nurse survey respondents who confirmed using G-CSFs prophylactically to prevent FN in patients receiving CT. An additional 27 per cent of nurses reported using both G-CSFs and antibiotics, however, 85 per cent of nurse respondents expressed concerns regarding patient compliance to treatment.

Moreover, it was reported by patients in the survey that access to and provision of treatments that prevent infection varies widely across Europe. A significant number of patient respondents did not appear to fully understand their risk of developing FN, which suggests a need for improvement in communication between patients and healthcare providers.

Alice Rossiter
Editor, Cancer Drug News

Skin cancer rates rapidly rising

In line with its launch of the 2010 SunSmart campaign, Cancer Research UK (CRUK) has revealed that people aged 60 to 79 years of age are now over five-times more likely to be diagnosed with malignant melanoma (MM) than their parents would have been 30 years ago.

Of all ages, this generation has seen the biggest increase in incidence rates of melanoma, rising from seven cases per 100,000 people in the mid-1970s to 36 cases per 100,000 today. This rise shows the impact that a shift in tanning behaviour has had on a whole generation of men and women who would have been in their 20s and 30s in the 1970s, when holidays in the sun became cheap and popular, and sunbeds arrived in the UK.

According to CRUK statistics, the most common kind of skin cancer is non-melanoma skin cancer. More than 75,000 cases are registered each year in the UK, but it is estimated that the actual number is at least 100,000. More than 10,400 cases of MM are diagnosed each year in the UK and more than 2,000 people a year die from the disease.

For men in their 60s and 70s, the rates of melanoma have risen most dramatically; they are over seven-times more likely to be diagnosed with the disease than in the 1970s. For men and women of all ages, melanoma incidence rates have quadrupled since the 1970s. This rise in incidence rates is expected to continue: by 2024, rates in people aged 60 to 79 are predicted to increase by one-third from current statistics. Caroline Cerny, SunSmart manager at CRUK, commented: "The battle against melanoma is far from won. Today, the problem threatens to get worse as teenagers continue to crave a tan on the beach and top it up cheaply on sunbeds."

CRUK also noted that there has been a large increase in the overall death rates. Over a similar period, they have more than doubled from 1.2 per 100,000 in 1971 to 2.6 per 100,000 in the UK in 2007. If melanoma death rates had stayed the same as they were in 1973, approximately 19,000 fewer people would have died from the disease.

Although the incidence rates are predicted to rise, there are currently many promising drugs in development for MM. Of particular note, Pain Therapeutics (PT) recently reported encouraging clinical data with PTI-188, an early-stage drug for MM. Although efficacy was not a primary endpoint, PT and its clinical investigators were encouraged by the number of melanoma tumours that had either stabilised or decreased in size after a single dose of PTI-188. Further, Vical recently completed enrolment of the planned 375 subjects in its multi-national, Phase III trial of Allovectin-7 in patients with MM. Allovectin-7 is a novel gene-based immunotherapeutic with a unique mechanism of action that is fundamentally different from currently-approved treatments and has the potential to be the first new primary treatment approved for MM in nearly 20 years.

Alice Rossiter
Editor, Cancer Drug News

HRT linked to LC risk

Women who take hormone replacement therapy (HRT) are at an increased risk of developing lung cancer (LC), new research by the Oregon Health and Science University suggests. As published in the 16th February online edition of the Journal of Clinical Oncology (10.1200/JCO.2009.25.9739), women aged 50 to 76 years who take oestrogen plus progestin (O+P) may have an increased risk of the disease.

According to the researchers, although the risk is duration-dependent, with women taking HRT for ten or more years at greatest risk of developing LC, an acceptable length of HRT has yet to be determined. However, it was noted that while the risk of developing LC for women using O+P for ten years or longer was approximately 50 per cent more than women not using HRT, this risk is small compared to the risk from smoking.

The scientists reviewed data collected from 2000 to 2002, and identified 36,588 peri- and postmenopausal participants aged 50 to 76 years who met their study criteria and followed them for six years. At the end of the observation period, December 2007, 344 of the participants had developed LC. After adjusting for smoking, age and other factors that affect the risk of the disease, the researchers determined that the use of O+P for ten or more years was associated with an increased risk for LC, compared with no use of HRT. They also found that the duration of use was associated with an advanced stage of cancer at diagnosis.

This research is not the first to highlight the risk of HRT use with LC. Scientists from the University of California, Los Angeles Medical Center previously reported that HRT using O+P increases the risk of death from LC. After the eight-year total follow-up from the study, published in the 20th September 2009 online edition of The Lancet (10.1016/S0140-6736(09)61526-9), the researchers found that more women died from LC in the combined HRT group than in the placebo group (73 compared to 40 deaths). In other words, women in the HRT group were 71 per cent more likely to die.

Further, it is not just an increased risk of LC that has been linked with HRT. According to results from a Stanford University study, published in the 5th February 2009 edition of the NEJM (2009;360:573-587), postmenopausal women who take combined O+P menopausal hormone therapy for at least five years double their annual risk of breast cancer. This multi-centre study also found that women on HRT can quickly reduce their risks of cancer simply by stopping the therapy.

