Frank V. Fossella, MD

The novel multitargeted antimetabolite pemetrexed (Alimta), recentlyapproved by the US Food and Drug Administration for the treatment ofmesothelioma when combined with cisplatin, is also active in first- andsecond-line non–small-cell lung cancer (NSCLC). In a phase III trialcomparing single-agent pemetrexed vs docetaxel (Taxotere) as secondlinetherapy in advanced NSCLC, survival was shown to be comparablebetween these agents, but side effects were significantly less frequentand severe for patients who received pemetrexed. In the frontlinesetting, phase II studies have shown significant activity and a veryfavorable toxicity profile of the combination of pemetrexed with a platinumagent. Pemetrexed has been well tolerated at systemic doses as aradiosensitizer when given as concurrent chest radiation, and a phaseI study is under way to assess its tolerability in combination withcarboplatin (Paraplatin) in this setting. Pemetrexed is an importantaddition to the armamentarium of medicines used to treat thoracicmalignancies, and merits study in combination with other drugs havingnovel mechanisms of action.

Two phase III trials were conducted using docetaxel (Taxotere), administered every 3 weeks, as second-line treatment of non-small-cell lung cancer (NSCLC) in patients previously treated with platinum-based chemotherapy. In the TAX 317 trial, 204 patients were randomized to receive either docetaxel (49 received 100 mg/m² and 55 received 75 mg/m²) or best supportive care (100 patients). Median survival was 7.5 months with docetaxel at 75 mg/m² (D75) vs 4.6 months for best supportive care (P = .010); and 1-year survival was 37% for D75 vs 11% for best supportive care (P = .010).

There are few options availablefor the patient with advanced non-small-cell lung cancer in whom first-linechemotherapy has failed. Docetaxel (Taxotere), a semisynthetic taxoid,is one of the few drugs that has been systematically investigated as asecond-line option for patients with advanced non-small-cell lung cancer.