Biological and Clinical Results of a Neuroimmunotherapy with Interleukin-2 and the Pineal Hormone Melatonin as a First Line Treatment in Advanced Non-small Cell Lung Cancer

The metastatic non-small cell lung cancer (NSCLC) still remains an untreatable disease, and the role played by chemotherapy has yet to be defined. The new immunotherapeutic strategies, such as interferon and IL-2, seem to be also less effective, since they generally determine only a stabilisation of disease. On the basis of previous experimental results suggesting a synergistic action between IL-2 and the pineal neurohor-mone melatonin (MLT), a study was started to evaluate the clinical efficacy and toxicity of a neuroimmuno-therapeutic combination consisting of IL-2 plus MLT as a first line therapy in metastatic NSCLC. The study included 20 patients (adenocarcinoma: 10; epidermoid cell carcinoma: 7; large, cell carcinoma: 3). MLT was given orally at a dose of 10 mg day-' at 8.00 pm every day, starting 7 days before the onset of IL-2 administration. IL-2 was given subcutaneously at a dose of 3 x 106 IU m-2 every 12 h for 5 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In responder patients or in those with stable disease, a second cycle was given after a rest-period of 21 days. A partial response was achieved in 4/20 (20%) patients. Ten other patients had a stable disease (50%), whereas the last six patients progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapeutic therapy with IL-2 and the pineal hormone MLT may represent a new effective and well tolerated treatment in metastatic NSCLC, with results comparable to those obtained with chemotherapy, but with an apparent lower biological toxicity. In the last 50 years, no medical therapy has substantially improved the prognosis of non-small cell lung cancer (NSCLC) (Hansen, 1987). The prognosis of metastatic NSCLC still remains poor, with median survival generally not greater than 20 weeks. Chemotherapy has a limited impact, and does not determine any evident benefit on the survival time. Therefore, these poor results justify the investigation of new medical strategies in the treatment of metas-tatic NSCLC, such as immunotherapy and hormonotherapy. Because of its fundamental role in the activation of an effective host antitumour immune response, interleukin-2 (IL-2) represents one of the most promising cytokines in the immune control of cancer growth (Grimm et al., 1982). At present, very few results are available about the activity of IL-2 in NSCLC (Rosenberg et al., 1987; Ardizzoni et al., 1990; Krigel et al., 1991). Preliminary data would suggest that IL-2, despite its biological efficacy in …

President Clinton's creation of a broadbased presidential council on sustainable development has been heralded as an opportunity for the administration to forge alliances between those concerned mainly with economic growth and those concerned with environmental protection. Clinton's council has been contrasted to former Vice President Quayle's Council on Competitiveness, which took a probusiness stance on the environment.
Industry sources welcomed the June 14 announcement as a sign of the administration's committment to involving business interests in environmental decision-making. Some environmental sources worried, however, that unlike Quayle's Council on Competitiveness, this new council would lack influence in the development of administrative policy. Others respond that this skepticism is unwarranted for several reasons. First, Clinton's announcement came two weeks after a national conference on sustainable development which recommended the establishment of such a council, at which Vice President Gore strongly advocated strategies for sustainable development. Second, the stature of many of the members of the 25-member council virtually guarantee the council will receive the president's attention on environmental policy decisions. Chavis. In addition to the five cabinet members, the council is made up of eight representatives of industry, two of minorities, six of environmental groups, one from labor, one state representative, and one philanthropist.

Members
The council will be chaired by David Buzzelli, vice president and corporate director of Environment, Health, Safety, and Public Affairs at Dow Chemical Company, and Jonathon Lash, president of the World Resources Institute. According to Lash and Buzzelli, the council's top priorities will include global climate change and global standards for worker safety and health. A plan of action by the council, noted Buzzelli, may be to "stand back from issues of the day and take a broad perspective." The council will meet four times a year for a two-year period. Advancing Women's Health "Why do women have poorer health outcomes?" asked Susan Blumenthal, scientific director of the Society for the Advancement of Women's Health Research at the society's 1993 scientific advisory meeting on the environment. "It may be derived from adverse impacts of environmental factors such as toxins in the atmosphere, drug exposures, or substances of abuse." The meeting brought together leaders from medical and professional societies, academia, and government such as the American College of Occupational and Environmental Medicine, Columbia University School of Public Health, the University of Texas/M.D. Anderson Cancer Center, EPA, and NIEHS. Consumer advocate Ralph Nader and Congressman Henry Waxman (D-California), chair of the House Subcommittee on Health and the Environment, delivered special addresses.
Participants at the meeting focused on setting a research agenda to ascertain links between health and environmental and social stressors. Discussion called for more basic research at the biochemical, cellular, and molecular levels in the context of physiological events. Menstruation, pregnancy, childbirth, and menopause may influence the prediction of risks and outcomes.
"Disease is really the outcome of three factors-environment, both internal and external, hormones, and microscopic elements in the cell," said John MacLachlan, scientific director of NIEHS, which cosponsored the meeting. "In the case of breast, cervical, and ovarian cancer, osteoporosis, endometriosis, fibroids, and sexually transmitted diseases, we're . . still at the point where understanding the envi-ronment's role on any of these disorders is a top priority and strategy from a research standpoint," MacLachlan said. "Diseases and dysfunctions associated with estrogens that occur later in life raise the question of earlier exposures." Ellen Silbergeld of the Environmental Defense Fund agreed. Silbergeld said that bone is a major repository for lead that could resurface because of changes in bone physiology and hormonal regulation of mineral metabolism, particularly during menopause. "How our body handles lead is very complex," she said. "Ninety percent is absorbed into our bones." The question according to Silbergeld is what is the impact, given that lead "may be recirculated back into the body with potential toxic consequences.
Research recommendations from the meeting include educating public health officials and physicians on precise human exposure assessment; setting standard tracking techniques for pollutant exposures; establishing registries and databases for breast implants and key epidemiological reporting with complete health profiles; weighing the variable effects of fat and diet over a woman's lifetime; devising new ways to measure clinical sensitivity; and accessing findings of corporations, pharmaceutical companies, and medical specialty societies.
Interagency monitoring of contaminant-induced illness was encouraged. Participants also urged subprograms within the NIH Women's Health Initiative to study the effects of environmental toxins on cancer, osteoporosis, and endometriosis.