Research such as this suggests that postmenopausal women, especially current smokers or long-term past smokers, should carefully consider these risks before initiating or continuing combined O+P use.

Alice Rossiter
Editor, Cancer Drug News

Scientists establish link between deprivation and poor prognosis for BC

Deprivation has long been known to play a role in the development of a wide range of diseases, and to a higher risk of recurrence or death for patients diagnosed with a number of cancers. Previously, the effect of material deprivation on cancer survival in England and Wales was measured by Cancer Research UK, and results showed that cancer survival for adults is generally lower among patients in more deprived groups, even after allowance is made for the higher mortality from all causes of death in these groups.

The reasons for survival rates differing between breast cancer (BC) sufferers from poorer areas and more affluent areas has never been fully understood. Now, researchers from the University of Dundee have established a link between deprivation and the p53 gene, which explains why women from poorer backgrounds are less likely to survive BC. The team identified, for the first time, that p53 mutation in BC is associated with socio-economic deprivation, and that this helps account for the poorer prognosis for women from deprived communities.

As detailed in the 26th January online edition of the British Journal of Cancer (10.1038/sj.bjc.6605540), the scientists found that women from deprived backgrounds were more likely to experience a mutation of p53, and that this linked to higher relapse and mortality rates. According to the team, there are two ways that p53 mutations can come about; one is as a result of genetic predisposition and the other is as a result of lifestyle. Smoking, drinking and poor diet can lead to p53 mutations, and are more common in women from lower socio-economic groups, who are also more likely to experience a recurrence of the disease and to die as a result of BC.

The survey looked at a total of 246 women who underwent treatment for BC between 1997 and 2001. Examining frozen tissue, tests were carried out to determine p53 mutation status. Using the patients' postcodes, a deprivation score was attributed to each and examined against the outcome (full recovery, relapse, death). The team found that patients in the lowest socio-economic group were significantly more likely to have a relapse and die compared to those in more affluent categories. They also demonstrated that the worse survival and shorter disease-free interval in BC for the most deprived patients is associated with tumour p53 mutation.

This research demonstrates a strong link between p53 and deprivation, and then between p53 mutation and recurrence and death. The social application of this work would suggest that if deprivation can be targeted, then the deprived population would be less likely to have problems with their p53 gene and go on to develop BC. In reality, this is unlikely to be achieved, however, there has been numerous work surrounding the p53 protein: Cyclacel Pharmaceuticals' seliciclib (CYC202) is a promising anticancer agent that promotes cancer cell death by downregulation of key proteins, such as p53 and Mcl-1, associated with survival of cancer cells; and new research by Dartmouth Medical School has shown that p53 limits the growth of cells with incorrect numbers of chromosomes and prevents their progression toward cancer.

Alice Rossiter
Editor, Cancer Drug News

Melanoma drugs potentially harmful to some patients

It is well known within the scientific community that the BRAF gene is faulty in approximately half of malignant melanomas and many other cancers, making it a suitable drug target. Drugs that block BRAF function in cells are already showing positive results in early clinical trials in melanoma. While the long-term effects of these drugs are not yet known, two new reports have suggested that these drugs may have unintended consequences in patients whose tumours lack mutations in the BRAF gene.

In separate studies, conducted by researchers in the US, from the Memorial Sloan-Kettering Cancer Center, and the UK, by the Institute of Cancer Research (ICR), scientists tested the drugs to better understand how they behave in cells, and found that they spurred the growth of some tumours. These preliminary findings raise the possibility that certain patients should not receive BRAF inhibitors, as they could make their cancers worse.

Based on these studies, it is thought that giving these drugs to patients whose tumours have normal copies of the BRAF gene could accelerate tumour growth. The findings suggest that physicians need to avoid treating patients who do not have certain genetic mutations, as they could potentially cause harm. The drugs primarily target a mutation in the BRAF gene, called V600E. Many, but not all of the patients enrolled in clinical trials of BRAF inhibitors have had this mutation in their tumours. The alteration is present in approximately half of all melanomas and it activates growth-promoting messages from the MAPK signalling pathway.

The new studies focused on tumours that had mutations elsewhere in the pathway. Both groups found that BRAF inhibitors can promote tumour growth in melanoma cells that lack the V600E mutation by activating other elements of the pathway. The researchers proposed several models that could potentially explain how a drug designed to inhibit the pathway could lead to its activation. The US study's first author, Dr Georgia Hatzivassiliou, of Genentech (Roche), noted that the new results, which were published in the 3rd February online edition of Nature (10.1038/nature08833), clearly indicate that the effects of BRAF inhibitors depend on the cellular context of a tumour cell. For instance, both research teams found that the drugs could activate BRAF signalling in melanoma tumours with mutations in the RAS gene, which is part of the BRAF pathway.

