Lung cancer is the most common cause of cancer mortality worldwide. Surgical resection is attempted for non–small-cell lung cancer when feasible, but the role of adjuvant chemotherapy has been unclear. Several randomized trials of chemotherapy have failed to show any benefit, but a recent meta-analysis of cisplatin-based chemotherapy suggested that a survival advantage was possible. The International Adjuvant Lung Cancer Trial (IALT) Collaborative Group designed a randomized trial of postsurgical chemotherapy, including cisplatin for patients with non–small-cell lung cancer, to determine if a survival benefit could be demonstrated.
To maximize enrollment and increase the statistical power of the trial to identify a survival advantage as small as 5 percent five years after treatment, the IALT protocol had few restrictions. Each participating center could decide which stages of lung cancer to include (up to stage III), which chemotherapeutic agent to include with cisplatin, and whether to offer postoperative radiotherapy in addition to chemotherapy. A total number of 1,867 patients was randomized; this number was short of the 3,300 target enrollment, chiefly because of declining enrollment later in the study when preoperative chemotherapy became more commonly employed.
Participants were randomized to receive chemotherapy within 60 days of surgery or observation alone. The median follow-up period was 56 months, and 98 percent of patients had complete data available for survival analysis. The target dosage for cisplatin (at least 240 mg per m2 of body surface area) could not be reached in 26.2 percent of patients. The most common reason this dosage could not be reached was adverse effects related to chemotherapy. Complete refusal of chemotherapy occurred in 7.8 percent of cases. Etoposide was the chemotherapeutic agent most often selected to accompany cisplatin. Postoperative radiotherapy was planned in 30.6 percent of trial subjects and was evenly distributed among the chemotherapy and observation groups via randomization.
The overall survival rate at five years was calculated to be 44.5 percent in those receiving adjuvant chemotherapy, compared with 40.4 percent in the group assigned to observation. Disease-free survival at the five-year mark was 39.4 percent in the group treated with chemotherapy and 34.3 percent in the observation group. Chemotherapy was lethal in 0.8 percent of cases and caused at least one potentially life-threatening complication (mostly neutropenia) in 22.6 percent of patients.
The authors conclude that postsurgical chemotherapy that includes cisplatin increases the five-year survival rate in patients with non–small-cell lung cancer.
editor’s note: An accompanying editorial1 describes postsurgical cisplatin as the “new standard of care” in the treatment of non–small-cell lung cancer. It is far from clear, however, whether many patients or physicians will agree that the statistical significance seen in the IALT study corresponds to clinical relevance. The small increase in survival after five years (4.1 percent) must be balanced with the 1 percent chance of death related to chemotherapy, the one-in-four chance of a life-threatening complication during treatment, and the substantial investment of time and courage needed to endure three or four cycles of chemotherapy. Observation alone still may be seen by many as a prudent option, considering the overall odds.—b.z.