We describe here the preliminary results of the systemic administration of autologous lymphokine-activated killer (LAK) cells and the recombinant-derived lymphokine interleukin-2 to patients with advanced cancer. This regimen was based on animal models in which the systemic administration of LAK cells plus interleukin-2 mediated the regression of established pulmonary and hepatic metastases from a variety of murine tumors in several strains of mice. We treated 25 patients with metastatic cancer in whom standard therapy had failed. Patients received both 1.8 to 18.4 X 10(10) autologous LAK cells, generated from lymphocytes obtained through multiple leukaphereses, and up to 90 doses of interleukin-2. Objective regression of cancer (more than 50 per cent of volume) was observed in 11 of the 25 patients: complete tumor regression occurred in one patient with metastatic melanoma and has been sustained for up to 10 months after therapy, and partial responses occurred in nine patients with pulmonary or hepatic metastases from melanoma, colon cancer, or renal-cell cancer and in one patient with a primary unresectable lung adenocarcinoma. Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Further development of this approach and additional patient follow-up are required before conclusions about its therapeutic value can be drawn.
Inflammatory myofibroblastic tumors may be a locally aggressive and destructive neoplasm. Tumor recurrence is unusual following complete surgical resection or organ-preserving combined modality therapy.
Interleukin-2 (IL-2) is a 15,000 dalton glycoprotein produced naturally by human T-cells during an immune response. IL-2 has been demonstrated to have substantial activity alone or in combination with the adoptive transfer of lymphokine-activated killer cells in murine tumor models. IL-2 derived from both natural (Jurkat human T-cell tumor) and recombinant (Escherichia coli) sources has been studied in Phase I protocols designed to evaluate toxicity in patients with a variety of solid tumors and to ascertain improvement in clinical parameters and immunologic status. A total of 16 patients (7 with acquired immune deficiency syndrome [AIDS] and 9 with non-AIDS malignancies) were treated with Jurkat derived IL-2. The total maximum dose (1.3 X 10(5) U/kg) was limited only by supply of this reagent. A total of 25 patients have been treated with recombinant IL-2 (RIL-2) alone. Dose-limiting toxicity manifested by marked malaise and weight gain was achieved with doses of RIL-2 of 10(6) U/kg as a single bolus or 3000 U/kg/hr. IL-2 could be administered intraperitoneally with similar toxicity. Minimal renal or hepatic toxicity was demonstrated. Hematologic toxicity was limited to mild anemia (25/25), thrombocytopenia (10/25), and marked reversible eosinophilia (15/25). Pronounced weight gain greater than 2 kg (16/25) occurred in most patients, primarily those who received cumulative doses of greater than 1-3 X 10(5) U/kg of IL-2. The weight gain amounted to as much as 10% to 20% of the pretreatment weight over 3 weeks of treatment and limited our ability to give higher doses. Two partial responses (greater than 50% decrease in cross sectional diameters) were seen in two patients with melanoma metastatic to the lung.
Although adrenal metastases are frequently noted with non-small-cell lung cancer (NSCLC) at autopsy, their incidence in patients with operable NSCLC is unclear. We prospectively assessed consecutive patients with otherwise operable NSCLC for the incidence and histology of unilateral adrenal masses. Assessment included blood chemistries, lung function tests, bronchoscopy, chest x-ray, bone scan, and computed tomography (CT) of the head, chest, and upper abdomen. Of 246 patients with otherwise operable NSCLC, 10 (4.1%) had a unilateral adrenal mass. Unilateral adrenal masses were needle-aspirated under CT control. If cytology was nondiagnostic, adrenalectomy was performed. Four (40%) of 10 patients had adrenal metastases proven by needle aspiration. Of the six (60%) patients with benign unilateral adrenal masses, one was demonstrated by needle aspiration. In the other five patients, a nondiagnostic needle aspiration led to adrenalectomy, which yielded two adenomas, two hyperplastic nodules, and one hemorrhagic cyst. There was no significant difference between the patients with benign and metastatic unilateral adrenal masses with respect to patient age or stage and size of adrenal mass. Patients with benign unilateral adrenal masses underwent curative resection of their NSCLC and had significantly prolonged survival compared with patients with metastatic unilateral adrenal masses treated with chemotherapy (P = .037). Median survival of patients with benign and metastatic unilateral adrenal masses was greater than 30 months and 9 months, respectively. In conclusion, the presence of unilateral adrenal masses in patients with otherwise operable NSCLC should not preclude thoracotomy without pathologic proof of metastatic disease.
A safely tolerated dose of daily subcutaneous IL-6 is 10 micrograms/kg, with hepatotoxicity and cardiac arrhythmia being the dose-limiting toxicities at 30 micrograms/kg. Phase II trials of IL-6 administered subcutaneously daily for at least 7 days for two cycles with an intervening week of rest are recommended for phase II trials. However, patients with extensive replacement of liver by tumor and abnormal liver functions should receive IL-6 therapy with caution.
Low-dose intravenous bolus IL-2 represents an effective regimen for the treatment of metastatic RCC, with preliminary results comparable to those observed with high-dose IL-2. Low-dose IL-2 can be administered with significantly fewer complications, reduced use of vasopressor support, and fewer admissions to an intensive care unit (ICU).
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