Philip D. Bonomi, MD

Ganti et al have described the most recent negative lung cancer chemoprevention trial, which compared selenium to placebo.

Although improved survival is the "gold standard" for proving clinical benefit of oncologic therapy, the US Food and Drug Administration (FDA) has accepted significant results in clinical trials using surrogate endpoints as the basis for drug approval. One surrogate is the amount of tumor reduction, or tumor response. Although tumor shrinkage would seem to be a necessary precondition for improved survival, clinical studies of a variety of oncologic agents have not consistently demonstrated a correlation between the two in patients with renal cell carcinoma. Moreover, tumor response may not be an appropriate endpoint for evaluating the effects of the new targeted therapies, whose putative mechanisms are generally cytostatic rather than cytotoxic. Clinical trials suggest that some patients with other solid tumors, such as lung cancer, may derive clinical benefit from treatment that helps stabilize their disease. There is also controversy as to whether the Response Evaluation Criteria in Solid Tumors (RECIST) provides the most appropriate instrument for assessing tumor burden. Ultimately, use of a variety of endpoints as well as different trial designs may provide an adequate basis for investigating the benefits/risks of newer therapies.

Lung cancer causes more deathsin American men and womenthan the total number of deathsfrom breast, prostate, and colon cancercombined. Recently the lung cancerdeath rate has reached a plateau inthe United States, primarily because asignificant number of American menhave stopped smoking. However,smoking incidence in adult Americanwomen, as well as teenagers of bothgenders and of all ethnicities, has notdecreased significantly.

Drs. Laskin and Sandler havedone an excellent job of summarizingthe results of chemotherapyin the treatment of stageIV non–small-cell lung cancer. Theyhave pointed out that a meta-analysispublished in 1995 showed that chemotherapyprovided a modest survivaladvantage compared to supportivecare alone. In addition, they have citedstudies that have shown the treatmentis cost-effective and that it relieveslung cancer–related symptoms.They have thoroughly discussed thefact that multiple phase III trials testingnewer chemotherapy doubletsshow slightly different toxicity profiles with virtually identical efficacy,and that giving more than four coursesof therapy with regimens that consistof three or more drugs does notprovide significant benefit.

Management of disseminated non-small-cell lung cancer has changed over the past 10 years. Newer agents, such as vinorelbine (Navelbine) and paclitaxel (Taxol), have been shown to modestly improve survival in patients with

A phase III trial conducted by Eastern Cooperative Oncology Group (ECOG) investigators assessed the possible impact of paclitaxel on survival, response, and toxicity in patients with

A phase III trial conducted by Eastern Cooperative Oncology Group (ECOG) investigators assessed the possible impact of paclitaxel on survival, response, and toxicity in patients with