Journal of immunotherapy : official journal of the Society for Biological Therapy最新文献

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Treatment of hairy cell leukemia with granulocyte colony-stimulating factor and recombinant consensus interferon or recombinant interferon-alpha-2b. 粒细胞集落刺激因子联合重组共识干扰素或重组干扰素- α -2b治疗毛细胞白血病。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00007
J A Glaspy, L Souza, S Scates, M Narachi, L Blatt, J Ambersley, D W Golde
{"title":"Treatment of hairy cell leukemia with granulocyte colony-stimulating factor and recombinant consensus interferon or recombinant interferon-alpha-2b.","authors":"J A Glaspy,&nbsp;L Souza,&nbsp;S Scates,&nbsp;M Narachi,&nbsp;L Blatt,&nbsp;J Ambersley,&nbsp;D W Golde","doi":"10.1097/00002371-199204000-00007","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00007","url":null,"abstract":"<p><p>Patients with hairy cell leukemia and neutropenia (absolute neutrophil count less than 1.5 x 10(9)/L) were treated with recombinant granulocyte colony-stimulating factor (G-CSF) at doses of 3.6 and 7.2 micrograms/kg by daily subcutaneous injection, until normalization of neutrophil counts occurred. Patients then received either recombinant interferon-alpha-2b (r-IFN-alpha-2b) or a unique IFN, recombinant consensus IFN (rIFN-con-1), each given at doses of 10 micrograms/m2 subcutaneously three times a week, coupled with continued daily G-CSF therapy, for 3 months. After 3 months the G-CSF was discontinued; patients continued to take IFN for 1 year. All 10 patients responded to G-CSF with normalization of neutrophil counts within 2 weeks; the increase in neutrophil counts was greater in previously splenectomized patients. Four patients were treated with r-IFN-alpha-2b, and six were treated with rIFN-con-1. No patients developed recurrent neutropenia with the initiation of IFN therapy. Nine patients are evaluable for response to IFN. Five of six patients demonstrated hematologic improvement with rIFN-con-1, with two patients obtaining complete responses. All three patients receiving r-IFN-alpha-2b demonstrated hematologic improvement; one complete response was observed. Toxicities of both IFNs included influenza-like symptoms. We conclude that G-CSF can abrogate the myelosuppressive effects of IFN, and may be a useful adjunct to this therapy in neutropenic patients. We conclude that rIFN-con-1, the product of a synthetic gene, has activity in the treatment of hairy cell leukemia, and merits clinical investigation in other settings.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"198-208"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12553996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 一项西南肿瘤组的ⅰ期研究:重组干扰素- γ和重组白细胞介素-2序贯联合治疗癌症患者。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00004
C W Taylor, E M Chase, R P Whitehead, J J Rinehart, J A Neidhart, R Gonzalez, P A Bunn, E M Hersh
{"title":"A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer.","authors":"C W Taylor,&nbsp;E M Chase,&nbsp;R P Whitehead,&nbsp;J J Rinehart,&nbsp;J A Neidhart,&nbsp;R Gonzalez,&nbsp;P A Bunn,&nbsp;E M Hersh","doi":"10.1097/00002371-199204000-00004","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00004","url":null,"abstract":"<p><p>Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"176-83"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12685505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Growth inhibition of human colorectal carcinoma cell lines by tumor necrosis factor-alpha correlates with reduced activity of pp60c-src. 肿瘤坏死因子- α对人结直肠癌细胞系生长的抑制作用与pp60c-src活性降低相关。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00002
C L Novotny-Smith, G E Gallick
{"title":"Growth inhibition of human colorectal carcinoma cell lines by tumor necrosis factor-alpha correlates with reduced activity of pp60c-src.","authors":"C L Novotny-Smith,&nbsp;G E Gallick","doi":"10.1097/00002371-199204000-00002","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00002","url":null,"abstract":"<p><p>One molecular alteration that has been observed in the majority of colorectal carcinomas is the activation of pp60c-src kinase. To address the role of pp60c-src in growth control of colon carcinoma cell lines, the effects of the biologic response modifier, tumor necrosis factor (TNF)-alpha were studied on the established HT29 colorectal carcinoma cell line and two clonal variants derived from the parental line. In one clone, HT29-A34, approximately 55% growth inhibition was observed following a 