As reported by the ICR in the 22nd January issue of Cell (2010;140:209-221), the drugs fuelled rather than blocked the growth of melanoma cells with RAS mutations. Both studies concluded that a central player in the activation of the BRAF pathway was a protein, called CRAF, which is a close relative of BRAF. These findings provide a framework for understanding possible mechanisms of resistance to BRAF inhibitors and give researchers information about where to look in the signalling pathway.

This work has large implications, with every tumour being different; understanding more surrounding the biology of these tumours may allow scientists to develop better treatment options. Further, the impact of this research will enable physicians to target treatments more precisely to patients who will definitely benefit, and avoid treating those who will not. The financial impact of these findings is at present unknown, however, there are BRAF inhibitors currently in clinical development. Plexxikon's PLX4032 (also known as RG7204), which is in-licensed by Roche, is currently in an open-label, single-arm, Phase II trial, called BRIM2 (B-Raf Inhibitor in Melanoma), in previously-treated metastatic melanoma patients, and recently entered a pivotal Phase III trial, BRIM3, for the same indication.

Alice Rossiter
Editor, Cancer Drug News

Positive data presented at recent LC conference

At the recent AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer in Coronado, CA, many positive advances were presented, including a new study, which suggested that retreating non-small cell lung cancer (NSCLC) patients with AstraZeneca's Iressa (gefitinib) could have a beneficial effect, Phase II study results of ASA404 (vadimezan) in patients with either squamous or non-squamous NSCLC and preclinical results showing that Synta Pharmaceuticals' STA-9090 is active against 100 per cent of all NSCLC cell lines tested.

With regard to the gefitinib study, researchers evaluated 15 patients who were retreated with the drug after more than one cycle of chemotherapy for advanced or metastatic NSCLC. Among the six patients who had showed partial response (PR) with initial gefitinib treatment, two patients showed an additional PR and three continued to show stable disease (SD). Among the nine patients who showed SD with the initial gefitinib treatment, two patients showed PR and three showed SD. The overall disease control rate was 66.7 per cent.

Separately, ASA404 showed promise in patients with either squamous or non-squamous NSCLC. These results support ongoing Phase III studies of the drug in NSCLC. Under development by Novartis, which licensed the drug from Antisoma, ASA404 has a unique mechanism of action against a tumour's blood supply. The product has been shown to cause selective disruption of the established tumour vasculature, inhibition of tumour blood flow and tumour necrosis. This unique mechanism of action could provide an option for patients with either squamous or non-squamous NSCLC. Treatment options for patients with advanced-stage NSCLC are limited, particularly for those with squamous histology where some treatments exhibit limited efficacy or serious side effects.

Further, preclinical results showed that STA-9090, a potent, synthetic inhibitor of heat shock protein 90, demonstrated potent activity against 100 per cent of all NSCLC cell lines tested, including those with EGFr, HER2 or KRAS mutations, including the EGFr T790 mutation that is present in approximately 50 per cent of cases of erlotinib or gefitinib resistance. Synta is currently enrolling patients in a single-arm, open-label, single-agent, Phase II study of STA-9090 in patients with Stage IIIb or IV NSCLC, with patient cohorts defined by the genetic profile of their tumours.

STA-9090 potently inhibited cell proliferation in 24 out of 24 human NSCLC lines tested, irrespective of EGFr, HER2 or KRAS mutational status. In vivo, STA-9090 stopped tumour growth in both erlotinib-sensitive and -resistant NSCLC xenograft models. In addition, in a HER2-positive adenosquamous LC study, three out of four animals treated with STA-9090 experienced partial responses, as measured by MRI. Dr Vojo Vukovic, Chief Medical Officer of Synta, stated: "taken together, the in vitro and in vivo results presented at this conference demonstrate the potency, broad activity and safety profile of STA-9090, both as a single agent and in combination with taxanes in NSCLC."

Alice Rossiter
Editor, Cancer Drug News

Advances in skin cancer R&D

The last week has seen notable advances in the field of skin cancer research and development, including the initiation of Plexxikon's pivotal Phase III trial of PLX4032 in patients with metastatic melanoma (MM), detailed results of Biofrontera's Phase III comparative study of BF-200 ALA for the treatment of actinic keratosis (AK) and a new study from Stanford University suggesting that an anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans.

Enrolment has been initiated and the first patient has been dosed in the pivotal Phase III trial of PLX4032, a novel, oral and highly-targeted drug that is designed to inhibit the BRAF cancer-causing mutation that occurs in approximately 50 per cent of melanomas. The randomised, controlled trial, called BRIM3 (BRAF Inhibitor in Melanoma), in previously-untreated patients is part of the planned registration programme for PLX4032. With some tumour shrinkage in nearly all mutation-positive melanoma patients, and 70 per cent of patients achieving at least 30 per cent tumour shrinkage in the company's most recent clinical study, PLX4032 has shown meaningful antitumour activity. BRIM3 is expected to enrol approximately 700 previously-untreated melanoma patients who will be randomised 1:1 with PLX4032 960mg twice daily or dacarbazine.

