ASCO: Pemetrexed Doublet Better for Quality of Life in Advanced NSCLC

CHICAGO, June 5 -- Pemetrexed (Alimta) plus platinum chemotherapy for advanced non-small cell lung cancer (NSCLC) may reduce toxicity compared with a gemcitabine (Gemzar) and platinum doublet but hold little other advantage.

In a Norwegian trial, leukopenia, granulocytopenia, thrombocytopenia, and transfusions were significantly less common with the pemetrexed combination, found Bjrn Henning Grnberg, M.D., of St. Olavs University Hospital in Trondheim, Norway, and colleagues.

However, health-related quality of life and overall survival were similar for the two first-line treatment regimens, Dr. Grnberg reported at the American Society of Clinical Oncology meeting here.

Phase II trials had suggested pemetrexed plus a platinum was as effective as standard doublets but with less toxicity as first-line NSCLC treatment, he said.

So they hypothesized that "less toxic treatment might provide better quality of life for patients who often have poor performance status and significant comorbidity."

Their multicenter, phase III trial therefore looked at the two regimens primarily from a quality-of-life standpoint among 437 patients with stage IIIb or IV NSCLC (28% to 29% and 71% to 72%, respectively).

Patients were randomized to receive four cycles every three weeks of 500 mg/m² pemetrexed and carboplatin (Paraplatin) on day one, or 1000 mg/m² gemcitabine on days one and eight plus carboplatin on day one.

All patients received supplemental vitamins. Those who were age 75 or older (18%) received 75% of the full doses.

The majority of patients in both groups tolerated all four doses (72% in the pemetrexed group and 62% in the gemcitabine group).

Quality of life, the primary endpoint, was measured with questionnaires at baseline, before every cycle, three weeks after the last cycle, and then every two months until one year after randomization.

Global quality-of-life scores were similar between groups at every point.

Subscales measuring nausea and vomiting, dyspnea, and fatigue also showed no statistically significant differences between treatment regimens.

Overall survival likewise was similar at a median of 220 days after randomization with the pemetrexed doublet and 210 with the gemcitabine doublet (P=0.60), the researchers found.

There were some significant differences in toxicity, though. Comparing pemetrexed- and gemcitabine-based therapy, their findings included:

• Lower rates of grade three and four leukopenia with pemetrexed (17% versus 35% and 5% versus 9%, P