120-h incubation period with 10(3) U/ml TNF. In this TNF-sensitive cell line, pp60c-src immune complex kinase activity was reduced 3.9-fold accompanied by only a slight reduction in pp60c-src protein levels. Growth inhibition and decreased pp60c-src kinase activity correlated in a dose-dependent manner. The HT29-A14 TNF-resistant clone was not growth-inhibited by TNF, and no changes in pp60c-src were observed following treatment. Growth inhibition also correlated with reduced pp60c-src kinase specific activity in a number of other established colon carcinoma cell lines that were TNF-sensitive. In TNF-resistant colon carcinoma cell lines, pp60c-src kinase activity and levels remained unchanged. When changes in specific activity of pp60c-src were observed in sensitive cells, they occurred after decreased [3H]-thymidine uptake was observed. Therefore, these changes in pp60c-src activity are not the earliest event in TNF-induced growth inhibition. Nevertheless, our results suggest that modulation of pp60c-src kinase activity may be important in growth control of colorectal carcinoma cell lines.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"159-68"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12553995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer. 在晚期癌症患者中,白细胞介素-2与干扰素- γ剂量增加有关。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00009
P Viens, D Blaise, A M Stoppa, M Brandely, D Baume, D Olive, M Resbeut, J R Delpero, M Lopez, C Aubert
{"title":"Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer.","authors":"P Viens,&nbsp;D Blaise,&nbsp;A M Stoppa,&nbsp;M Brandely,&nbsp;D Baume,&nbsp;D Olive,&nbsp;M Resbeut,&nbsp;J R Delpero,&nbsp;M Lopez,&nbsp;C Aubert","doi":"10.1097/00002371-199204000-00009","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00009","url":null,"abstract":"<p><p>Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"218-24"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12683499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Reversible cardiomyopathy after high-dose interleukin-2 therapy. 高剂量白介素-2治疗后的可逆性心肌病。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00010
M Goel, L Flaherty, S Lavine, B G Redman
{"title":"Reversible cardiomyopathy after high-dose interleukin-2 therapy.","authors":"M Goel,&nbsp;L Flaherty,&nbsp;S Lavine,&nbsp;B G Redman","doi":"10.1097/00002371-199204000-00010","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00010","url":null,"abstract":"<p><p>We observed two patients who developed moderate global myocardial dysfunction during therapy with high-dose interleukin-2 (IL-2). Although cardiac enzymes became markedly elevated at the completion of a full course of IL-2, patients exhibited no ischemic symptoms. Serial echocardiography documented global myocardial dysfunction, which resolved in 5 days in one patient but persisted beyond 4 weeks in another. Asymptomatic reversible myocardial injury can occur with high-dose IL-2 and can persist beyond 4 weeks after stopping therapy. Review of the literature suggests an IL-2-associated myocarditis as an etiology.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"225-9"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12683500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Renal cell carcinoma treated with continuous-infusion interleukin-2 with ex vivo-activated killer cells. 体外活化杀伤细胞持续输注白介素-2治疗肾细胞癌。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00005
K A Foon, P J Walther, Z P Bernstein, L Vaickus, R Rahman, H Watanabe, J Sweeney, J Park, D Vesper, D Russell
{"title":"Renal cell carcinoma treated with continuous-infusion interleukin-2 with ex vivo-activated killer cells.","authors":"K A Foon,&nbsp;P J Walther,&nbsp;Z P Bernstein,&nbsp;L Vaickus,&nbsp;R Rahman,&nbsp;H Watanabe,&nbsp;J Sweeney,&nbsp;J Park,&nbsp;D Vesper,&nbsp;D Russell","doi":"10.1097/00002371-199204000-00005","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00005","url":null,"abstract":"<p><p>High-dose recombinant interleukin-2 (rIL-2) results in tumor responses in patients with metastatic renal cell carcinoma ranging from 9 to 31%. Continuous infusion regimens of rIL-2 may be less toxic and may result in greater in vivo lymphokine-activated killer (LAK) cell production. The current trial used a continuous infusion of rIL-2 with ex vivo LAK cells. These cells were pretreated with phenylalanine methyl ester to remove monocytes to allow cell culture at higher concentrations. Twenty-three patients were entered into the trial. Two patients had complete responses (9%) lasting 15+ and 20+ months. Four patients had partial responses (17%) of 9+, 6+, 3, and 3 months, respectively. One partial responder at 9+ months had only minimal residual retroperitoneal disease that may represent scar tissue. All responders had prior nephrectomies. All but one of the responding patients completed a full cycle of rIL-2 at the highest (starting) dose, 6 x 10(6) U/m2. This rIL-2/LAK regimen appears to be an effective therapy for metastatic renal cell carcinoma.