Separately, detailed results of Biofrontera's Phase III comparative study have confirmed the superiority of BF-200 ALA over Photocure's Metvix (methylaminolevulinate) for the treatment of AK. Patients were treated by photodynamic therapy, combining one of the test compounds or a placebo with a brief red light illumination. With different types of red light sources, BF-200 ALA on average erased all lesions in 78 per cent of the patients, whereas the registered comparator, methylaminolevulinate, only reached a complete healing rate of 64 per cent, and the placebo group of 17 per cent.

Further, according to researchers at Stanford University School of Medicine, a widely-available anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans. The scientists believe that although oral administration of celecoxib is associated with an increased risk of myocardial infarction and stroke in some people, it is possible that topical application could have a safer, protective effect for people prone to developing basal cell carcinomas (BCCs). The investigators dovetailed studies in mice with a randomised, double-blind, Phase II trial to reach their conclusions.

The researchers enrolled 60 people with a genetic predisposition to BCC in a three-year trial. Approximately half of the patients received celecoxib 200mg twice daily in a tablet format, while the others received a placebo. All patients were monitored at three-month intervals at one of four study sites for the development of new BCCs or the growth of previously-identified cancers. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumours by approximately 50 per cent, as compared to placebo, in participants who entered the trial with 15 or fewer BCCs. Celecoxib treatment also reduced the overall tumour burden in this group of patients.

Alice Rossiter
Editor, Cancer Drug News

Scientists battle cancer drug resistance

A main cause of failure in the treatment of cancer is the development of drug resistance by the cancer cells. Much research is already under way to investigate ways of reducing or preventing chemotherapy (CT) resistance. Now, scientists from Kingston University, London, the UK, have begun a three-year study to analyse why cancer patients become resistant to treatments designed to fight the disease. The team has been awarded £99,000 to investigate why some tumours are sensitive and respond to treatments, and why other tumours do not. The study, funded by cancer charity, BRIGHT (Better Research into Gastrointestinal Cancer Health and Treatment), will look at existing treatments for colorectal cancer (CRC).

Experts from Kingston's Faculty of Science will work with specialists at Royal Surrey County Hospital to examine tumour specimens from CRC patients. They aim to identify signs or markers that could indicate how patients respond to treatment with anticancer drugs. The scientists will also investigate whether cancer stem cells (SCs) play an important role in the progression of CRC, and could be responsible for the poor response or development of resistance to treatment with anticancer drugs.

The study could help local health authorities to target drugs more effectively and spare those who will receive no significant benefit from treatment with what are often expensive drugs. The researchers want to investigate why it is that after several cycles of CT, resistance to the CT agents occurs. Ultimately, the team hopes that the results of the investigation will improve survival among cancer patients. It should also help scientists to develop new drugs to target those patients who do not respond well to medication currently available.

Further research in the field of resistance to cancer therapy could come from a new exclusive licence between Clarient and Minerva Biotechnologies. Minerva has granted Clarient the exclusive right to develop and commercialise a test that identifies the MUC1* protein, a biomarker researchers believe may be implicated in the spread of many cancers, including breast cancer. Early research has demonstrated that MUC1* may play a role in developing resistance to cancer drugs, which means that if scientists can block MUC1*, patients may be able to overcome resistance to a drug and, once again, be offered that therapy.

The MUC1 story has garnered a great deal of attention recently with Minerva's discovery that MUC1 is in an altered form, called MUC1*, on embryonic SCs and cancer cells. This is the first direct evidence that cancer cells grow by hijacking a normal SC mechanism that usually exists in a dormant state on healthy adult cells. Minerva has compelling evidence that cancer cells that grow resistant to anticancer drugs do so by producing more MUC1*. A recent study by Minerva outlined how the blocking of MUC1* can reverse an acquired resistance to cancer drugs, increasing the therapeutic choices for certain solid tumours.

Alice Rossiter - Editor, Cancer Drug News

Various positive data disclosed at AACR-NCI-EORTC meeting

Scientists, pharmaceutical companies and industry experts from around the world recently gathered at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held from 15th to 19th November, in Boston, MA, where much encouraging data were presented regarding a wide range of cancer indications. Of particular note, positive data were reported from studies in metastatic melanoma, lymphoma, and head and neck cancer.

Initial data from an ongoing Phase IIa study of Myriad Pharmaceuticals' Azixa (MPC-6827), a microtubule destabilising agent in Stage IV melanoma patients, demonstrated encouraging durations of response. The combination of Azixa at all concentrations with fixed-dose temozolomide, including the previously-determined single-agent maximum tolerated dose of Azixa, was safe and well tolerated. Ten patients achieved stable disease (SD) and two achieved confirmed partial responses (PRs). One patient had SD for four months before achieving a PR for an additional eight months. A second patient had SD for two months before achieving a PR for an additional four months.

