The phase I trial of the chemotherapy drug pemetrexed (Alimta, Eli Lilly) when used simultaneously with radiotherapy for certain cases of lung cancer has proven to be well-enough tolerated to allow for high dose administration during the treatment, increasing radiotherapy’s effectiveness, researchers reported during a presentation at the second annual European Lung Cancer Conference on April 30.
Françoise Mornex, PhD, from the department of radiotherapy oncology at Centre Hospitalier Lyon Sud in Pierre-Bénite, France, and colleagues said that this combination therapy has “delivered promising results,” as Pemetrexed--a drug with a similar chemical structure to folic acid that seeks to prevent the formation of DNA and RNA by inhibiting the formation of the nucleotide bases--is unlike some other modern chemotherapy drugs, in that it can be tolerated when used with radiation.
According to the researchers, the drug is currently indicated for the treatment of pleural mesothelioma and has a role in treating metastatic non-small-cell lung cancer.
Mornex and colleagues recruited 10 patients with unresected stage III non-small-cell lung (locally advanced, but not metastatic) cancer for their study and administered two cycles of chemotherapy, three weeks apart, with 500 mg of Pemetrexed and 75 mg of another chemotherapy drug, cisplatin (Platinol-AQ, Bedford Labs).
The treatment was followed by two cycles of combined chemotherapy and radiotherapy, where the doses of pemetrexed began at 400 mg and were escalated to 500mg and then to 600 mg. Cisplatin and radiotherapy doses remained constant over the seven-week treatment period, explained the researchers.
Of the 10 patients who began treatment, one had to be excluded from the trial before dose escalation due to disease progression. Of the remaining nine, seven completed all four cycles of chemotherapy and eight completed the radiotherapy. The researchers said that one dose-limiting toxicity (grade 4 septic shock) was recorded in one patient who was on the highest dose of pemetrexed.
"Pemetrexed at these doses was well tolerated when given concurrently with cisplatin and radiotherapy," stated Mornex. "It appears to be the only third generation agent that can likely be recommended safely at full dose in trials with concurrent radiotherapy."
The researchers noted that the study’s findings are beneficial because frequently the dose of chemotherapy must be decreased due to excessive toxicity when combining radiation and chemotherapy concurrently, which can reduce effectiveness of chemotherapy on micro metastases and on the primary tumor.
"We are very happy to present these data, which will have an impact on clinical practice in the near future," concluded Mornex. "This regimen is already being studied in several ongoing clinical trials around the world [and] it may become the treatment of choice in the future.”