Exposure of L1210 leukemia cells first to 0.1 to 100 micromolar methotrexate and then to 10 micromolar 5-fluorouracil produces a synergistic effect on the number of cells killed in culture. Methotrexate dose-related increases occur in the concentrations of intracellular 5-fluorouracil ribonucleotides and 5-fluoro-2'-deoxyuridylate and in the incorporation of 5-fluorouracil into RNA. These increases are correlated with increased concentrations of intracellular phosphoribosylpyrophosphate. It is proposed that the enhanced formation of ribonucleotides of 5-fluorouracil and the subsequent incorporation of these compounds into RNA in methotrexate-treated cells may account for synergism between these agents.

The pattern of pulmonary involvement from ovarian cancer was evaluated in 357 patients who were seen at the Yale-New Haven Hospital from 1966 to 1975. Thoracic involvement by tumor was found in 169 patients (44.5%), a figure considerably higher than in previous reports. Pleural effusions were present in nearly 75% of patients who had thoracic involvement. Only 73% of the effusions contained identifiable malignant cells. Solid metastases to the pulmonary parenchyma were present in 12.3% of the patients; lymphangitic and nodal spread was observed in only 1% of the patients. The incidence of metastases did not correlate with tumor histologic features. Five-year survival figures were 29% for the control group; 5.6% of the patients who had evidence of thoracic involvement were alive after 5 years compared with a 49% 5-year survival of those patients with no evidence of thoracic involvement. Right-sided lesions produced thoracic metastases more frequently than left-sided lesions. No significant differences with respect to age, race, menopause, smoking history, or autopsy rate were found between those patients with and without pulmonary metastasis. Chest x-ray was found to be of great value in determining pulmonary metastasis; only 6% of patients who were proven by autopsy to have spread of cancer to the thoracic cavity had a chest x-ray that did not show malignancy. The majority of these ten patients had lymphangitic or microvascular disease. No cases of second primary occurring in the lung were noted in this review, although two case reports have appeared in the literature. Only three patients with pulmonary involvement by tumor had no other evidence of Stage IV disease.

Eighteen patients with osseous involvement were identified from a series of 124 consecutive patients treated with combined-modality therapy with advanced-stage or relapsing Hodgkin's disease. Multiple lesions were seen as frequently as were solitary lesions. Nodular sclerosing histology was as prevalent as mixed cellularity disease. However, those five cases initially diagnosed at protocol entry were predominantly mixed cellularity (80%) with multiple lesions (80%). Sites of involvement included: the spine, 24; pelvis, 8; ribs, 4; femur, 3; skull, 1; and shoulder 1. Actuarial survival for these patients was 84% at nine years. Only three patients were induction failures and no patient has had a relapse. Patients with bone lesions had favorable responses to combined-modality therapy.