The article by Walker-Renard and colleagues, although well written and researched, reaches unwarranted and misleading conclusions. The authors have, in effect, done a meta-analysis without following the rigorous procedures required for such an analysis [1].

The conclusion that "doxycycline and minocycline, with success rates of 72% and 86%, respectively, appear to be effective tetracycline-replacement agents in the few patients studied," is particularly misleading. The minocycline data are based on a sample of seven patients [2]. The total doxycycline experience of 60 patients from three trials showed only a 10% response to the first dose of doxycycline as noted in Table 1 of their manuscript. This is critical when one of the reasons for dismissing bleomycin as the current agent of choice is its cost. Bleomycin was found to be superior to tetracycline in the only randomized trial for treatment of malignant pleural effusions [3], and its cost, as noted in their Table 3, is approximately $1000, although the recommended dose is 60 units rather than 1 unit/kg, which would give a dose of 70 units for the "average" 70-kg patient [3]. If 90% of patients require several days in the hospital to obtain a response (with doxycycline doses given at least 1 day apart to assess response), the cost will rapidly exceed that of one dose of bleomycin. In addition, the use of soft catheters in the ambulatory setting instead of hospitalization for chest tube placement is not feasible if multiple doses are required [4].

Talc is the agent with the highest response rate to date, but until recently it was given in the operating room through insufflation. The costs of anesthesia, surgery, and several days of hospitalization far exceed the cost of one dose of bleomycin, even in those patients who can tolerate an operation [5]. The technique of using a talc slurry through a chest tube also shows promise but has suffered from the absence of available material in a sterile form and has not been tested in a randomized trial. Critical to any discussion of health care costs is inclusion of the entire episode of care, not just the cost of one component.

A National Cancer Institute intergroup trial will soon compare intrapleural talc (5 g through slurry), bleomycin (60 units), and doxycycline (500 mg). Until the completion of the trial, we will have no accurate data on the relative merits of talc slurry and doxycycline. This trial will address costs by recording the number of hospital days plus the need for any re-treatment at the time of recurrence. In the interim, we recommend the use of bleomycin, which has been recently approved by the Food and Drug Administration Advisory Committee for the management of malignant pleural effusions.