Inhaled Doxorubicin Active With Low Toxicity in Lung Cancer

ORLANDO—Inhaled doxorubicin has clinical activity and can be delivered without major toxicity to adults with advanced solid tumors affecting the lungs, according to a multicenter phase I study reported at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 1204).

Sunil Sharma, MD, of Memorial-Sloan Kettering Cancer Center, reported the study involving 32 patients with solid tumors, primarily sarcoma, non-small-cell lung cancer, bronchioloalveolor cancer, and mesothelioma. Twenty-four patients had received chemotherapy, and 11 had received radiation therapy.

The patients received doxorubicin hydrochloride as a sterile, pyrogen-free solution in two concentrations (16 mg/mL and 24 mg/mL) in an ethanol/water vehicle using the OncoMyst delivery device. The agent, Resmycin, was supplied by BattellePharma, Columbus, Ohio.

The treatment was given every 3 weeks for a maximum of six treatments. The amount of aerosolized doxorubicin was determined by a Tc-99m DTPA deposition test performed within 1 week prior to the first treatment.

According to Dr. Sharma, inhaled chemotherapy is optimal for reaching the alveolar areas of the lung with minimal systemic absorption. Doxorubicin is just one of various agents being studied for use with this approach.

The treatment produced one partial response at a dose level of 1.9 mg/m² in a patient with spindle cell sarcoma. "Eight of the 32 patients demonstrated stable disease at dose levels ranging from 1.5 to 3.8 mg/m²," Dr. Sharma reported.

The only observed dose-limiting toxicity was a 20% decline in FVC (forced vital capacity) following the first course in one patient. Other grade 1-2 toxicities included mainly cough, hypoxia during inhalation, loss of appetite, and light-headedness. In some patients, cough and dyspnea were already present; these symptoms worsened in some patients but improved in others with treatment. No hematologic toxicities were observed.

"The important thing about this study is that it demonstrates for the first time that you can give cytotoxic chemotherapy by inhalation and get a biological effect," Dr. Sharma said. "The technology for aerosolizing the chemotherapy and delivering it safely, reaching the alveolar areas of the lung, has only recently been developed." Inhaled doxorubicin will be further developed as therapy for bron-chioloalveolar carcinoma, in sarcomas metastatic to the lung, and as combination treatment with systemic therapy. Resmycin has received Fast Track designation by the FDA for bronchiolo alveolar carcinoma, which may allow BattellePharma to file a New Drug Application with phase II data.