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Titolo:
BIOLOGIC AND CLINICAL EFFECTS OF CONTINUOUS-INFUSION INTERLEUKIN-2 INPATIENTS WITH NONSMALL CELL LUNG-CANCER
Autore:
ARDIZZONI A; BONAVIA M; VIALE M; BALDINI E; MEREU C; VERNA A; FERRINI S; CINQUEGRANA A; MOLINARI S; MARIANI GL; ROEST GJ; SHARENBERG J; PALMER PA; ROSSO R; ROPOLO F; RASO C;
Indirizzi:
IST NAZL RIC CANC,DEPT MED ONCOL,VIALE BENEDETTO XV,10 I-16132 GENOA ITALY IST NAZL RIC CANC,DEPT BRONCHOL I-16132 GENOA ITALY IST NAZL RIC CANC,PHARMACOL LABS I-16132 GENOA ITALY IST NAZL RIC CANC,PHARMACOTOXICOL LABS I-16132 GENOA ITALY OSPED SAN MARTINO GENOVA,DEPT PNEUMOL GENOA ITALY OSPED SAN MARTINO GENOVA,DEPT CARDIOL GENOA ITALY FREE UNIV AMSTERDAM HOSP,DEPT PATHOL AMSTERDAM NETHERLANDS EUROCETUS BV AMSTERDAM NETHERLANDS
Titolo Testata:
Cancer
fascicolo: 5, volume: 73, anno: 1994,
pagine: 1353 - 1360
SICI:
0008-543X(1994)73:5<1353:BACEOC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-INFILTRATING LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; DOSE INTERLEUKIN-2;
Keywords:
INTERLEUKIN-2; IMMUNOTHERAPY; NONSMALL CELL LUNG CANCER; PULMONARY FUNCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
15
Recensione:
Indirizzi per estratti:
Citazione:
A. Ardizzoni et al., "BIOLOGIC AND CLINICAL EFFECTS OF CONTINUOUS-INFUSION INTERLEUKIN-2 INPATIENTS WITH NONSMALL CELL LUNG-CANCER", Cancer, 73(5), 1994, pp. 1353-1360

Abstract

Background. Interleukin-2 (IL-2) has shown antitumor activity in someneoplasms, such as melanoma and renal carcinoma, but toxicity derivedfrom bolus administration is significant, particularly at the cardiorespiratory level. Methods. To test feasibility, antitumor activity, pulmonary and systemic immunologic effects, and pulmonary function changes of continuous-infusion recombinant IL-2 given to patients with non-small cell lung cancer, eleven subjects with Stage III-IV disease weretreated in a standard pulmonary medicine unit with a dose of 18 million IU/m(2)/day from day 1 to day 13 with 1-day rest on day 7. A secondinduction course was given after a 3-week rest. In patients with nonprogressive disease, four maintenance courses of 6 days' duration at the same dose were planned. Immunologic tests, including lymphocyte phenotype analysis and assays for the detection of tumor necrosis factor (TNF) and of anti-IL-2 antibodies, were performed before and after treatment in serum and bronchoalveolar lavage fluid (BAL). Cardiopulmonaryfunction tests, including spirometry, arterial blood gas analysis, diffusion capacity, and echocardiography, were obtained before, during, and after treatment. Results. Twenty-one cycles (15 induction courses plus 6 maintenance courses) were administered. No patient was able to complete the six planned courses, and only 3 patients entered the maintenance phase. Reasons for discontinuation included progressive disease in five cases, toxicity in three cases, and patient request in threecases. The most common side effects were fever, hypotension, oliguria, and elevated serum creatinine and liver enzyme levels. No patient required intubation or intensive care. No objective response was seen, and the median survival time was 10 months. Lymphocytosis and eosinophilia were observed in all patients. Surface marker analysis revealed a statistically significant increase in the percentage of CD3+, CD4+, CD25+ and DR+ cells in peripheral blood. Lymphoid cells derived from BALdisclosed an increased natural killer activity after IL-2 treatment, and TNF was increased in BAL fluid. Pulmonary function tests evidencedan increased alveolar-arterial difference for oxygen allied with a decrease of forced expiratory volume in 1 second, forced vital capacity,and carbon monoxide transfer coefficient consistent with a significant, albeit not clinically relevant, interstitial lung defect. Conclusion. Continuous-infusion IL-2 is feasible in patients with advanced lungcancer even outside an intensive care unit, but overall compliance ispoor. Although clinical pulmonary toxicity is negligible, small but statistically significant alterations of the pulmonary function are evident. In addition, this regimen produces a significant activation of the immune system at the pulmonary level.

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Documento generato il 03/04/20 alle ore 20:32:23