New drugs in the treatment of non-small cell lung cancer.
Non-small cell lung cancer accounts for 75% of all lung tumours, and only about 10% of patients will remain alive 5 years after diagnosis. Few cytotoxic drugs currently registered produce more than a 15% response rate as a single agent or 30%-35% in combination, with only modest survival benefits. New cytotoxic drugs entering phase II and III studies, however, appear to have more than 20% activity against this disease. They include the taxanes (taxol and taxotere), camptothecin analogues (CPT-11 and topotecan), antimetabolites (edatrexate and gemcitabine) and the vinca alkaloid, navelbine. Taxol produces response rates of about 25% in previously untreated patients and is currently undergoing trials at higher doses in combination with cisplatin and granulocyte colony-stimulating factor. Taxotere produces response rates of 33% in previously untreated patients and 21% in patients previously refractory to platinum-containing regimens. The camptothecin analogues, which are inhibitors of topoisomerase I, may produce response rates of up to 41% in previously untreated patients, but these results have varied considerably between different trials (response rates as low as 13.5% have been reported for topotecan). A phase II study with edatrexate produced a response rate of 32% but subsequent trials using combination chemotherapy including this agent have been disappointing. The activity of gemcitabine as a single agent is 20%-25%. Three ongoing phase II studies combining cisplatin and gemcitabine have shown response rates of up to 50%. Gemcitabine has minimal subjective toxicity. Navelbine produces response rates of 22%-33% as a single agent and up to 65% in combination. These new cytotoxic agents with significant activity in non-small cell lung cancer provide exciting potential for developing novel combination regimens in the advanced setting and as neoadjuvant and adjuvant therapy.
Steward
W P
WP
NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.
Dunlop
D J
DJ
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine; D002166:Camptothecin