Three hours after the intravenous infusion of doxorubicin (3 mg/kg over 15 min) to anesthetized dogs, the drug concentration was found much higher in the myocardium than in the plasma (about 4,000 ng/g, i.e., 50 times higher). After the intravenous infusion of doxorubicin (1.5 mg/kg over 15 min) to conscious dogs, the drug concentration appeared to decline very slowly in the myocardium, since it was close to 200 ng/g at the 7th day, whereas the plasma concentration had fallen to zero, and the drug was still detected in the cardiac tissue 21 days after the administration. As myocardial concentrations of doxorubicin persist long after plasma clearance is complete, the hazards of repeated administration, based on plasma kinetic patterns, must be emphasized.
Among the patients showing evidence of cerebral metastases without previously known cancer history, lung cancer has been found 37 times as the primary tumor in our institution. There were 34 men and three women and all but two were heavy smokers. Only one presented at diagnosis with thoracic symptoms but the chest radiograph was abnormal in 34. The histologic type of the primary tumor was obtained in 32 cases as a result of thoracic investigations and in five cases from metastatic tumor tissue. The primary tumor appeared to be non-small cell lung carcinoma in 26 cases and small cell lung carcinoma in 11 cases. These results show that patients treated with surgery (20 cases) have a better survival (median 10 months versus 4.5) than the others, and among surgically treated patients only those treated with bifocal resection (eight patients) are long-term survivors. Also, in four of six patients, objective regression of the neurologic symptoms was seen after radiation therapy alone. Central nervous system relapse was seen in 12 patients, but in none of the patients treated with postoperative radiation therapy. Conventional chemotherapy (11 patients) induced objective responses only in the small cell type and proved to be too toxic when used simultaneously with radiation therapy in inoperable patients.
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