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Pemetrexed Demonstrates Significantly Fewer Side Effects And Similar Efficacy As Docetaxel In Treatment Of Non-Small Cell Lung Cancer

Pemetrexed, used as a second-line treatment, had equivalent clinical efficacy with a significantly better safety profile compared to docetaxel in the treatment of patients with non-small cell lung cancer who had been previously treated with chemotherapy, according to the findings of a multinational randomised phase 3 trial.

"The primary objective of the study was to compare overall survival between the two treatment groups on an intent-to-treat basis," write Nasser Hanna, MD, Indiana University, Indianapolis, United States, and colleagues.

Pemetrexed is a new, multitargeted antifolate chemotherapy agent that is active in multiple tumour types including non-small cell lung cancer (NSCLC). Folate and vitamin B₁₂ nutritional status modify the toxicity of pemetrexed. Folic acid supplementation orally every day and vitamin B₁₂ intramuscular every 9 weeks is necessary to control pemetrexed toxicity.

Five hundred seventy-one eligible patients were randomly assigned to either pemetrexed 500 mg/m² intravenously (IV) over 10 minutes or to docetaxel 75 mg/m² IV over 1 hour, on day 1 of a 21-day cycle. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator demanded treatment discontinuation.

At the time of analysis 71.6% of the 571 patients had died. The median follow up for all patients was 7.5 months. All patients were assessable for survival.

The Lung Cancer Symptom Scale was administered at baseline and once a week during the study. Toxicity evaluations were assessed according to the National Cancer Institute guidelines.

There was no significant difference in response rate (9.1% vs. 8.8%) between the two groups. There were no significant differences in progression free survival, time to progressive disease and time to treatment failure. There were no significant differences in median time to response, median duration of response, and median duration of clinical benefit.

On an intent-to treat basis, the median survival time for pemetrexed was 8.3 months versus 7.9 for docetaxel. The 1-year overall survival rate for each group was 29.7%.

Patients in both groups had similar rates of improvement or stabilisation of anorexia, fatigue, cough, dyspnoea, haemoptysis and pain. All treated patients were assessable for toxicity. Treatment-related deaths were attributed to docetaxel and pemetrexed in 5 and 3 patients respectively. Patients receiving docetaxel experienced significantly higher rates of neutropaenia, neutropaenic fever, infections and hospitalisation due to neutropaenic events compared to patients receiving pemetrexed.

The use of granulocyte colony-stimulating factors was substantially increased for patients receiving docetaxel when compared to pemetrexed. There was a significantly higher rate of alopecia for patients receiving docetaxel and a slightly greater incidence of rise in ALT (alanine amino transferase) for patients receiving pemetrexed.

"Based on these results, treatment with pemetrexed should be considered a standard treatment option for second-line NSCLC," conclude the authors.

J Clin Oncol 2004 May 1;22:9:1589-97. "Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy"

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