Serum cholesterol, beta-carotene, and risk of lung cancer.

This paper hypothesizes that beta-carotene mediates the association between low serum cholesterol and increased risk of lung cancer, predicts that the association should be greater in population strata with low intake of beta-carotene than in those with high intake if the hypothesis is correct, and investigates this prediction with data from a 24-year cohort study of 1,960 middle-aged employed men. In the total cohort, serum cholesterol was not related to risk of lung cancer. The relative risk associated with a difference of -1.0 mmol per liter in serum cholesterol was 1.01 (95% confidence interval of 0.80-1.27) after adjustment for cigarette smoking, age, and intake of beta-carotene. In contrast, however, when the study group was restricted to men with intake of beta-carotene less than 5,000 (N = 929) or less than 3,000 IU per day (N = 272), comparable relative risks were 1.10 and 1.21, respectively. Although the 95% confidence intervals for these relative risks were broad and included unity, the result is consistent with expectation. We conclude that the hypothesis warrants further investigation.

Dietary cholesterol and incidence of lung cancer: the Western Electric Study.

The hypothesis that dietary cholesterol is positively associated with lung cancer was investigated in a 24-year cohort study of 1,878 middle-aged men who were employed in 1958 by the Western Electric Company in Chicago. The relative risk of lung cancer associated with an increment in dietary cholesterol of 500 mg/day was 1.9 (95 percent confidence interval 1.1-3.4) after adjustment for cigarettes, age, and intake of beta-carotene and fat. Results suggested that the association was specific to cholesterol from eggs. Further research is needed to understand the basis for this association.

Phase II trial of 4' deoxydoxorubicin (DXDX) for unresectable non-small cell bronchogenic carcinoma. An Illinois Cancer Council study.

A phase II trial of 4' Deoxydoxorubicin (DXDX) was conducted in unresectable previously untreated non-small cell lung cancer patients. DXDX was administered every 3 weeks by short intravenous infusion at a starting dose of 30 mg/m2, with dose escalation to 40 mg/m2 toxicity permitting. Four responses, all partial, were observed in 35 evaluable patients, for a response rate of 11% (95% confidence limits 3.2% and 26.7%). Myelosuppression was the dose-limiting toxicity. Cardiotoxicity was not seen. DXDX has minimal activity against non-small cell lung cancer as a single agent at the dosage used in this study.

Megestrol acetate used as primary hormonal therapy in stage D prostatic cancer.

The majority of patients with advanced prostatic cancer respond either to castration or estrogen therapy. In an attempt to identify an alternative hormonal therapy, 25 symptomatic stage D prostate cancer patients were treated with megestrol acetate as initial hormonal therapy. Thirty-three patients were evaluable for response as defined by the National Prostatic Cancer Project criteria. Partial remission was observed in 11 patients and stable disease in 5, with an overall response rate of 70%. The projected median duration of response and survival were 10 and 20 months, respectively. Weight gain was common, but only two patients showed evidence of fluid retention. Gynecomastia, thromboembolic episodes, and gastrointestinal side effects were not observed in this group of patients, though two patients had increased pain shortly after therapy was initiated. Thus, in advanced prostatic cancer, megestrol acetate is effective primary therapy with minimal side effects.

Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men.

Mortality rates from colon cancer in the USA are highest in populations exposed to the least amounts of natural sunlight; differences in endogenous vitamin D production and calcium absorption could be responsible. To investigate this possibility, the association of dietary vitamin D and calcium with 19-year risk of colorectal cancer was examined in 1954 men who had completed detailed, 28-day dietary histories in the period 1957-59. Risk of colorectal cancer was inversely correlated with dietary vitamin D and calcium. In the quartiles of a combined index of dietary vitamin D and calcium, from lowest to highest, observed risks of colorectal cancer were 38.9, 24.5, 22.5, and 14.3/1000 population. This association remained significant after adjustment for age, daily cigarette consumption, body mass index, ethanol consumption, and percentage of calories obtained from fat.

