© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 8, 556,
April 17, 2002
© 2002 Oxford University Press
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Aerosolized Chemotherapy? Inhalation Therapy Gains Ground
Delivering chemotherapy intravenously is still the most common method of drug delivery, but inhalation therapy is being explored as a way to deliver chemotherapy drugs directly to the lungs, either for a primary cancer or cancer that has spread to the lungs.
At the 12th International Congress on Anti-Cancer Treatment, which was held in Paris earlier this year, Edith Huland, M.D., of the University of Hamburg, Germany, presented 12 years’ worth of data on treating lung metastases from renal cell carcinoma with interleukin 2.
At their clinic, patients receive 90% of the IL-2 dose by inhalation and 10% by subcutaneous injection. She said there was a complete or partial response in 30% of patients, and the disease stabilized in 50% of patients. "In about 65% [of patients] it is possible to control the disease for about 3 months, and maybe even longer," she said.
Some patients experienced some throat irritation, but there was no evidence of severe, acute, or chronic toxicity, Huland said. In clinical trials of IL-2 delivered by inhalation, a dose-dependent cough is the most common adverse event.
In the United States, Battelle Pulmonary Therapeutics, Columbus, Ohio, has developed a doxorubicin inhalation therapy for bronchioalveolar carcinoma, which has been given fast track status by the U.S. Food and Drug Administration. The company also recently received a patent to cover a method for treating lung cancer by inhalation.
"We are extremely hopeful that we will be able to achieve levels of the drug in the lungs which far exceed that obtainable by IV delivery," said Anthony R Imondi, Ph.D., vice president of regulatory and clinical affairs for Battelle Pulmonary Therapeutics.
There is a phase I study of the doxorubicin therapy under way for patients with lung cancer or cancer that has spread to the lungs. Participants will receive one dose of doxorubicin every 3 weeks for a total of three doses in 9 weeks. Patients inhale the drug through a mouthpiece on a special machine.
The delivery of morphine directly into the lung by inhalation was also the subject of reports at the recent American Pain Society meeting, held in Baltimore.
A new delivery technology developed by the Aradigm Corp., Hayward, Calif., has been tested in about 100 patients to deliver aerosolized morphine directly into the lung for acute or breakthrough pain.
"Our patients were quite pleased with the rapid onset of pain relief," said Neal Slatkin, M.D., City of Hope Medical Center in Duarte, Calif., and one of the investigators.
John Thipphawong, M.D., Aradigm’s medical director, showed that, in 16 patients with advanced cancer pain, there was quicker relief in the first 15 minutes with the new system than with oral release morphine. In another study in 89 post-surgery patients, pain relief after three inhalations of morphine was comparable to that of 4 mg of intravenous morphine, he said.
All of the studies share the same goal of delivering drugs directly to the site of disease. A potential advantage of inhalation therapy is a decrease in the amount of drug needed to provide the same effect as systemic therapy. However, questions such as what the best delivery method is and what the best chemotherapy drugs to use still need to be answered.
Regardless, the ease of delivery and the direct targeting make inhalation therapy an attractive technology, concluded Sunil Sharma, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues in a review article in the Journal of Clinical Oncology. Researchers will also have to determine which patients are most appropriate for such therapy.
"Like most regional therapies, inhalational therapies will be most useful in selected situations, probably as an adjuvant treatment in individuals at high risk for pulmonary metastases or in combination with systemic therapies in which pulmonary tumors present special difficulties," they wrote.
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