Daily low-dose administrations of the chemotherapy drug carboplatin combined with radiotherapy significantly prolonged the survival of elderly lung cancer patients compared with radiotherapy alone, offering hope that the standard treatment for inoperable non-small-cell lung cancer (NSCLC) can be extended to patients ages 65 and older, according to a study published online May 22 in The Lancet Oncology.
"[Until now] evidence supporting standard treatment with concurrent chemoradiotherapy was from clinical trials in which elderly, especially frail elderly patients, were under-represented," Shinji Atagi, MD, from Kinki-chuo Chest Medical Center, Osaka, Japan, said in a release. "This trial is the first to show that combined radiotherapy can safely improve outcome of stage III NSCLC in elderly patients."
A total of 200 patients, aged 71 years or older, with inoperable NSCLC was randomly assigned chemoradiotherapy with carboplatin or radiotherapy alone. Carboplatin was used as it is known to have a more favorable toxicity profile in elderly patients. Patients were enrolled from Sept. 1, 2003, to May 27, 2010, and were tracked for a median follow-up of 19.4 months.
Results at follow-up showed that patients given the combined chemoradiotherapy treatment were nearly one-third less likely to have died than those given radiotherapy alone, with overall survival of 22.4 months and 16.9 months, respectively.
The higher toxicity of concomitant chemoradiotherapy seemingly makes the treatment unfit for elderly patients, but the low-dose carboplatin treatments in the current study were well tolerated, according to Atagi and colleagues. More than half of the chemoradiotherapy patients experienced grade 3 – 4 toxic effects, including leucopenia and neutropenia, compared with none in the radiotherapy-only group, but most infections were manageable with treatment.
“Incidence of grade 3–4 pneumonitis and late lung toxicity were similar and oesophageal toxicity was mild in both groups. Thus, additional chemotherapy did not enhance these adverse events, suggesting that combined treatment is feasible and tolerable for elderly patients with locally advanced NSCLC,” wrote the authors.
In an accompanying editorial, Juan P. Wisnivesky, MD, DrPH, of Mount Sinai School of Medicine in New York City, and Gary Strauss, MD, MPH, of Tufts Medical Center in Boston, offered some words of caution and noted that the survival advantage of concurrent chemoradiation demonstrated by Atagi et al was unexpectedly large based on the results of previous trials.
“While these findings may be due to random variability, it raises concerns about the representativeness of the sample of elderly patients enrolled in the study,” wrote Wisnivesky and Strauss. “In this case, the results of the study may not be valid to the broader population of older patients with stage III NSCLC.”
They added that they felt the study was well designed and provided “reasonably strong evidence” that chemoradiotherapy is well tolerated among elderly NSCLC patients, but physicians should be cautious in extrapolating the findings to “frail elders treated under routine care.”
Wisnivesky and Strauss wrote that additional validation of the findings would be necessary before chemoradiotherapy becomes the standard of care for the elderly.