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

Article Abstract:

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.)

Chemotherapy

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Evaluation of carboprost tromethamine in the treatment of cyclophosphamide-induced hemorrhagic cystitis

Article Abstract:

Cyclophosphamide in a cell-killing agent used to treat certain cancers and nonmalignant diseases, and to prepare patients for bone marrow transplantation. A common complication of cyclophosphamide chemotherapy is hemorrhagic cystitis, or inflammation of the bladder associated with bleeding and hematuria (blood in the urine). Bladder damage may be caused by acrolein, a metabolite of cyclophosphamide. Acrolein causes edema, ulcer formation, new blood vessel development, bleeding, and tissue death. The treatment of hemorrhagic cystitis caused by cyclophosphamide has been difficult, intensive, and costly. The effect of carboprost tromethamine, a prostaglandin agent, in treating hemorrhagic cystitis was assessed in four patients with this complication. Carboprost tromethamine was instilled into the bladder, and left there for 45 to 60 minutes three to four times a day, for four to five days. A second course of treatment with a higher dose of carboprost tromethamine was required by two patients. Treatment was discontinued after a five-day regimen in one patient because of persistent bladder spasms and hematuria. However, hemorrhagic cystitis was completely resolved in the three patients who completed the full course of treatment. Carboprost tromethamine caused only bladder spasms, which were treated with oxybutynin chloride in three of four patients. These findings demonstrate that carboprost tromethamine is safe and effective for treating hemorrhagic cystitis caused by cyclophosphamide. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Evaluation, Complications and side effects, Drug therapy, Bladder, Cystitis, Cyclophosphamide, Carboprost

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Non-small cell lung cancer

Article Abstract:

Lung cancer, both small and non-small cell, accounts for 28% and is the leading cause of cancer deaths in the US annually, and 85% of these deaths are linked to smoking. The non-small cell lung cancers (NSCLCs) are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. There are various local, metastatic, and paraneoplastic symptoms, so NSCLCs must be diagnoised by physical examination, imaging techniques, patient history, and pathologic specimens. Treatment for NSCLCs include surgery, radiation, chemotherapy, and brachytherapy.

Analysis

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