Edatrexate improves the antitumor effects of cyclophosphamide and cisplatin against non-small cell lung cancer

Although several combinations of chemotherapeutic agents have shown some effectiveness in the treatment of non-small cell lung cancer, none is clearly superior and none is satisfactory. One agent that shows promise in the attempts to develop new chemotherapeutic protocols for lung cancer is edatrexate. This drug is similar in chemical structure to methotrexate and operates by a similar mechanism. Edatrexate inhibits the enzyme dihydrofolate reductase, which plays an important role in the synthesis of some of the bases necessary for DNA. A study was conducted to evaluate the effectiveness of a chemotherapeutic regimen which includes the standard chemotherapeutic agents cisplatin and cyclophosphamide, and the experimental agent edatrexate. Thirty-two patients with advanced stage non-small cell lung cancer participated in the clinical trial; none had received any prior chemotherapy. The study began with the treatment of 16 patients with a total dose of 800 mg per meter squared (milligrams per square meter of body area) cyclophosphamide, 80 mg per meter squared cisplatin, and 80 mg per meter squared edatrexate. This protocol yielded two complete responses and five partial responses. An additional five patients had minor responses. However, this regimen was poorly tolerated, and many patients developed a serious suppression of bone marrow and inflammation of the stomach. The dosage was therefore reduced by one-eighth for the next 16 patients. This reduction in dose resulted in a reduction in effectiveness as well; no patients in the second group achieved a complete response; four developed partial responses. Patients who developed a complete or partial response had a median survival time of 55 weeks. The median survival of the patients with a minor response was 39 weeks. The remaining patients survived a median of 27 weeks. This study suggests that edatrexate improves the response to chemotherapy with cisplatin and cyclophosphamide. However, the response curve is steep, meaning that a slight change in dose results in a significant change in effectiveness. It may be possible to improve the success of the treatment regimen if ways can be found to raise the dose while minimizing the adverse side effects of stomatitis and myelosuppression. (Consumer Summary produced by Reliance Medical Information, Inc.)