Further, data from a Phase I study demonstrated that TopoTarget's belinostat (PXD101) in combination with Velcade (bortezomib) is well tolerated in patients with advanced solid tumours or lymphoma. A total of 22 were evaluable for toxicity and received a total of 58 treatment cycles. At the highest dose level, dose-limiting toxicity included Grade 4 thrombocytopenia and fatigue. Most adverse events (AEs) have been mild to moderate and four patients have maintained SD for four to six cycles of therapy.

Professor Peter Buhl Jensen, CEO of TopoTarget, commented: "we now know that full doses of belinostat can be given with full Velcade doses. This promising combination can now be tested in larger populations...belinostat may become an important treatment alone or may be part of an effective combination treatment as the safety profile of belinostat allows it to be combined in full dose with conventional and novel therapies like Velcade."

Separately, updated results from a Phase I/II trial (REO 011) of Oncolytics Biotech's Reolysin combined with carboplatin and paclitaxel (CP) for patients with advanced cancer, with a focus on H&N cancer, demonstrated that Reolysin was well tolerated when administered intravenously in combination with CP. Of 19 evaluable patients with H&N cancer, mostly squamous cell carcinoma of the H&N refractory to prior platinum-based chemotherapy for recurrent/metastatic disease, eight experienced PRs and six had SD. The total clinical benefit rate observed in H&N cancer patients in the trial was 74 per cent. Of four patients with malignant melanoma on the trial, one experienced a PR and one had SD.

Alice Rossiter - Cancer Drug News Editor

New direction needed for PC research

The current focus on individualised care in many different cancer indications has left pancreatic cancer (PC) behind. Patients diagnosed with this disease live no longer today than those diagnosed two decades ago, despite numerous amounts of clinical trials. Whilst there have been great advances in other cancers, with patients benefiting from targeted drugs such as Gleevec (imatinib) and Herceptin (trastuzumab), PC still remains aggressive as ever.

Published in the 26th October online edition of the Journal of Clinical Oncology (10.1200/JCO.2009.21.9022), an expert panel convened by the National Cancer Institute has issued a consensus report that discusses many aspects of developing and testing treatments in this disease, and charts a course for the next five years. The authors of the report have stressed that the recommendations be strongly considered in any clinical trial being planned for PC.

A recommendation is to design pilot studies that test potential treatments in smaller groups before proceeding to larger trials, which have previously yielded disappointing results. Decisions about which molecular targets and potential drugs to pursue will be made based on scientific evidence that will include preclinical and animal studies that better represent PC in humans.

As the report notes, a better understanding of the complex signalling pathways in pancreatic tumours and the role of the local tumour environment are needed. More sophisticated modelling systems and repositories of high-quality biological samples that can be shared among preclinical researchers are also essential. Published in the same issue the Journal of Clinical Oncology (10.1200/JCO.2009.24.2446), a study provides an example of the kinds of trials many in the field hope to avoid in the future. As has been the pattern for these studies, patients saw little or no benefit from the experimental treatment, in this case, a combination of gemcitabine and capecitabine, as compared with gemcitabine alone.

Scientists involved in clinical trials for PC are aware of the limited success, and have already begun to adopt new ideas about developing and testing treatments. Dr Philip A Philip, the report's senior author, commented: "we have to be more thoughtful and innovative in bringing forward new targeted therapies and treatment combinations." The hope is that the new strategy will ensure that resources and patient time are spent on the most promising treatments.

Separately, in findings that could help researchers focus their drug-development efforts, Massachusetts Institute of Technology cancer biologists have identified a subpopulation of cells that can give rise to PC. In mouse models, they also found that tumours can form in other, more mature pancreatic cell types, but only when they are injured or inflamed, suggesting that PC can arise from different types of cells depending on the circumstances. In future studies, the MIT researchers plan to use their mouse models to follow the molecular events that take place during PC development, and identify potential targets for drug treatments and protein markers for early diagnosis. These new mouse models could also help researchers test potential PC treatments.

Alice Rossiter - Cancer Drug News Editor

2,000 UK women denied BC treatment

Patients suffering from an aggressive form of breast cancer (BC) are being failed by the NHS and deprived of more treatment options as the National Institute for Health and Clinical Excellence (NICE) rejects GlaxoSmithKline's oral Tyverb (lapatinib) in combination with capecitabine for the treatment of ErbB2-positive BC.

BC is now the most common cancer in the UK. In 2006, >45,500 women were diagnosed with the disease; that is approximately 125 women a day, and in the last ten years, incidence rates in the UK have increased by 6 per cent. As an oral treatment, lapatinib gives patients suffering from ErbB2-positive BC the freedom to spend precious additional months with friends and family without the restrictive ties of regular hospital visits.

The decision to deny NHS patients access to treatment with lapatinib follows the request in July by NICE's Appeal Panel that the Appraisal Committee should reconsider lapatinib under the Institute's end of life (EOL) supplementary guidance. The EOL guidance was specifically developed to help small numbers of patients who have only a few months to live, gain access to important new medicines. GSK submitted additional data demonstrating that lapatinib met all three of the EOL criteria.

