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.”