Category Archives: Mesothelioma – Latest Research.
Latest Clinical Trial Involving Pemetrexed and Radiation Shows Promising results In Lung Cancer Patients
The first scientific trial of an important new combination therapy of treatment with the chemotherapy drug pemetrexed in conjunctionwith radiation in lung cancer patients has delivered promising results, according to a French researchers report at the second ‘European Lung Cancer Conference’.
The results of the Phase I trial suggest that pemetrexed, (unlike some other newly developed chemotherapy drugs) is safely tolerated to allow it to be administered at a high dose with concurrent radiotherapy, increasing the potentialityof the treatment.
Pemetrexed is predominantly used for the treatment of pleural mesothelioma and already has a respected role in treating metastatic non-small-cell lung cancer. It has a chemical structure similar to folic acid, and prohibits the development of DNA and RNA by preventing the formation of the nucleotide bases.
Prof Françoise Mornex, head of the ‘Department of Radiotherapy Oncology at Centre Hospitalier Lyon Sud’ and colleagues carried out the first trial of the drug in combination with radiotherapy and cisplatin chemotherapy in cancer patients with stage three lung cancer (locally advanced, and not where the cancer had spread ‘metastatic’).
The trial consisted of 9 patients with no surgical intervention but stage 3 non-small-cell lung cancer. Firstly – they were administered two cyclesof chemotherapy, 3 weeks apart, with 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin. This was proceeded by two cycles of combined chemotherapy and radiotherapy, where doses of pemetrexed began at 400 mg/m2 and were then escalated to 500mg/m2 and 600 mg/m2. Cisplatin and radiotherapy at 66 Gy/33 Gy fractions over 7 weeks stayed constant.’
Out of ten patients that commenced treatment, one was omitted from the trial before dose accumulation as a result of disease progression. Out of the remaining 9 however, seven participants completed all 4 phases of chemotherapy, and 8 completed radiotherapy treatment.
Only one patient experienced toxicity on the highest dose of pemetrexed, which was recorded as a grade 4 septic shock.
These particular doses of Pemetrexed were considered to be well-tolerated when given along side with cisplatin and radiotherapy.It seems to be the only 3rd generation agent that can be favourably recommended safely at the maximumtrials with concurrent radiotherapy.
According to Professor Mornex who led the trial, these findings are important as most of the time, when combining radiation and chemotherapy concurrently, the dose of chemotherapy must be minimised somewhat due to excessive toxicity. The potential problem this presents though – is that by decreasing the chemotherapy dose, one reduces the capability of the chemotherapy on micro metastases and on the primary tumor. However – concerning pemetrexed, the tolerance is acceptable and allows for high cytotoxic doses during radiation, thus improving the chance of destroying cancerous cells.
Professor Mornex added – “This trial will have a positive impact on clinical practice in the near future,and this regimen is already being studied in several ongoing clinical trials around the world; it may become the treatment of choice in the future, for concurrent chemo-radiation schemes.”
A clinical study published – 9th February 2009, shows promising results in a new future treatment for tumours in patients with mesothelin forms of cancers. The study which was developed by researchers at the (NCI) ‘National Cancer Institute of Health’ and the ‘University of Pennsylvania School of Medicine’ may offer a fresh approach in the development of immunotherapy and certain tumours.
Elevated levels of ‘mesothelin’ – a type of protein which is usually limited to cells that make up the protective membrane (mesothelium) which encases the body’s cavities and internal organs has been found in blood samples of workers exposed to asbestos prior to any tumours being detected. Mesothelin is considered to play an important role in the metastatic rate (spread and growth) of cancers but its biological function remains unclear.
According to ‘Ira Pastan’ M.D, at (NCI) – Tumour cells derive from a persons normal cells – hence the immune system doesn’t always predict tumour molecules as being threatening or foreign and therefore fails to put up a fight or attack them. It is possible to genetically modify the immune cells to recognise and target molecules on tumour cells but molecule cells can be also present in normal cells and destroyed. However – mesothelin is a far more promising suitor for producing tumour- targeting T-cells as it is more limited to normal tissues than in several cancers.
So the research team genetically engineered some human T-cells to predominantly target human mesothelin. In order to study the effects on tumour tissue, human mesothelioma cells were implanted beneath the skin of mice. Approximately six weeks later when tumours had formed and advanced – the modified T-cells were injected into the tumours or intravenously. The results were promising as the tumours not only shrinked considerably but some disappeared.
The findings indicate that small doses of engineered T-cells may help mesothelioma and ovarian cancer patients in the future and clinical trials are currently being developed to investigate its potential.