Cancer and aplastic anemia in British Columbia farmers.

For evaluation of occupational mortality in agriculture, age-standardized proportional mortality ratios (PMR) were calculated for 28,032 male farmers with the use of British Columbia (B.C.) death registrations collected from 1950 to 1978. Farmers had significantly elevated risks of death from cancer of the lip (PMR = 191, P = .05), stomach (PMR = 119, P less than .0001), and prostate gland (PMR = 113, P less than .001). In addition, leukemia was higher than expected (PMR = 122, P less than .01), as was aplastic anemia (PMR = 174, P less than .01). The elevated risks were fairly consistent over the 29-year period for stomach, prostate gland, and lip cancer, as well as for leukemia. The PMR for aplastic anemia was highest for the years 1950-59 and declined over the next 19 years. Farmers also showed significant mortality deficits for several important cancer sites, including esophagus (PMR = 59, P less than .0001), colon (PMR = 84, P less than .001), larynx (PMR = 62, P less than .01), and lung (PMR = 66, P less than .0001) for the period 1950-78. More detailed studies in B.C. will be necessary to confirm and extend these cancer-agriculture associations.

Differences in incidence rates of cancers of the respiratory tract by anatomic subsite and histologic type: an etiologic implication.

Data from nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results Program (1973-1982) were analyzed to determine whether the incidence of different histologic types of respiratory tract cancers varies by anatomic location. The variation in cancer incidence among respiratory tract subsites was remarkable for squamous cell carcinoma, but the variation was less prominent for adenocarcinoma. The rates of squamous cell carcinoma and adenocarcinoma along the airways correspond closely with the deposition pattern of large and small smoke particles, respectively. Also, the rates of adenocarcinoma parallel the distribution of surface glandular cells of the respiratory tract. Our results support the hypothesis that anatomy and physiology, in conjunction with size of particles in inhaled cigarette smoke, play an important role in the genesis of specific histologic types of respiratory tract cancers.

Treatment of recurrent and metastatic head and neck cancer with cisplatin/etoposide/bleomycin.

Cisplatin/etoposide/bleomycin (DEB) was given as an outpatient regimen in a novel weekly schedule to 27 patients with recurrent and/or widely metastatic cancer of the head and neck region. Six of these patients also received mitomycin (DEB/M) when their disease failed to respond after at least three weekly DEB doses. All but three patients had been treated previously with radiotherapy directed to the primary site and regional nodal disease; four had also received chemotherapy with cisplatin or carboplatin. Before treatment with DEB, 19 patients had distant metastases. Of an intended 12 doses per patient, a mean of 8.2 was achieved. Myelosuppression was the major toxicity, with neutropenia in 45% of patients and significant anemia in 26%. The overall response rate to DEB in 27 patients was 59%, increasing to 70% after the addition of mitomycin. There were two complete and 17 partial responses. The median duration of response was 12 weeks and median survival was 6 months, with 20% of patients surviving 1 year. We conclude that the relatively short survival time together with the significant toxicity of the DEB/M regimen does not warrant its routine use in clinical practice. However, this regimen, or one patterned on it, should be evaluated in combination with radiotherapy as the initial treatment for selected patients with previously untreated head and neck cancer.

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine.

The authors compared, in a double-blind, randomized, crossover study in 13 healthy adult volunteers, the single- and multiple-dose pharmacokinetics, relative bioavailability, and side effects of a new oral sustained-release formulation of codeine (SRC) containing 150 mg codeine base, with oral immediate-release codeine phosphate (IRC). Sustained-release codeine was given at a dose of 150 mg every 12 hours for 5 doses; IRC was given at a dose of 60 mg (2 x 30 mg) every 4 hours for the first 3 doses, and 30 mg every 4 hours thereafter for 12 doses. Plasma codeine levels were determined using a sensitive and specific high-performance liquid chromatography method and corrected for dose administered and codeine base equivalent. Mean values for single-dose pharmacokinetic parameters for SRC and IRC, respectively, were: Cmax of 217.8 and 138.8 ng/mL; Tmax of 2.3 and 1.1 hours; AUC0-inf of 1202.3 and 1262.4 ng.mL-1.hour-1; and t1/2el of 2.6 hours for both formulations. Their respective mean steady-state pharmacokinetic parameters were: Cmax of 263.8 and 222.9 ng/mL; Tmax of 3.2 and 1.1 hours; AUC0-12h of 1576.4 and 1379.1 ng.mL-1.hour-1; and t1/2el of 2.8 and 2.3 hours. These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels. The sustained-release character of SRC can be explained by a delayed absorption, which is not limiting to drug elimination. Sustained-release codeine provides higher plasma codeine levels over a broader time interval and is expected to improve pain management.

The role of chemotherapy in the treatment of breast cancer.

A wide variety of approaches are being applied to the therapy of breast cancer. Treatment begins with a biopsy followed by mastectomy to remove the primary tumor. The risk category must be determined and, at present, an axillary dissection appears to be required; in the future, tumor cell markers may replace the role of an axillary dissection in the determination of risk category (TORMEY et al., 1975). If the nodes are positive, adjuvant chemotherapy and possibly immunotherapy should be considered. A positive estrogen receptor assay suggests that patients may also benefit from endocrine treatments. If it is negative, the chances of responding to hormonotherapy are very limited, except, perhaps, for anti-estrogens (McGUIRE, et al., 1975). Adjuvant therapy for patients with negative nodes is not recommended at this time; this view may have to be modified as the results of current adjuvant studies become available. We have at hand the means to improve the cure rate of patients with breast cancer. We are getting better diagnostic methods and find more patients with negative nodes. We know more about the primary treatment and have systemic modalities that are effective in the adjuvant situation. The immediate problem is to learn how to put these treatments together, and this task has been undertaken by on-going clinical trials. We are anticipating the results with optimism.

