In situ lung perfusion with cisplatin. An experimental study

BACKGROUND: This research work was planned to evaluate the soundness of in situ lung perfusion as a regional administration modality of chemotherapeutic agents. METHODS: Sixteen pigs were randomly divided into four groups and received cisplatin (2.5 mg/kg) through the pulmonary artery using one of the following techniques: stop-flow (Group 1); stop-flow/out-flow occlusion (Group 2); lung perfusion (Group 3); or lung perfusion with 5 mg/kg of infused drug (Group 4). Serial blood (carotid, pulmonary artery and vein) and tissue samples (lung and mediastinal node), were taken before, at completion of, and 5, 10, 15, 30, 60, 120, 180 and 240 minutes after cisplatin infusion for blood gas and platinum content measurement. Blood circulation was restored to the treated organ (for 60 minutes). The animals were killed, and specimens from lung, thyroid, esophagus, heart, liver, spleen, adrenal glands, kidney, bone marrow, stomach, ileum, colon, psoas muscle, and skin were obtained. Platinum concentrations in plasma, plasma ultrafiltrate (free platinum) urine, and tissues were determined by flameless atomic absorption spectroscopy. Lung damage was evaluated by light and electron microscopic examination. RESULTS: Greater systemic plasma, lower pulmonary plasma, and tissue platinum levels were detected when cisplatin was given using the stop-flow technique with respect to the other administration modalities. No significant difference in regional and systemic platinum exposure was found between Groups 2 and 3. However, lung perfusion resulted in higher mediastinal node and lower bone marrow platinum values. Morphologic alterations and impairment of gas exchanges in the treated lung were not dependent on the applied infusion technique. CONCLUSION: This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases