Preliminary report on reduction of esophagitis by amifostine in patients with non-small-cell lung cancer treated with chemoradiotherapy.

Esophagitis is a major toxicity of chemoradiotherapy for lung cancer. Twenty-four patients with non-small-cell lung cancer received induction chemotherapy (paclitaxel/carboplatin) followed by concurrent thoracic irradiation (RT) and weekly paclitaxel. Acute esophagitis was scored weekly. Since a high rate of grade 3 esophagitis was noted in the initial group of 12 patients, amifostine (AMI) 500 mg intravenously twice weekly was added to the regimen in the subsequent 12 patients. Esophagitis Index (EI) was calculated as an area under the curve reflecting esophagitis grade over time. Median number of AMI doses was 12 per patient. AMI was well tolerated. Two patients were not evaluable for esophagitis. The incidence of grade 3 esophagitis was 18% in the initial 11 patients versus 9% in the AMI-treated patients (P = not significant). Mean EI was numerically lower in the AMI-treated patients than in the initial group (5.1 vs. 11.6, P = 0.14). The product of RT dose and length of esophagus in the RT field was larger in the AMI group (934 vs. 761, P = 0.035). Median survival time for all patients was 12.4 months. Esophagitis Index, a novel measure of the severity and duration of acute esophagitis, may be reduced in lung cancer patients receiving twice-weekly AMI with thoracic RT and paclitaxel. Twice weekly AMI did not eliminate grade 3 esophagitis; therefore, dose escalation of AMI is planned. The effect of AMI was not due to the shorter irradiated esophageal length. A phase III randomized trial is now open to assess AMI's effect on esophagitis.

Antiemetic therapy.

With the increasing prevalence of chemotherapy in the treatment of neoplasia, antiemetic therapies have become essential and sophisticated: phenothiazines, benzodiazepines, steroids, substituted benzamides, butryphenones, anticholinergics and antihistamines, cannabinoids, and the 5-HT 3 receptor antagonist are reviewed.

Elective introduction to oncology.

Since 1974, the St. George Medical Society, a component of the American Cancer Society's Philadelphia Division's Professional Education Program, has sponsored paid summer clinical and research fellowships for Philadelphia medical students completing their first year. Six lectures at the student level are presented throughout the year. Students run a single society, elect officers, and select site and speakers under the guidance of the St. George Medical Society Subcommittee. Faculty from six medical schools and individual faculty preceptors donate time to provide a one-on-one summer experience in medical oncology, surgical oncology, gynecologic oncology, radiation oncology, pathology, and cancer-related research in university hospitals, community hospitals, and private offices. Financial support is provided by directed donations. Currently 50 clinical fellowships are offered. Since its inception, over 750 "fellowships" have been awarded, and over 3,000 students have attended the lectures. The program successfully provides a voluntary one-on-one introduction to clinical oncology in a reproducible format.

Clinical results and immunologic effects of a mixed bacterial vaccine in cancer patients.

A biological response modifier, mixed bacterial vaccine (MBV), derived from Streptococcus pyogenes and Serratia marcescens was used as a single agent in the treatment of 11 patients with refractory malignancies. MBV's effect on interleukin-2 (IL-2) production, plasma interferon (IFN) and tumor necrosis factor (TNF) levels was monitored. Most patients' peripheral blood mononuclear cells continued to produce baseline to elevated levels of IL-2, in spite of age and disease status. Several patients maintained moderate to high IFN levels. In general there was little correlation between IL-2 and IFN levels or with the response to therapy. One of 11 patients had minor response, 1 of 11 had partial response, 4 of 11 had temporary stabilization of disease, and 5 of 11 had progressive disease. A patient with AIDS and Kaposi's sarcoma experienced a dramatic improvement in performance status and disease stabilization. In all patients side effects occurred only following i.v. and not i.m. administration and included fever and chills. No adverse hepatic, renal or hematologic effects were observed. MBV is a well-tolerated biological response modifier with modest activity in advanced human tumors.

The effect of a bacterial vaccine on tumors and the immune response of ICR/Ha mice.

This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37. The study examined MBV's biological properties and analyzed its chemical composition. The chemical composition varied with the growth media. A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three. MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV. MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity. MBV also had a striking effect on the immune response of mice to sheep red blood cells. When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold. Serum antibody levels also increased two- to threefold. MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response. However, the in vivo administration of MBV increased the in vitro response to MBV and the B-cell mitogen lipopolysaccharide. MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels.

Effect of the mixed bacterial vaccine on the immune response of patients with non-small cell lung cancer and refractory malignancies.

Since 1984, 13 patients were entered into our study and 12 patients have completed one or more cycles of treatment with mixed bacterial vaccine (MBV), a natural biologic response modifier derived from Streptococcus pyogenes and Serratia marcescens. Eight patients with refractory malignancy were treated with MBV only (0.1 ml intravenously [IV]) twice weekly for 3-16 weeks (colorectal cancer, pancreatic cancer, chronic lymphatic leukemia, hepatoma [two patients], sarcoma [three patients]). Four patients with advanced non-small cell lung cancer were treated with MBV in combination with low-dose cyclophosphamide, day 1; cisplatin, day 15; and MBV, 0.1 ml IV, days 5, 7, and 9. Two patients in this study received cyclophosphamide and cisplatin alone. The cycle was repeated every 28 days. Plasma interferon levels, interleukin-2 production by peripheral lymphocytes, and lymphocyte subpopulations were monitored. Interferon levels and interleukin-2 production showed increased or sustained values in general. In some patients, B-cells and helper T-cell populations increased, whereas T-suppressor cell numbers declined. With one exception, side effects were mild and consisted of fever greater than 37.8 degrees C (nine of 13), chills (11 of 13), increased respiratory rate (nine of 13), minor changes in blood pressure (seven of 13), and nausea (three of 13). One patient with non-small cell lung cancer had a partial response. Two patients with non-small cell lung cancer and one patient with refractory malignancy had stable disease and performance status at the end of 8 weeks of treatment; one patient with refractory malignancy was stable at the end of 4 weeks of treatment. In this pilot study, cancer patients treated with MBV showed objective evidence of immune stimulation with acceptable toxicity.