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.