Adding daily low-dose carboplatin chemotherapy to thoracic radiotherapy significantly extended survival in elderly patients with unresectable locally advanced non–small cell lung cancer, according to a study published online May 22 in the Lancet Oncology.
Investigators from the Japan Clinical Oncology Group reported a phase III trial was stopped early after a planned interim analysis showed a 5.5 month gain in median overall survival when this combination was compared with radiotherapy alone.
The addition of low-dose carboplatin did not increase pneumonitis, lung toxicity, or esophageal toxicity; it did increase hematologic toxicity and infections, but these "were manageable with appropriate treatment." Thus, this chemoradiotherapy "is feasible and tolerable for elderly patients with locally advanced" non–small cell lung cancer (NSCLC), and clinicians should consider it, said Dr. Shinji Atagi of the department of thoracic oncology, Kinki-Chuo Chest Medical Center, Osaka, Japan, and his associates.
"This trial is, to the best of our knowledge, the first study to show that combined chemoradiotherapy can improve the outcome of stage III NSCLC in elderly patients," they noted.
The median patient age was 77 years (range 71-93 years), and "the two groups were well-balanced with respect to sex, performance status, and disease and tumor stage," the investigators said. Approximately 80% of the cohort were men, and 90% had a history of smoking.
The appropriate treatment for elderly patients with stage III NSCLC is controversial because few clinical trials have addressed the standard chemoradiotherapy approach specifically in this age group. As cisplatin is considered to be contraindicated in most elderly patients because of its high toxicity, Dr. Atagi and his colleagues assessed a less-toxic analogue, low-dose carboplatin, in the multicenter phase III clinical trial (JCOG0301).
The trial recruited 200 patients aged 71 years or older who had unresectable stage IIIA or IIIB disease and had received no previous chemotherapy or radiotherapy. Participants were randomly assigned to receive 60 Gy of radiotherapy alone (100 patients) in 30 fractions or 60 Gy of radiotherapy in 30 fractions plus a daily 30-minute 30 mg/m2 IV infusion of carboplatin (100 patients) 1 hour before the first 20 fractions. Both patients and clinicians were unblinded to treatment assignment.
A planned interim analysis of the data 10 months after patient enrollment was completed, when the median length of follow-up was 19 months, showed that survival was clearly superior with the combined treatment. So the trial was halted early (Lancet Oncol. 2012 [doi:10.1016/S1470-2045(12)70139-0).
At that time, median progression-free survival was 8.9 months with chemoradiotherapy, significantly longer than the 6.8-month progression-free survival with radiotherapy alone.
Median overall survival was 22.4 months with chemoradiotherapy, significantly longer than the 16.9-month overall survival with radiotherapy alone.
The 1-year survival was 70.8% with chemoradiotherapy, compared with 65.2% with radiotherapy alone. The 2-year survival was 46.3% with chemoradiotherapy, compared with 35.1% with radiotherapy alone. These differences also were statistically significant.
At the time of this analysis, 74.7% of the patients in the chemoradiotherapy group showed disease progression, compared with 83.7% of patients in the radiotherapy only group. The sites of recurrence were similar between the two groups.
More patients in the chemoradiotherapy group developed leukopenia, neutropenia, or thrombocytopenia. Grade 4 leukopenia developed in 12 patients and grade 4 neutropenia in 22 patients in the combined-therapy group, compared with 0 patients in the radiotherapy only group. The incidence of grade 3 infections also was higher with chemoradiotherapy.
Investigators reported seven treatment-related deaths: three with chemoradiotherapy and four with radiotherapy.
This study was funded by the Ministry of Health, Labour, and Welfare of Japan. No financial conflicts of interest were reported.