NICE recognised that lapatinib met the EOL criteria, acknowledging that additional data submitted by GSK demonstrated that the drug could offer a significant extension to life, but it felt lapatinib was still not a cost-effective use of NHS resources. This decision has been made despite GSK offering the Tyverb patient access programme, which allows NHS patients in the UK free access to lapatinib for the first three months of treatment.

GSK proposed the patient access programme in the UK when NICE indicated early on in its review that it did not consider lapatinib to be cost effective in treating this patient population. The company will continue to honour the access programme for NHS trusts in the UK. A total of 26 trusts have already enrolled in this programme, reflecting the clinical demand for lapatinib and recognising the potential cost effectiveness for the NHS. Simon Jose, General Manager of GSK UK commented: "it is disappointing that, despite acknowledging Tyverb meets these criteria and GSK offering to bear the cost of lapatinib for up to 12 weeks, NICE is still proposing to reject lapatinib. We will continue to offer our patient access programme to individual NHS Trusts to ensure patients have access to Tyverb."

This decision will result in 2,000 UK women a year being denied access to lapatinib on the NHS. These are women for whom there are very few other treatment options available to them at this stage of their disease. By comparison, lapatinib is funded in 18 other European countries for the treatment of women whose advanced BC has returned despite treatment with standard chemotherapy regimes, including intravenous Herceptin (trastuzumab).

Alice Rossiter - Cancer Drug News Editor

Cancer proven to pass from mother to baby

A rare case of a mother and her infant developing the exact same cancer has allowed an international team of researchers from the Institute of Cancer Research (ICR), to solve a puzzle that has perplexed scientists and clinicians for a century. The scientists, with funding from Leukaemia Research, investigated a situation in which leukaemic cells appeared to have defied accepted theories of biology and spread through the womb from a Japanese woman to her daughter.

Approximately 30 previously-known cases of a mother and infant appearing to share the same cancer had already raised suspicions that such spread was possible. However, there was no genetic evidence to support this theory, and investigators did not know how it could occur as the baby's immune system should have recognised and destroyed any invasive cancer cells that were of maternal, and therefore foreign, origin. In a study, published in the 12th October online edition of PNAS (10.1073/pnas.0904658106), the scientists used advanced genetic fingerprinting to prove for the first time that the infant's leukaemic cells were unquestionably of maternal origin.

The researchers found that both patients' leukaemic cells carried the identical mutated cancer gene, Bcr-Abl1, but the infant had not inherited this gene. This meant that the child could not have developed this type of leukaemia in isolation. To investigate how the cells could have crossed the placental barrier and survived in the offspring, the scientists looked for evidence of some form of immunological acceptance or tolerance of the foreign cells by the foetus. They examined the genes of the cancer cells in the infant and found some DNA missing in the region that controls expression of the major histocompatibility locus. This was significant because HLA molecules primarily distinguish one individual, and his or her cells, from another, so the absence of these molecules on the cancer cells meant that the infant's immune system would not have recognised that they were foreign.

It appears that in this and, the scientists presume, other cases, the maternal cancer cells did cross the placenta into the developing foetus and succeeded in implanting because they were invisible to the immune system. Dr David Grant, Scientific Director at Leukaemia Research, commented: "the important message from this fascinating piece of research is that leukaemia cells can be destroyed by the immune system. Harnessing the power of the immune system to first cure and then protect patients from leukaemia is one of our priority areas of research."

According to Professor Peter Johnson, Cancer Research UK's Chief Clinician, this finding provides further evidence that cancers are generated more often than first thought. A large part of cancer research is on cancer immunity; scientists have known for quite some time that people with deficient immune systems, perhaps because of HIV or immunosuppression after organ transplants, are much more prone to certain types of cancer. The real challenge for researchers now is to work out how to invigorate the immune system so it recognises cancer cells.

Alice Rossiter
Cancer Drug News Editor

Vaccination and testing for HPV could eradicate CC

According to a cervical cancer (CC) screening expert, Professor Jack Cuzick, from Cancer Research UK, the disease could be eradicated within the next 50 years if countries implement national screening programmes based on the detection of the human papillomavirus (HPV). Cuzick told the recent joint 15th ECCO and 34th ESMO Congress that while the current HPV vaccines protect against two cancer-causing strains of the HPV virus, soon there would be vaccines available that protect against nine types. If vaccination were to be combined with HPV screening, which is much more sensitive than the currently used Pap smear test, then eventually the cancer would disappear in those countries that had successfully implemented national programmes. However, this would require political will and effort at both national and European levels.

The current vaccine holds the promise of eradicating approximately 70 to 75 per cent of CC (caused by HPV types 16 and 18), and there appears to be some additional cross protection amongst types that are closely related to 16 or 18, in particular 31, 45 and a part of 33. There are new vaccines being planned that will vaccinate against nine types; if they are successful, there should be no need to screen women that have been vaccinated at all.

