Arthur H. Rossof

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.

Preliminary clinical experience with cis-diamminedichloroplatinum (II) (NSC 119875, CACP)

Thirty‐one patients with metastatic cancer were treated with cis‐diamminedichloroplatinum (II), CACP, in dosages ranging from 7.5 to 200 mg/m2 BSA per course. Twenty‐two patients received more than one course. Toxicity to the initial course of CACP, up to 90 mg/m2 BSA, was minimal and transient in most patients. At higher dosage levels or following repeat courses, the drug‐related toxicity was more severe. Drug‐related toxicity was more severe in patients with abnormal excretory tracts. The most common and earliest side effects were nausea and vomiting. Hyperuricemia commonly occurred shortly after administration of CACP. A dosage‐dependent, generally transient, nephrotoxicity was noted within the first 10 days after a course of CACP. Moderate leukopenia and thrombocytopenia, as well as a progressive normocytic anemia with marrow erythroid hypoplasia, were observed as late as 3 to 4 weeks after injection of this agent. Audiologic impairment above the frequency range of normal speech was detected by audiometry. Objective tumor regression was seen in five patients, four of whom experienced moderate‐to‐severe toxicity.

Cytotoxicity and influence on radiation dose response curve of cis-diamminedichloroplatinum II (cis-DDP)

Abstract Exponentially growing Chinese hamster ovary (CHO) cells were exposed to varying doses of Cis-diamminedichloroplatinum II ( cis DDP) for I hour. Cytotoxicity was found to be dose dependent and the dose response curve has shoulder and exponential portions. D o on the exponential portion of the curve was found to be 2.8 μ/ml. The values of D q and the extrapolation number (n) corrected for single cells were found to be 3.1 μ/ml and 12.0 respectively. The influence of exposure to cis DDP on the radiation dose response curve was also studied. The radiation dose response curve of the CHO cells not exposed to cis DDP is characterized by a D o of 139 rad. The values of D q and n corrected for single cells are 105 rad and 4.5 respectively. Exposure to 8 /ml of cis DDP for 1 hour decreased D o to 102 rad when exposure was immediately prior to irradiation and to 106 rad when the exposure was immediately after irradiation. D q and n were found to be 140 rad and 18 for pre-radiation exposure and 137 rad and 15 for post-radiation exposure. This influence on the radiation dose response curve was not found to be cis DDP dose dependent since at higher concentration of cis DDP (10 μ/ml, 12 μ/ml, 16 μ/ml) D o , D p and n were found to be the same as at 8 μ/ml.

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.

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 betacarotene <5,000 (N=929) or <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. (Epidemiology 1992;3:282–287)

Mitomycin C, methyl-CCNU and 5-fluorouracil in the treatment of metastatic colorectal carcinoma

SummaryThe combination of mitomycin C, methyl-CCNU and 5-fluorouracil produced no objective tumor regressions in 25 evaluable patients with metastatic colorectal carcinoma. Patients who achieved stable disease survived significantly longer than patients who had progressive disease. This difference appeared to be more probably related to pre-treatment characteristics of the patients than caused by treatment. Serial CEA determinations revealed a parallel relationship with tumor behavior in 17 of 19 patients.

Phase II trial of 4′ deoxydoxorubicin (DXDX) for unresectable non-small cell bronchogenic carcinoma

SummaryA 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.

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

SummaryFifteen 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.

Two cases of pancreatic carcinoma.

AbstractThree cases of pancreatic carcinoma possibly induced by cancer treatment have been previously documented. These include one case following radiation for lymphoma (1), one case following chemotherapy for leukemia (2), and one case after both radiation and chemotherapy for lymphoma (3). We report two additional cases of pancreatic carcinoma following radiation and chemotherapy for lymphoma.