Identification of occupational cancer risks using a population-based cancer registry.

The study of Xuan Wei fuel use and lung cancer mortality and also the interim case-control study suggested an association between domestic smoky coal use and Xuan Wei lung cancer. The collaborative studies of physical characterization, chemical analysis, and toxicology further substantiated this linkage. The Xuan Wei residents who used smoky coal inhaled extremely high concentrations of mostly submicron-sized particles, which can be inhaled and deposited effectively deep in the lung. These fine particles were composed mostly of organic compounds (72%), including mutagenic and carcinogenic organic compounds, especially in the aromatic and polar fractions. These residents were exposed to polycyclic aromatic compounds, such as benzo[a]pyrene, at comparable or higher levels than those measured in coke oven plants and other occupational environments (International Agency for Research on Cancer 1984). In comparison with wood and smokeless coal combustion emissions, the organic extracts of smoky coal emission particles showed much higher activity of genotoxicity and carcinogenicity. These results all point to a strong etiological link between the complex organic mixtures from smoky coal emissions and Xuan Wei lung cancer. This study and studies reported by other investigators (de Koning et al. 1984) suggested little association between indoor open-fire wood smoke and lung cancer. The less efficient lung deposition of the larger particles from wood combustion, as well as the lower concentrations of biologically active organic compounds, may contribute to the low rate of lung cancer in the wood-burning communes. As to the smokeless coal emissions, the lower particulate concentration and the lower organic content of the particles emitted may also contribute to the low lung cancer rate in the commune using this fuel. In conclusion, the complex organic mixtures from combustion emissions are genotoxic and carcinogenic in animal and in vitro assays. The magnitude of the cancer risks from the complex organic mixtures in man depends on the degree of the exposure, the types of the compounds contained in the mixtures, and the concentrations of these biologically active compounds present in the combustion emissions.

The evaluation of analgesic effects in cancer patients as exemplified by a double-blind, crossover study of immediate-release versus controlled-release morphine.

We compared the effects of controlled-release and immediate-release morphine preparations in adult patients with moderate-to-severe cancer pain and report methodologic approaches to pain evaluation. The study consisted of a two-phase randomized crossover trial preceded by a titration phase; all phases were conducted under double-blind conditions. To evaluate pain intensity, a visual analogue scale (VAS) and the Present Pain Intensity scale of the McGill Pain Questionnaire were used. Additional morphine solution for breakthrough pain was used as an outcome measure. Pain was evaluated nine times daily, which permitted correlation of pain scores with the pharmacokinetic patterns of the test drugs. Side effects were rated once daily, using a scale from 0 to 3. To assess the relative importance of side effects, a toxicity index was designed based on both the intensity and duration of each side effect. The overall VAS pain scores during treatment with controlled-release and immediate-release morphine were 1.3 (SD = 0.1) and 1.4 (SD = 0.2), respectively. Use of supplemental morphine solution for breakthrough pain expressed as the percentage of the daily dose of the test drug was 5.5% for the controlled-release drug and 10.9% for the immediate-release drug. Differences in pain scores, side effects, and supplemental morphine requirement between the two groups were not significant. We discuss methodologic issues in double-blind clinical trials of analgesics, in particular the validity of "Patient Preference" as an outcome measure and problems related to the titration phase.

Identification of occupational cancer risks in British Columbia. A population-based case-control study of 995 incident breast cancer cases by menopausal status, controlling for confounding factors.

Lifetime occupational histories as well as information on known and suspected breast cancer risk factors were collected by means of a self-administered questionnaire from 1018 women with incident breast cancer ascertained from the British Columbia Cancer Registry, and from 1020 population controls. A matched case-control study design was used. Conditional logistic regression for matched sets data and the likelihood ratio were used in a two-step procedure and were performed separately for pre-menopausal women, post-menopausal women, and for all cases combined. Excess risk was noted for several white-collar occupations. Significantly increased risk was observed: (1) among pre-menopausal women: in electronic data-processing operators; barbers and hairdressers; in sales and material processing occupations; and in the food, clothing, chemical and transportation industries; (2) among post-menopausal women: in schoolteaching; in medicine, health, and nursing occupations; in laundry and dry-cleaning occupations; and in the aircraft and automotive, including gasoline service station, industries. Several significant associations were also seen in the combined group of pre- and post-menopausal women, particularly in crop farmers and in the fruit and vegetable, publishing and printing, and motor vehicle repair industries. The results of this study suggest excess breast cancer risk in a number of occupations and industries, notably those that entail exposure to solvents and pesticides.

Identification of occupational cancer risks in British Columbia. Part II: A population-based case-control study of 1516 Prostatic cancer cases.

We have, as part of a program aimed at detecting occupational risk factors in British Columbia, collected lifetime occupational histories from 15,643 incident cancer cases, of whom 1519 had a diagnosis of prostate cancer. Occupational risks for this cancer site are examined using this large data set, and the results are presented in this report.