Inhalation chemotherapy for macroscopic primary or metastatic lung tumors:Proof of principle using dogs with spontaneously occurring tumors as a model

This study represents part of an effort to determine the safety and efficac y of inhaled antineoplastic drugs, using pet dogs with spontaneously arisin g primary and metastatic lung cancers (including sarcoma, carcinoma, and ma lignant melanoma) as a model. Dogs received new formulations of either pacl itaxel (PTX) or doxorubicin (DOX) by the inhalation route every 2 weeks usi ng a specially designed aerosol device. Response was assessed radiographica lly using the indices of tumor nodule number and volume measurement of disc rete pulmonary nodules, Dogs experiencing progressive disease after two con secutive treatments were crossed over to receive the alternate compound. In 24 dogs, 6 (25%) responses were noted including 5 partial responses (PR) a nd 1 complete response. These include 4 (22.2%) of 18 responses to DOX and 2 (13.3%) of 15 responses to PTX, Responses were noted with osteosarcoma (i ncluding three dogs with metastatic osteosarcoma that had failed prior syst emic chemotherapy), liposarcoma, hemangiosarcoma, and undifferentiated sarc oma, One dog with mammary carcinoma experienced a 47% reduction in volume a fter PTX inhalation,just shy of PR criteria. One dog with liposarcoma is ex periencing a long-term (>12 months) stabilization of disease on PTX, To dat e, no systemic toxicities have been observed with either PTX or DOX inhalat ions. Local (pulmonary) toxicity was not observed with PTX; however, change s consistent with pneumonitis/fibrosis were observed in some dogs receiving DOX, Only one of these dogs showed clinical signs, which were responsive t o steroid and antitussive therapy. These data represent "proof of principle " for the avoidance of systemic toxicity while delivering efficacious local drug levels by the inhalation route.