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
Wednesday, December 2, 2009
Wednesday, November 25, 2009
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
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
Wednesday, November 11, 2009
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
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
Wednesday, October 28, 2009
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
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
Thursday, October 22, 2009
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
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
Thursday, October 15, 2009
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
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
Tuesday, September 29, 2009
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
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
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