The Pap test relies on subjective assessments by people examining the cells in the smear with a microscope and therefore is open to human error. Cuzick believes that such errors will increase as the proportions of smears with affected cells decline due to increasing numbers of women having been vaccinated. In contrast, the HPV test is almost completely automated, is designed to detect the virus in the smear rather than relying on visual examination and therefore is much less likely to be affected by human error. Cuzick commented: "there's overwhelming evidence that HPV screening is more effective than the Pap smear test, which misses about a third to a half of all high-grade lesions". However, Cuzick warned that the EU and national governments should take the initiative in discussions on implementing screening and vaccination programmes, rather than leaving it to pharmaceutical companies to lead the debate.

During the last fortnight, much data have been reported in relation to CC drug and vaccine trials. Of particular note, results from the PATRICIA (PApilloma TRIal Cervical cancer In young Adults or HPV 008) study showed that GlaxoSmithKline's Cervarix is highly effective at protecting against the two most common CC-causing HPV types, 16 and 18. Furthermore, Cervarix demonstrated efficacy against cervical intraepithelial neoplasia 2+ lesions associated with 12 additional HPV types beyond 16 and 18, including HPV 31, 33 and 45.

In addition, Phase I trial results of ADXS11-001 have shown 36-month survival in three of the 13 evaluable patients treated with Advaxis' therapeutic cancer vaccine, which treats women who have already developed CC as a result of HPV infection, indicating the possibility of persistent immune protection. Further, interim safety and immunogenicity data from a Phase I trial of Inovio Biomedical's VGX-3100 showed that the therapeutic CC vaccine was generally safe and well tolerated, plus it achieved significant cellular and humoral immune responses at the lowest dose administered. VGX-3100 is a DNA vaccine targeting the E6 and E7 proteins of HPV types 16 and 18.

Alice Rossiter - Cancer Drug News Editor

HBV vaccine reduces HCC cases in young

A 20-year follow-up study has revealed a dramatic drop in liver cancer cases among six- to 19-year-olds who were vaccinated for hepatitis B (HBV) at birth. In July 1984, a universal vaccination programme was initiated among newborn children in Taiwan to prevent HBV infection, which can predispose to the development of hepatocellular carcinoma (HCC).

HCC is responsible for approximately 90 per cent of the primary malignant liver tumours in adults. It is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally. More than 600,000 cases are diagnosed worldwide each year (>400,000 in China, South Korea, Japan and Taiwan, 54,000 in the EU and 15,000 in the US) and the incidence is increasing. In 2002, approximately 600,000 people died of HCC, including approximately 370,000 in China, South Korea and Japan, 57,000 in the EU and 13,000 in the US.

For the study, which was published in the 16th September online edition of the Journal of the National Cancer Institute (10.1093/jnci/djp288), scientists from the National Taiwan University Department of Pediatrics collected data on 1,958 patients with HCC who were aged six to 29 years at diagnosis in Taiwan between 1983 and 2004 from two national HCC registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analysed by using Poisson regression models. All statistical tests were two-sided. Records of 64 HCC patients and 5,524,435 HBV vaccinees who were born after the initiation of the vaccination programme were compared for HBV immunisation characteristics during infancy and prenatal maternal HBV surface antigen (HBsAg) and e antigen (HBeAg) serostatus.

Results showed that HCC incidence was statistically significantly lower among children aged six to 19 years in the vaccinated cohort compared with the unvaccinated birth cohorts (64 HCCs among vaccinees in 37,709,304 person-years vs 444 cancers in unvaccinated subjects in 78,496,406 person-years, showing an age- and sex-adjusted relative risk of 0.31, p<0.001, for persons vaccinated at birth).

The risk of developing HCC for vaccinated cohorts was statistically significantly associated with: incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR]=4.32, 95% CI, 2.34 to 7.91); prenatal maternal HBsAg seropositivity (OR=29.50, 95% CI, 13.98 to 62.60); and prenatal maternal HBeAg seropositivity (with administration of HBV immunoglobulin at birth, OR=5.13, 95% CI, 2.24 to 11.71; and without it, OR=9.43, 95% CI, 3.54 to 25.11).

These data suggest that the effectiveness of the universal HBV immunisation programme to prevent HCC has extended beyond childhood and into young adulthood over the past two decades. With regard to the National Institute for Health and Clinical Excellence (NICE) recently refusing Bayer HealthCare/Onyx Pharmaceuticals' Nexavar (sorafenib) for the treatment of patients in England and Wales with HCC, despite being the only systemic treatment option that could potentially extend the survival of patients with the disease, it seems that currently, prevention is better than the cure.

