Lancet: Chemo + radiotherapy efficacious for late-stage NSCLC

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Radiotherapy plus chemotherapy, with or without surgery, are both treatment options for patients with stage IIIA (N2) non-small cell lung cancer (NSCLC), according to research published online July 26 in Lancet.

NSCLC makes up some 80 percent of lung cancers, and its most common cause is long-term exposure to tobacco smoke, the authors wrote.

In this phase III, randomized controlled trial, Kathy Albain, MD, Loyola University Chicago Stritch School of Medicine in Maywood, Ill., and colleagues compared concurrent chemotherapy and radiotherapy followed by surgery with standard concurrent chemotherapy and radiotherapy without surgery--the latter of which is the current standard for this patient group.

The researchers randomly assigned patients with stage IIIA (N2) NSCLC to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m2 on days 1, 8, 29 and 36] and etoposide [50 mg/m2 on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals.

If they found no progression, patients in Group One underwent surgery, and those in Group Two continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups.

Overall, 202 patients (median age 59 years, range 31-77) were assigned to Group One and 194 (61 years, 32-78) to Group Two. The authors noted that the primary endpoint was overall survival.

Albain and colleagues reported that median overall survival was 23.6 months in Group One, compared with 22.2 months in Group Two--a non-statistically significant difference.

The researchers reported that the number of patients alive at five years was 37 in Group One and 24 in Group Two. Progression free survival seemed better in Group One than in Group Two, median 12.8 months versus 10.5 months; the number of patients without disease progression at five years was 32 (Group One) versus 13 (Group Two).

Lower white blood cell counts and esophagitis were the main grade three or four toxicities associated with chemotherapy plus radiotherapy in Group One (38 percent and 10 percent, respectively) and Group Two (41 percent and 23 percent, respectively), according to the investigators. In Group One, 8 percent deaths were treatment related versus 2 percent Group Two. In an exploratory analysis, overall survival was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy.

The authors suggested the reason for an absence of effect of surgery could be inadequate power in the trial or reduced delivery of later chemotherapy (cycles three and four) in the surgery group. However, they said that the most likely reason could be increased mortality following pneumonectomy, mainly due to acute respiratory distress syndrome and other respiratory causes.

"Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA (N2) non-small-cell lung cancer... medically healthy patients with stage IIIA (N2) non-small-cell lung cancer should be assessed by a team skilled in multimodality treatment, and treatment options can be considered during assessment," the authors wrote. "On the basis of the findings of our study, patients should be counseled about the risks and potential benefits of definitive chemotherapy plus radiotherapy with and without a surgical resection (preferably by lobectomy)."

In an accompanying commentary, Wilfried E. E. Eberhardt, MD, West German Tumour Centre, University Hospital Essen of the University Duisburg-Essen in Essen, Germany, and colleagues said: "Can we undertake surgery in patients with stage IIIA (N2) NSCLC after induction chemoradiotherapy from now on? Yes, we can-selectively in patients with less extensive resection (eg, lobectomy) than pneumonectomy."