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Biomedical subjects

F M Muggia

Publications and source records attributed to F M Muggia.

At least 271 records · Page 15Linked to original sources

5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia.

Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.

Animals↗

Cyclophosphamide and CCNU in the treatment of inoperable small cell carcinoma and adenocarcinoma of the lung.

Two hundred and fifty-eight patients with small cell carcinoma and 185 patients with adenocarcinoma were centrally randomized to receive either cyclophosphamide (1000 mg/m2 every 3 weeks) iv or cyclophosphamide (700 mg/m2 every 3 weeks) iv plus CCNU (70 mg/m2 every 6 weeks) orally. Those patients who were initially treated with the single agent were then treated with CCNU (130 mg/m2 every 6 weeks) at the time of cyclophosphamide failure. Objective tumor regression occurred more frequently with the combination regimen in patients with small cell carcinoma (43% vs 22%, P = 0.002), but no difference in response rates was apparent in patients with adenocarcinoma. In both cell types patients survived somewhat longer following treatment with the combination. The overall incidence of severe toxicity was equal for the two regimens in both cell types; however, the therapeutic index of the combination was superior to that of the single agent in small cell carcinoma. Severe drug toxicity was more frequent in small cell carcinoma patients with extensive disease, and survival was reduced in both cell types with extensive disease. Survival was better for ambulatory patients in both cell types and women survived longer than men. In women with small cell carcinoma, ambulatory status also was associated with a higher incidence of tumor regression. In patients with small cell carcinoma those who had prior lung surgery survived longer than those without prior surgery. Previous radiation therapy was associated with a reduced incidence of objective regression in men with small cell carcinoma. In both cell types patients with tumor regression lived longer than nonresponders; however, objective disease stability was associated with improved survival only in patients with adenocarcinoma. Stratification in future studies should consider extent of disease, performance status, sex, and prior therapy.

Adenocarcinoma↗

Ectopic placental proteins in nontrophoblastic tumors. Serial measurements following chemotherapy.

Four men with metastatic carcinoma (two bronchus, one stomach, one primary unknown) and ectopic placental protein production (one chorionic gonadotropin (hCG and its alpha subunit; one placental lactogen (hPL); one hCG alone; one hCG and hPL) were studied with serial retrospective measurements of the ectopic protein concentrations in serum, correlated with objective assessment of clinical status. The biochemical marker and clinical response were documented during treatment with a variety of agents and during periods without therapy. Of nine assessable periods, seven showed concordance of biochemical marker and clinical responses.

Antineoplastic Agents↗

Irradiated lung cancer. An autopsy analysis of spread pattern.

The spread pattern was studied in 48 autopsied cases of irradiated, apparently localized lung cancer. Disease was found in the upper abdomen in 52%, in the brain in 8.7%; in the bones in 20.8%; and confined to the thoracic cavity in 27%. Radical irradiation controlled 38% locally. The pattern of metastasis in these irradiated lung tumors did not seem to differ from that of unirradiated lung cancers reported elsewhere.

Adenocarcinoma↗

Radiation-related eosinophilia. Correlation with delayed hypersensitivity, lymphocyte count, and survival in patients treated by curative radiotherapy.

Abdominal irradiation may produce eosinophilia. The relationship between radiation-related eosinophilia (RRE), reactivity to 2-4 dinitrochlorobenzene (DNCB), lymphocyte count, and prognosis was evaluated in 98 patients irradiated for tumors below the diaphragm. Forty-two per cent manifested RRE and 62% reacted to DNCB. Fifteen of 19 (79%) reactors who had RRE were disease-free at 6 months. Fourteen of 22 (64%) nonreactors who had RRE and 26 of 42 (62%) DNCB reactors without RRE were controlled. Fourteen of 15 (93%) nonreactors without RRE had disease at 6 months. Those who had RRE had double the median survival of those who did not.

Abdominal Neoplasms↗

Cell kinetic studies in patients with lung cancer.

Widespread application of intralesional tritiated thymidine injection to obtain cell kinetic data in lung cancer is described. Thymidine-labeling indices were obtained in 28 patients with lung cancer, and the data analyzed by histologic cell types. The mean and median labeling indices were highest in small-cell carcinoma of the lung. Mean values were significantly higher in the small-cell and in the large-cell undifferentiated carcinoma groups than in the adenocarcinoma and epidermoid carcinoma. On the other hand, a labeled mitosis curve in a patient with small-cell carcinoma yielded a duration of DNA synthesis of 18.8 h; not unlike those obtained for other solid tumors. According to our concepts of tumor growth, these findings suggest that the fraction of proliferating cells may be significantly higher in the small-cell and large-cell undifferentiated carcinomas than in the more differentiated cell types of bronchogenic cancer. Knowledge of the growth fraction of these cancers may have implications in directing therapeutic approaches and in interpreting features of the natural history of the disease.

Adenocarcinoma↗