In an article likely to spark controversy, researchers at the prestigious Memorial Sloan-Kettering Cancer Center in New York City have called for curtailed use of aerosol pentamidine, a widespread experimental therapy for a pneumonia that afflicts AIDS patients.
"Aerosol pentamidine should not be used for treatment of pneumocystis pneumonia and should be used as (a preventive measure) only in careful clinical trials," Dr. Donald Armstrong and Ed Bernard wrote in an editorial published in today's issue of the Annals of Internal Medicine.
Widely regarded as a promising therapy against pneumocystis carinii pneumonia, aerosol pentamidine is believed to be used by thousands of AIDS patients, either in controlled clinical trials or under the supervision of their personal physicians.
Pressure on FDA
Some AIDS specialists as well as patient advocacy groups have pressed the federal Food and Drug Administration to make the aerosol drug even more widely available. Pneumocystis pneumonia is the first sign of acquired immune deficiency syndrome in about three-fifths of all AIDS patients and a common cause of death.
The widely held view that it is helpful is disputed in part by the Sloan-Kettering researchers. While acknowledging preliminary data that the aerosol treatments appear to decrease by about tenfold the incidence of recurrence of pneumocystis in patients who are administered the drug after they have recovered from one bout of the disease, the researchers recommend that the aerosol not even be tested as a therapy for active cases of the pneumonia. They cite a failure rate in one 13-patient British study of more than 75%.
"Our experience in treating mild episodes of this infection with conventional therapy (antibiotics injected through a vein) indicates that these failures and deaths (with aerosol pentamidine) should not have occurred," their editorial states.
These recommendations were criticized as premature and unwarranted by Dr. A. Bruce Montgomery, assistant professor of medicine at the State University of New York at Stony Brook and the principal investigator in an ongoing nationwide study that compares aerosol pentamidine therapy for the pneumonia to conventional intravenous therapy.
In addition, the editorial does not disclose a financial relationship between the Sloan-Kettering researchers and Fisons Corp. of Bedford, Mass, one of two drug companies competing for the potentially lucrative right to market the drug in the United States. Montgomery's treatment study is funded by the other drug company, LyphoMed Inc. of Rosemont, Ill.
'Doing a Good Trial'
"The only way this is going to be settled is with good trials, and I am doing a good trial," Montgomery said in a telephone interview. "The data was presented to the Data Safety Monitoring Board at the National Institute of Allergy and Infectious Diseases on Nov. 14, and they saw no difficulty in continuing the study. Representatives of the FDA were present as well."
Montgomery said that, so far, the overall mortality in the trial is less than 10% and in no cases has the disease spread to other organs. He said the British research, cited in the editorial, showed a high percentage of treatment failures because the aerosol pentamidine had not been administered correctly. Montgomery said he has subsequently helped the physicians at the Middlesex Hospital Medical School in London learn to use the therapy correctly. As a result, their failure rate has dramatically declined.
Pneumocystis pneumonia has been conventionally treated by injecting antibiotics directly into the bloodstream. The two leading medications, both of which are approved for prescription use, are intravenous pentamidine and oral or intravenous trimethoprim-sulfamethoxazole.
In AIDS patients, administration of these medications is often accompanied by adverse side effects. Many individuals have to change medicines or stop their treatment entirely.
Fewer Side Effects
For most patients, the experimental aerosol treatments appear to have far fewer side effects than the conventional therapies. They are given by dissolving pentamidine powder designed for intravenous administration in sterile water. The patient then inhales the medicine through an inexpensive device that disperses the medication into a fine mist.
To treat the pneumonia, aerosol treatments are given once a day for three weeks. Experimental preventive treatments are repeated at intervals ranging from weekly to monthly.
The editorial says the aerosol therapy should only be used to treat pneumocystis patients if a conventional drug is used as well. It cites problems with getting the inhaled drug into the diseased parts of the lungs and the potential for the pneumocystis infection to spread.
The researchers said they were aware of 21 such cases of disseminated disease that have been reported in medical journals; by contrast tens of thousands of AIDS patients have had pneumocystis infections confined to their lungs.
Montgomery's study, which is also funded by the National Institutes of Health, has enrolled 180 of a projected 240 patients. It is being conducted at 22 medical centers nationwide, including Harbor-UCLA, County-USC and St. Mary Medical Center in Long Beach. The results are expected to be available in mid-1989.
Asked if their editorial could be interpreted as a self-interested criticism of a competitor's research, Armstrong, the chief of infectious diseases at Sloan-Kettering, said: "That has nothing to do with it. . . . That really doesn't influence my reasoning."