ASCOAdjuvant 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
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, and 6%
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%
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
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.