Current management of unresectable non-small cell lung cancer

Historically, the standard treatment for unresectable non-small cell lung cancer was radiation therapy. Data are now accumulating, however, to indicate that combined chemotherapy and radiation therapy is superior to radiation therapy alone, although it remains uncertain whether concurrent chemotherapy with radiation therapy yields better results than a sequential approach. It is clear that surgical resection is feasible in most patients following neoadjuvant chemotherapy with or without radiation therapy, but whether surgery contributes to survival has not been established; a randomized intergroup study in stage IIIa (N2) disease addresses this question. The Southwest Oncology Group reports comparable resectability rates and survival in patients with stage IIIa and IIIb disease who received concurrent chemotherapy and radiation therapy followed by resection. Stage IV disease has traditionally been managed by supportive care alone and chemotherapy. In selected patients, statistically significant effects on survival have been seen in five randomized trials of platinum-based chemotherapy, one of which had a control arm of supportive care alone. As single agents, only carboplatin and vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) have demonstrated a survival advantage over other regimens in randomized trials, although cisplatin appears to produce similar results. Data from French studies indicate that cisplatin plus vinorelbine is superior to vindesine plus cisplatin and to vinorelbine alone. Several agents appear interesting on the basis of reported response rates in phase II trials: these include paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ), docetaxel (Taxotere; Rhoône-Poulenc Rorer, Collegeville, PA), irinotecan (CPT-II), edatrexate, and gemcitabine. Response rates are notoriously variable in this disease, however, and correlate poorly with survival effects. Randomized trials are needed to determine the value of these new agents.