Alice Rossiter
Cancer Drug News Editor

MDS patients failed by NHS

Adding weight to a previous editorial published in Cancer Drug News (see Issue No. 377 - "Is NICE depriving UK patients' options?"), the results of a new survey, launched by the UK MDS Patient Support Group, have shown that almost one-fifth (18 per cent) of patients suffering from myelodysplastic syndromes (MDS) could have lived for longer if they had been able to access treatments that are currently not approved by the UK's National Institute for Health and Clinical Excellence (NICE) for treatment on the NHS. According to current estimates, just fewer than 2,000 new cases of MDS are diagnosed in the UK each year.

The survey of 100 haematologists from England, Wales and Scotland revealed that 56 per cent of blood cancer (BC) experts believe that less priority is given to rarer cancers versus other common cancers. The majority of BC experts (89 per cent) surveyed have faced situations where they have been unable to provide treatments for their BC patients that could have potentially extended their patients' survival as these treatments were not readily available on the NHS or not yet approved by NICE.

David Hall, Chairman of MDS UK Patient Support Group, commented: "these results are alarming and distressing. Denying any patient access to life-extending, blood cancer drugs is immoral and contradicts the very principles upon which the NHS was founded. These new treatments have been thoroughly tested and their efficacy demonstrated. It is ironic that the perceived constraints to availability in the UK seem to be based exclusively on inadequate finance."

The MDS UK Patient Support Group has called upon the Department of Health to re-address this inequality by making proven treatments available to all patients whose life span may otherwise be unnecessarily curtailed. These results have highlighted the gaps in access to treatments that can prolong and improve the lives of patients living with MDS and other BCs. Despite significant advances in the treatment of MDS, the majority of patients cannot get access to and, in some cases, are not even informed about new life-extending drugs until they have been appraised and approved by NICE. The impact of waiting even a month for treatment for MDS can result in a life or death situation.

Hilary Jackson, Cancer Research UK's policy manager, noted that: "where NICE has not provided advice on a particular drug, it is up to Primary Care Trusts (PCTs) to decide which they will fund...without NICE approval, we need a fair approach to ensure that doctors, patients and the PCTs themselves are clear about how funding decisions will be made."

It seems concerning that patients are not getting access to drugs that could extend their lives, which have been thoroughly investigated and their efficacy shown, and, in some cases, are available in comparable countries.

Alice Rossiter
Cancer Drug News Editor

Is NICE depriving UK patients' options?

During the past week, the UK's National Institute for Health and Clinical Excellence (NICE) has issued mixed recommendations on the use of drugs for the treatment of renal cell carcinoma (RCC) and metastatic colorectal cancer (MCRC).

NICE has not recommended Genentech's (Roche) Avastin (bevacizumab), Bayer HealthCare/Onyx Pharmaceuticals' Nexavar (sorafenib) and Wyeth Pharmaceuticals' Torisel (temsirolimus) as first-line treatment options for advanced and/or metastatic RCC. In addition, Nexavar and Pfizer's Sutent (sunitinib) are not recommended for second-line treatment, although both are licensed in the EU for this therapy. According to NICE, the evidence to support the use of the first- and second-line treatments is not strong enough to justify using NHS funds, which could be used for other cancer treatment programmes or in other treatment areas.

In response to this NICE decision, Roche is considering all options. The Appraisal Committee accepted that Avastin in combination with interferon has a similar clinical and cost-effectiveness profile to the already-approved Sutent, but turned it down because it has a licence in other indications, despite the fact that these indications are not currently routinely reimbursed on the NHS.

John Melville, General Manager of Roche UK, commented: "this decision is entirely illogical and neither addresses the needs of patients with renal cancer, nor advances the innovation agenda. Avastin demonstrates the same value to the NHS as sunitinib and this guidance goes against the spirit of end-of-life criteria, which were devised for this very setting."

On a positive note, NICE has recommended the use of Merck Serono's (Merck KGaA) Erbitux (cetuximab) in combination with FOLFOX for the first-line treatment of MCRC, but only when all of the following criteria are met: (a) the primary colorectal tumour has been resected or is potentially operable; (b) the metastatic disease is confined to the liver and is unresectable; (c) the patient is fit enough to undergo surgery to resect the primary colorectal tumour and to undergo liver surgery if the metastases become resectable after treatment with Erbitux; and (d) the manufacturer rebates 16 per cent of the amount of Erbitux used on a per patient basis.

Further, NICE recommended that patients who meet the above criteria should receive treatment with Erbitux for no more than 16 weeks. After this period, treatment with Erbitux should stop and the patient should be assessed for resection of liver metastases. It was also recommended that people with MCRC with metastatic disease confined to the liver who receive Erbitux should have their treatment managed only by multidisciplinary teams that involve highly-specialised liver surgical services. The Appraisal Committee concluded that under the specific circumstances outlined in the guidance, the cost of Erbitux in relation to how well it works is an effective use of NHS resources.

Although the NICE guidance on the use of Erbitux means many MCRC patients will have a new treatment opinion, the decision not to recommend Avastin, Nexavar or Torisel as a first-line therapy for RCC will reduce treatment options for UK patients who are fighting this disease, yet is available for the same indication in comparable countries.

Alice Rossiter - Cancer Drug News Editor