Fluorouracil prodrug plus gemcitabine promising for elderly with advanced NSCLC

NEW YORK (Reuters Health) - When gemcitabine is given along with an agent that's based on a fluorouracil prodrug, the combination produces considerably better overall response rates in elderly patients with non-small cell lung cancer (NSCLC), Japanese authors report.

The agent, TS-1, contains the fluorouracil prodrug tegafur and was associated with only mild toxicities in the phase I/II trial, the researchers said.

Whereas elderly patients with advanced NSCLC reportedly have response rates of roughly 10% to vinorelbine and roughly 17% to single-agent gemcitabine, the overall response rate in this trial was 27%, according to lead author Dr. Takashi Seto of the National Kyushu Cancer Center, Fukuoka, and colleagues.

As reported online February 12th in the journal Lung Cancer, 22 patients participated in the phase I portion, and 10 of these plus another 27 participated in phase II. The median age was 77 years, and 65% of patients had stage IV disease.

In phase I, the researchers tested escalating doses both agents, establishing the recommended dose at 60 mg/m2/day of TS-1 on days 1 through 14 of a 28-day cycle, and 1,000 mg/m2 IV of gemcitabine on days 8 and 15.

In phase II, no one had a complete response, but 10 patients (27%) had partial responses. Fourteen patients had stable disease, nine had disease progression, and four could not be evaluated for tumor response.

The median progression-free survival was 4.2 months, the median overall survival was 12.9 months, and the one-year survival rate was 51%.

The most common grade 3 or 4 adverse event was neutropenia (45.9%); 13.5% developed thrombocytopenia.

"The greatest concern for the use of a double regimen in the elderly is the trade-off between toxicity and survival benefit," the researchers said. But in this study, they point out, not only was the response rate "considerably higher than...previously reported response rates" but "grade 3 or higher events remained at a frequency of 2.7%, which was...considered manageable."

Next, the authors say, this combination regimen should be studied in phase III trials, and in ethnic groups other than the Japanese.

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