Temozolomide Improves Outcome of RT in Lung Cancer With Brain Metastases

Laurie Barclay, MD

August 26, 2003

Aug. 26, 2003 — The combination of temozolomide (TMZ) with whole-brain radiotherapy (WBRT) was better than WBRT alone for the treatment of lung cancer with brain metastases, according to a presentation at the 10th World Conference on Lung Cancer in Vancouver, British Columbia, Canada.

"Radiation treatment (RT) in patients with brain metastases has limited activity. We thought that combining RT with TMZ, this new alkylating agent that crosses the blood-brain barrier, might enhance the efficacy," lead author Dosia Antonadou, MD, a radiation oncologist at Metaxas Cancer Hospital in Pireus and Athens, Greece, told Medscape. "We conducted a phase II randomized study and the results were promising. Based on our previous experience we conducted this phase III study to confirm our previous findings."

Of 108 evaluable patients with histologically or cytologically proven lung cancer enrolled in this multicenter trial, 103 patients were evaluated for response by radiological assessment. Subjects were randomized to receive WBRT, 3 Gy for five days per week (total dose 30 Gy), alone or with treatment with TMZ 75 mg/m 2 per day during WBRT, followed by 200 mg/m 2 TMZ per day for five consecutive days every 28 days for six cycles, beginning one month post-WBRT.

The primary endpoint was radiological response determined by computed tomography or magnetic resonance imaging at three months after WBRT. Median follow-up was 5.56 months (range, 0.426 - 20.79).

Complete and partial response occurred in 48.0% of the TMZ plus WBRT group and in 27.5% of the WBRT alone group ( P = .031). Time to progression was significantly longer in the combined arm (7.54 months vs. 5.99 months; P = .011).

Patients in the TMZ plus WBRT group also fared better in terms of median survival (7.9 months vs. 4.3 months; P = .06), median survival in patients with multiple lesions (7.3 months vs. 4 months; P = .1248), median survival in patients first diagnosed with brain metastases and then with lung cancer (7.4 months vs. 4 months; P = .013), and median survival in patients with recursive partitioning analysis (RPA) Class II (3.8 months vs. 3.31 months; P = .05).

"Patients under the age of 60 years and in good neurologic status did significantly better in the combined treatment group," Dr. Antonadou said. "In the subgroup analysis, chemotherapy-naive patients did better, as well as patients in RPA Class II."

Median survival in patients in RPA Class I was eight months in both groups ( P = .78). No grade 3 toxicities were noted.

"There was no significant difference in survival concerning the number of brain [metastases]," Dr. Antonadou concluded. "We think that survival data have to be confirmed in a larger randomized trial having survival as an endpoint."

This study was not sponsored, and none of the authors has a financial agreement with the pharmaceutical company that makes temozolomide.

10th WCLC: Abstract O-67. Presented Aug. 11, 2003.

Reviewed by Gary D. Vogin, MD

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