Progesterone receptor level as a predictor of response to megestrol acetate in advanced breast cancer: a retrospective study.

Megestrol acetate (160 mg/day) produced a response rate of 44% in a retrospective series of 39 evaluable patients with advanced breast cancer. The estrogen-receptor (ER) level was greater than 10 fmols/mg of protein in 28 patients, and the progesterone-receptor (PR) level was greater than 10 fmols/mg of protein in 26 patients. ER and PR levels, age, and disease-free interval were analyzed for their relationship to response. The PR was the single best predictor of response to megestrol acetate; the addition of ER added 2% to the predictive accuracy rate of PR alone.

The role of the human tumor stem cell assay in medical oncology.

The human tumor stem cell assay is a technique that allows in vitro sensitivity testing of antineoplastic agents against cells from tumor specimens removed from patients. This assay predicts clinical response to drugs and permits individualization of chemotherapy. It is more accurate in predicting drug resistance than drug sensitivity. Although there are technical problems with the assay, it has been successfully applied to nearly every possible type of human solid tumor and can be performed using cells from malignant effusions as well. Screening of new agents for activity against a range of human tumor specimens may prove to be the most important application of the human tumor stem cell assay.

Randomized evaluation of combination chemotherapy vs. observation alone following response or stabilization after oophorectomy for metastatic breast cancer in premenopausal women.

Premenopausal patients with progressive measurable metastatic breast cancer who demonstrated either stable or responsive disease 12 weeks following oophorectomy were randomized either to receive cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) combination chemo-therapy (20 patients) or to continue under observation alone (14 patients). Since the study began in 1974, data on receptor status were not required for entry into the study. Stratification for randomization was based on the nature of the oophorectomy response (stable vs. response), dominant metastatic site (visceral vs. osseous vs. soft tissue), and disease-free interval (greater than 2 years vs. lesser than 2 years). Three (21%) of the 14 patients under observation alone continued to improve whereas 6 of 18 (33%) of the patients given CMF improved further, an insignificant difference. The median time to failure from oophorectomy was 17.5 months for the CMF group and 6.1 months for the observation group (p = 0.01). Using a multivariate proportional hazards model, visceral disease (p = 0.05) and breast involvement (p = 0.001) were also associated with significantly shorter times to failure. After the randomization, the fraction of observation patients progressing within 8 weeks was significantly greater than that of the CMF patients (5/14 vs. 0/21, p = 0.01). With 9 of the 14 observation patients and 11 of the 20 CMF patients dead, the estimated median survivals are similar at 40.4 and 41.3 months, respectively. We conclude that the addition of CMF chemotherapy to patients with stable-disease or objective response following oophorectomy significantly increases the median duration to treatment failure, whereas there appears to be no survival advantage for such therapy.

Vindesine: phase II evaluation in colon cancer and description of its platelet stimulating activity.

Fifteen previously treated patients with measurable metastatic colon carcinoma were entered into a phase II study of vindesine, 3 mg/m2/week IV. Fourteen patients were evaluable for response. No objective tumor response was observed; however, seven patients experienced stable disease lasting 9, 10, 13, 15, 16, 19, and 26 weeks. Neurologic toxicity was the most common nonhematologic side-effect noted, manifesting as abdominal pain, constipation, paralytic ileus, or paresthesias. Leukopenia was observed in 16% of the 104 weekly courses. Nine patients had a 50% increase of their platelet counts above their pretreatment platelet counts; six patients had a doubling of their pretreatment platelet counts. Mean platelet counts revealed a linear increase with successive treatments during the initial 8 weeks of therapy. Serial CEA determinations demonstrated a parallel relationship with clinical progression in six of seven patients.

Dietary vitamin A and risk of cancer in the Western Electric study.

