NEW YORK (Reuters Health) - Concomitant chemoradiation is better than sequential therapy for improving survival with locally advanced non-small-cell lung cancer (NSCLC), according to a patient-level meta-analysis reported online March 29th in the Journal of Clinical Oncology.

The improvement comes at the cost of increased, but manageable, acute esophageal toxicity, the researchers say.

Lead author Dr. Anne Auperin from Institut Gustave-Roussy, Villejuif, France, and colleagues note that in most individual trials, adding sequential or concomitant chemotherapy to radiation led to improved survival in patients with locally advanced NSCLC.

To directly compare the sequential and concomitant approaches, the investigators conducted a systematic search for published and unpublished trials. They identified 7 randomized trials and requested the data on all patients: gender, age, date of randomization, treatment assignment, performance status at randomization, tumor stage, histopathology, and updated information on survival, recurrence, cause of death, and acute toxicity.

Ultimately, their meta-analysis included data from 6 trials involving 1205 patients (92% of all randomized patients in the 7 trials). The median follow-up was 6 years and was similar in all the reports.

In the survival analysis (based on 1068 deaths), simultaneous radiochemotherapy conferred an absolute survival benefit of 5.7% at 3 years (23.8% vs 18.1% for concomitant vs sequential, respectively) and 4.5% at 5 years (15.1% versus 10.6%, respectively).

Similarly, progression-free survival was better with concomitant treatment (16.0% at 3 years, 11.6% at 5 years) than with sequential treatment (13.1% at 3 years, 9.4% at 5 years).

Locoregional progression was less frequent with concomitant radiochemotherapy, but there was no significant difference between the groups in rates of distant progression (based on data from 5 trials with roughly 1100 patients).

"As expected," the authors say, "there was an increase of acute esophageal toxicity in the concomitant as compared with the sequential combination arm. However, this rate was relatively low and clinically manageable." Eighteen percent of patients who received concomitant therapy had grade 3 to 4 esophageal toxicities, compared to 4% of patients who had sequential therapy (relative risk, 4.9).

The two strategies did not differ in rates of acute grade 3 to 4 pulmonary toxicity. The researchers could not evaluate grade 3 to 4 hematologic toxicities because rates varied too widely.

"Considering the survival benefit of more than 5% at 3 years, concomitant radiochemotherapy should now be the reference treatment for locally advanced NSCLC," the authors conclude.

They add, "It is important to note that this type of treatment is generally proposed for selected, fit patients with minimal comorbidities."

J Clin Oncol 2010.