Showing papers by "Joan H. Schiller published in 1993"

Paraneoplastic syndromes associated with lung cancer

Abstract: Paraneoplastic syndromes are caused by systemic factors that are produced at a site distant from the primary tumor or its metastases. Although these syndromes can be observed in a variety of tumor types, they are commonly found in lung cancer, particularly small cell lung cancer. In this review, we focus on recent advances in the diagnosis and treatment of two of the more well-documented paraneoplastic syndromes--endocrinologic and neurologic systemic manifestations of cancer.

Effects of cytokines on the pituitary-adrenal axis in cancer patients.

Abstract: Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cyto...

A Direct Comparison of Immunological and Clinical Effects of Interleukin 2 with and without Interferon-α in Humans

Abstract: Interleukin 2 (IL-2) and interferon-α (IFN-α) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-α in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-α and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-α and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 × 106 units/m2/day or 3.0 × 106 units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-α (0.5 × 106 or 5 × 106 units/m2/day) was administered s.c. on days 1–4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-α for course 2, or IL-2/IFN-α in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-α. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-α. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-α group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum β2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL-2 alone and IL-2 plus IFN-α. No dose response effect for IFN-α was observed for any of the parameters assessed. Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-α and IL-2. Two patients had a partial response, and 5 patients had a minor response (partial plus minor response rate, 18%). In conclusion, we did not observe a difference in biological activity between IL-2 and IL-2 plus IFN-α in any of the immunological parameters we studied. Although this regimen was relatively well-tolerated, we cannot conclude that IFN-α adds significantly to the immunological or therapeutic activity of IL-2 alone.

Activation of multiple effector mechanisms to enhance tumor immunotherapy.

Abstract: Recent technical advances have enabled the generation of clinical reagents for immunotherapy. Currently, treatment protocols combining both interleukin-2 (IL-2) and tumor-specific monoclonal antibody are underway at the University of Wisconsin Comprehensive Cancer Center and elsewhere. These approaches are based on the hypothesis that IL-2-activated lymphocytes will use tumor-reactive antibody to more selectively and effectively destroy tumor in vivo. Just as IL-2 can activate lymphocytes to destroy antibody-coated tumor cells, other agents can activate neutrophils and monocytes to destroy antibody-treated tumor cells. We are investigating, in laboratory and clinic, approaches aimed at eventually using combinations of distinct antibody-based tumor recognition mechanisms in patients whose monocytes, neutrophils, and lymphocytes have been simultaneously activated with multiple biologic agents.

A pilot phase II trial of continuous-infusion interleukin-2 followed by lymphokine-activated killer cell therapy and bolus-infusion interleukin-2 in renal cancer

Abstract: Nine patients with metastatic renal cell carcinoma were entered into a pilot protocol including a 4-week regimen utilizing human recombinant interleukin-2 (IL-2) and in vitro lymphokine-activated killer (LAK) cells. The regimen included 2 weeks (4 days of treatment and 3 days of rest/week) of continuous-infusion (c.i.) IL-2 at 3 x 10(6) U/m2/day, followed by two leukaphereses. LAK cells were cultured in vitro for 48 to 72 h and administered as a single infusion, followed by 9 days of bolus i.v. injections of 10(6) U IL-2/m2/dose, given every 8 hours (t.i.d.). The average (+/- SD) number of LAK cells infused per patient was 7.2 x 10(10) (+/- 3.5 x 10(10)). One patient showed > 50% shrinkage of tumor (lung + renal bed recurrence). Toxicity was similar to that encountered in other studies using similar IL-2 doses and LAK cells and consisted of fever, hypotension, fluid retention, and reversible renal insufficiency. These results indicate that the 2 weeks of IL-2 c.i. provided conditions enabling the harvest of large quantities of mononuclear cells from the peripheral blood of patients; this could be useful for future trials requiring the use of in vitro activated lymphocytes. Nevertheless, these pilot data suggest that this regimen of prolonged t.i.d. IL-2 administration after the LAK infusion does not seem to generate any improvement in antitumor effects from those obtained using other LAK + IL-2 regimens.

Phase I trial of mitoxantrone and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced solid malignancies

Abstract: Purpose To determine the maximally tolerated dose (MTD) and pharmacokinetics of high-dose mitoxantrone and document the toxicities and side effects of mitoxantrone when administered with GM-CSF.

A comparison of knowledge and communication skill evaluations by written essay and oral examinations in preclinical medical students.

Abstract: While both oral and written communication skills are important in the daily work of physicians, medical school evaluation methods focus on content of written essays or often answers to multiple choice questions. To determine the feasibility and value of oral examinations for preclinical medical students, we gave a written short essay examination and an oral examination on the same question to 106 second‐year medical students in a required neoplastic diseases course. Examination performance by each method was evaluated according to the same specific content and, separately, based on four communication skills criteria. We found high levels of inter‐rater reliability with two oral examiners for both content and skills. Content and skills performance on both written and oral evaluations could be separately determined. Content performance was greater on the written evaluation.