Intake of dietary provitamin A (carotene) was inversely related to the 19-year incidence of lung cancer in a prospective epidemiological study of 1954 middle-aged men. The relative risks of lung cancer in the first (lowest) to fourth quartiles of the distribution of carotene intake were respectively, 7.0, 5.5, 3.0, and 1.0 for all men in the study, and 8.1, 5.6, 3.9, and 1.0 for men who had smoked cigarettes for 30 or more years. Intake of preformed vitamin A (retinol) and intake of other nutrients were not significantly related to the risk of lung cancer. Neither carotene nor retinol intake was significantly related to the risk of other carcinomas grouped together, although for men in whom epidermoid carcinomas of the head and neck subsequently developed, carotene intake tended to be below average. These results support the hypothesis that dietary beta-carotene decreased the risk of lung cancer. However, cigarette smoking also increases the risk of serious diseases other than lung cancer, and there is no evidence that dietary carotenoids affect these other risks in any way.

Radiation carcinogenesis in man: new primary neoplasms in fields of prior therapeutic radiation.

Nine patients are presented in whom new malignant neoplasms developed in fields of prior irradiation. The prior irradiation had been administered to these patients for previously confirmed cancers, lesions suspected of being cancer (but never confirmed as such), and for non-neoplastic disorders. Each of these cases is relatively unique and several present the first association between prior radiation therapy and the subsequent neoplasm or neoplasms which developed.

Cytotoxic chemotherapy for cancer in Felty's syndrome: role of lithium carbonate.

A 61-yr-old white man with Felty's syndrome, who had previously undergone splenectomy, presented for cytotoxic chemotherapy. Random granulocyte counts remained low, prohibiting the initiation of such treatment. A trial of lithium carbonate was instituted, resulting in prompt elevation of granulocyte counts into the normal range. Cytotoxic chemotherapy was then administered, and fluctuations of neutrophil counts similar to those of hematologically normal individuals were observed.

High blood pressure and 17-year cancer mortality in the Western Electric Health Study.

A positive association between elevated blood pressure and risk of death from cancer has been observed in four long-term prospective studies. In the Western Electric Health Study, the relationship was specific to death from renal cell carcinomas and epidermoid cancers of the head and neck. The relationship with epidermoid head and neck cancer was indirect, resulting from the effects of alcohol consumption on both blood pressure and on risk of this cancer. The relationship with kidney cancer was probably due to effects of abnormal renal cell activity. The association between blood pressure and cancer mortality at other sites was not significant.

PIP: The authors examine the relationship between high blood pressure and cancer mortality. Data are from the Western Electric Health Study, which covered a sample of 3,107 Chicago men aged 40-55 who were followed for 17 years beginning in 1957. The relationships between high blood pressure and mortality from cancer in different sites are explored

5-Fluorouracil, methyl-CCNU, and radiotherapy with or without testolactone for localized adenocarcinoma of the exocrine pancreas: a Southwest Oncology Group Study.

Since August 1975, 69 patients with localized pancreatic carcinoma (extent of tumor confined to a 15 cm x 15 cm radiotherapy port) have received either Regimen A, comprising radiotherapy (6,000 rad) to the tumor area with simultaneous combination chemotherapy utilizing methyl-CCNU, 125 mg/m2 orally, every six weeks, and 5-fluorouracil, 400 mg/m2 intravenously, weekly; or Regimen B, comprising Regimen A with the addition of testolactone, 200 mg, orally every day. Thirty-eight patients on Regimen A and 30 patients on Regimen B are currently evaluable. Median survival, which appeared not to be affected by the addition of testolactone, was 38 weeks for those on Regimen A and 30 weeks for those on Regimen B (P = 0.677). The median survival time for all patients was 38 weeks. Good performance status did correlate with improved survival vs. poor performance status (46 weeks vs. 20 weeks, P = .008). Fifteen patients have survived for more than 52 weeks, with the longest survival time being 160 + weeks, and in 3 cases all therapy has been discontinued. However, most patients experienced moderate to severe hematologic toxic reactions. There was one treatment-related death and significant gastrointestinal bleeding developed in 6. Because of the toxic reactions of this program, it should not be considered in favor of similar less aggressive programs.