The treatment of non-small cell lung cancer: current perspectives and controversies, future directions.

The projected cure rate for patients who develop lung cancer in 1993 is only 13%. The majority of these patients have metastatic disease at the time of diagnosis, and are therefore ineligible for curative surgery. Among the minority of patients who undergo surgical therapy with curative intent, the majority experience relapse in metastatic sites. Patients with metastatic disease cannot be cured with currently available therapies. Recent randomized studies suggest that cisplatin-based chemotherapy regimens can prolong survival in patients with metastatic non-small cell lung cancer and small cell lung cancer. It was thus logical to evaluate cisplatin-based chemotherapy in early disease stages. Many randomized studies have compared radiation therapy alone with radiation plus cisplatin-based chemotherapy in locally advanced, inoperable, stages IIIA and IIIB non-small cell lung cancer. Most, but not all, of these studies show a survival benefit for the combined-modality approach. Although the improvement in median length of survival in these studies is modest, long-term survival rates are often doubled or tripled. The optimal chemoradiotherapy combination is unknown. Fewer randomized trials have evaluated cisplatin-based chemotherapy as an adjuvant to surgery in operable stages I through IIIA disease. A trial of the Lung Cancer Study Group comparing postoperative cyclophosphamide/doxorubicin/cisplatin with immunotherapy in stages II and IIIA adenocarcinoma and large cell carcinoma showed a small survival advantage for the chemotherapy. A European postoperative randomized study comparing cisplatin-based chemotherapy with no therapy also showed a survival advantage for chemotherapy, as did a small ongoing study from M.D. Anderson Cancer Center (Houston, TX) with preoperative chemotherapy. However, there are many negative randomized studies evaluating postoperative chemotherapy, especially with non-cisplatin-based regimens, and further studies are obviously needed. Many new agents have produced exciting preliminary results. Response rates in excess of 20% were reported for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), irinotecan (CPT-11), topotecan, and gemcitabine. Studies in the next few years will help to define the ultimate role of these agents. Further developments in understanding the biology (and molecular biology) of lung cancer are leading to preclinical studies of antigrowth factors and genetic therapy.