ASCOAdjuvant cisplatin(Drug information on cisplatin) (Platinol)-based chemotherapy significantly improved survival in patients with completely resected non-small-cell lung cancer (NSCLC), Thierry Le Chevalier, MD, reported at the plenary session of the 39th Annual Meeting of the American Society of Clinical Oncology (abstract 6). Dr. Le Chevalier, professor of medicine, Gustav-Roussy Institute, Villejuif, France, concluded that adjuvant chemotherapy could be recommended and might prevent 7,000 deaths worldwide from NSCLC every year.
The International Adjuvant Lung Cancer Trial (IALT), which included 1,867 patients treated in 148 centers in 33 countries across five continents, showed that chemotherapy conferred a 4.1% absolute benefit in overall survival and a 5.1% absolute benefit in disease-free survival after 5 years.
IALT was designed to confirm results from the 1995 NSCLC overview meta-analysis, which suggested cisplatin-based adjuvant chemotherapy might increase the 5-year survival rate by 5% after resection, Dr. Le Chevalier said. The IALT study randomized 932 patients to adjuvant chemotherapy and 935 patients to placebo following surgery for NSCLC.
Patients in the study reflected the typical patient population with NSCLC: 80% were male with a median age of 59 years; 47% had squamous cell carcinoma, 40% had adenocarcinoma, and the rest had other types of lung cancer.
Although chemotherapy differed across treatment settings, all sites delivered cisplatin up to a total of 300 to 400 mg/m2 in three or four cycles, with 74% providing at least 240 mg/m2 of cisplatin. The drug combined with cisplatin varied by treatment sites56% used etoposide, 27% used vinorelbine (Navelbine), 11% used vinblastine(Drug information on vinblastine), and 6% used vindesine(Drug information on vindesine).
Some centers provided thoracic radiotherapy at a dose of 60 Gy based on the N stage of disease. Before entering the study, most patients in the study had undergone lobectomy (64%); 35% had pneumonectomy, and 1% segmentectomy.
More than 98% of patients enrolled in the study were still alive for follow-up in 2000. The median follow-up for the entire patient sample at the time of data analysis in September 2002 was 56 months.
Overall survival was statistically significant between the two arms of the study. Median survival was 50.8 months in the chemotherapy-treated group and 44.4 months in the placebo group. The median disease-free survival was 40.2 months among patients treated with chemotherapy vs 30.5 months among those given a placebo.
The 5-year overall survival rate, the principal objective of the study, was 44.5% in the chemotherapy arm and 40.4% in the control arm (hazard ratio, 0.86; P < .03). The 5-year disease-free survival was 39.4% in the chemotherapy group and 34.3% in the placebo group (hazard ratio, 0.83; P < .003).
In the chemotherapy arm, 23% of patients experienced at least one grade 4 toxicity, primarily neutropenia (18%), and 7 patients (0.8%) had lethal toxicity.
Data from the trial were compelling, and the study was sufficiently strong enough to provide a qualified "yes" to the question, should clinicians use adjuvant chemotherapy after resection, said discussant David Johnson, MD, director of the Division of Medical Oncology, Department of Medicine, Vanderbilt University Medical Center. "There is mounting evidence that postoperative chemotherapy benefits some patients with NSCLC," he said.
Dr. Johnson pointed out that questions nevertheless remain about how to select appropriate candidates for postoperative chemotherapy and what regimen to employ. He recommended using clinical parameters for patient selection, such as performance status, speed of postoperative recovery, number of comorbid conditions, and perhaps pathologic stage or gene profiling. It seems clear, he added, that the chemotherapeutic regimen should be platinum based.
Adjuvant chemotherapy after resection for NSCLC is "out of the gate, and the race is on to build on the provocative results from this trial," Dr. Johnson said.