NEW YORK (Reuters Health) Dec 24 - For limited-stage small-cell lung cancer (SCLC), four cycles of etoposide plus cisplatin and accelerated hyperfractionated thoracic radiotherapy (AHTRT) should remain the standard of care, new research from Japan suggests.
For extensive-stage SCLC, though, irinotecan plus cisplatin significantly improves overall survival, compared with etoposide plus cisplatin, the authors wrote online December 3 in The Lancet Oncology.
"It is important to understand that one-third of patients with limited-stage SCLC can be cured by the standard four cycles of etoposide plus cisplatin and AHTRT," said lead author Dr. Kaoru Kubota of Nippon Medical School in Tokyo, Japan, in email to Reuters Health.
"While the excellent five-year overall survival of 34.3% for all patients who entered into the study is surprising," the negative results of irinotecan plus cisplatin were not, "because irinotecan plus plantinum for stage III non-small cell lung cancer is no better than other regimens," he added.
The data are from a phase III trial conducted in 281 patients with previously untreated limited-stage SCLC at 36 institutions in Japan.
Patients ages 20 to 70, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and adequate organ function, received IV etoposide 100 mg/m² on days 1 through 3 and IV cisplatin 80 mg/m² on day 1, plus AHTRT (1.5 Gray twice a day, 5 days a week, for a total 45 Gray over 3 weeks).
Patients without progressive disease after induction therapy were randomized in a 1:1 ratio to receive three more cycles of etoposide plus cisplatin, or irinotecan plus cisplatin (IV irinotecan 60 mg/m² on days 1, 8, and 15; IV cisplatin 60 mg/m² on day 1).
The median overall survival in the etoposide-plus-cisplatin group was 3.2 years, compared with 2.8 years in the irinotecan and cisplatin group (hazard ratio 1.09; one-sided stratified log-rank p=0.70).
Adverse events of grade 3 or 4 included neutropenia (95% vs 78% in the etoposide-plus-cisplatin vs the irinotecan-plus-cisplatin groups, respectively), anemia (35% vs 39%), thrombocytopenia (21% vs 5%), febrile neutropenia (17% vs 14%), and diarrhea (2% vs 10%).
One treatment-related adverse event ended in death in each group: radiation pneumonitis in the etoposide-plus-cisplatin group, and brain infarction in the irinotecan-plus-cisplatin group.
"I would like to stress the importance of supportive care and on the communication skills needed in breaking bad news to patients. We fully disclosed the prognosis in the consent form for the study and we did not interrupt radiotherapy when neutropenia occurred," Dr. Kubota said.
"We should do our best to encourage our patients and other people to quit smoking," he advised.
Dr. Gregory Peter Kalemkerian, professor of medical oncology at the University of Michigan in Ann Arbor, whose editorial accompanied the paper, told Reuters Health that "the bulk of the evidence suggests that there is not much difference between these two regimens from an efficacy standpoint; it's mainly a toxicity issue. The drug toxicities differ, and most of us view irinotecan as a more toxic drug than etoposide."
"This study highlights that, despite the fact that we want to move forward and do something different and better, we're still unfortunately utilizing platinum and etoposide as the standard treatment in small-cell lung cancer. This treatment has benefits, but it's not as good as we want it to be. Many strategies have been utilized, but none seem to be better than what we've been using for the past 25 to 30 years," he said.
"We have to keep doing studies to learn more about the genetic aspects of what's driving small-cell lung cancer and keep working to find better, more effective, and more targeted ways of killing the disease," he said.
The study was supported by the National Cancer Center and the Ministry of Health, Labor and Welfare of Japan.
SOURCE: http://bit.ly/1kDt76x
Lancet Oncology 2013.
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