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"184-90"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12683496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Enhancement of lymphokine-activated killer activity induction in vitro by interleukin-1 administered in patients with urological malignancies. 白细胞介素-1对泌尿系统恶性肿瘤患者体外淋巴因子激活杀伤活性诱导的增强作用。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-04-01 DOI: 10.1097/00002371-199204000-00006
K Marumo, M Tachibana, N Deguchi, H Tazaki
{"title":"Enhancement of lymphokine-activated killer activity induction in vitro by interleukin-1 administered in patients with urological malignancies.","authors":"K Marumo,&nbsp;M Tachibana,&nbsp;N Deguchi,&nbsp;H Tazaki","doi":"10.1097/00002371-199204000-00006","DOIUrl":"https://doi.org/10.1097/00002371-199204000-00006","url":null,"abstract":"<p><p>We have evaluated the synergistic effects of interleukin-1 (IL-1) and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) activity. Subcutaneous injection of recombinant IL-1 beta at an initial dose of 1 x 10(4) U was given to nine patients (five with renal cell carcinoma, two with bladder carcinoma, one with renal pelvic tumor, one with testicular tumor) on days 1 and 2 weekly for 4 weeks. The dose was increased weekly up to 4 x 10(4) U, if it was well tolerated. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in the 2nd and 4th weeks, and LAK activity of PBMC against Daudi cells was measured using a 4-h 51Cr-release assay at an effector:target cell ratio of 20:1, after incubation with 50 U/ml of recombinant IL-2 for 72 h. Proliferation of PBMC was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 h. IL-2 receptor (IL-2R)-positive cells in PBMC were enumerated using monoclonal antibody and flow cytometry. Mean values of LAK activity induced by IL-2 were significantly augmented after administration of IL-1 beta (p less than 0.01). IL-1 beta, however, did not enhance proliferation of PBMC caused by IL-2, nor did it increase the number of IL-2R-positive cells in peripheral blood lymphocytes of the patients. Results suggest that combination of IL-1 and IL-2 has synergistic antitumor activity in treatment of malignant diseases.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 3","pages":"191-7"},"PeriodicalIF":0.0,"publicationDate":"1992-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199204000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12683497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
A phase I trial of recombinant human macrophage colony-stimulating factor by rapid intravenous infusion in patients with refractory malignancy. 重组人巨噬细胞集落刺激因子快速静脉输注治疗难治性恶性肿瘤的I期临床试验。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-02-01 DOI: 10.1097/00002371-199202000-00004
K W Zamkoff, J Hudson, E S Groves, A Childs, M Konrad, A R Rudolph
{"title":"A phase I trial of recombinant human macrophage colony-stimulating factor by rapid intravenous infusion in patients with refractory malignancy.","authors":"K W Zamkoff,&nbsp;J Hudson,&nbsp;E S Groves,&nbsp;A Childs,&nbsp;M Konrad,&nbsp;A R Rudolph","doi":"10.1097/00002371-199202000-00004","DOIUrl":"https://doi.org/10.1097/00002371-199202000-00004","url":null,"abstract":"<p><p>Twenty patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant macrophage colony-stimulating factor (rM-CSF). The rM-CSF was administered by intravenous bolus infusion for 5 consecutive days every other week for 2 treatment weeks. The doses administered ranged from 30 to 33,000 micrograms/m2/day. There was no intrapatient dose escalation. There were minimal to no systemic side effects seen, except for acute dyspnea noted in three patients. The dyspnea was felt to be related to the rate of infusion and did not recur in one patient given additional rM-CSF at a slower infusion rate. The major hematologic effect seen was a mild decrease in platelet count, which began to recover while the patients continued to receive the rM-CSF. The clearance of rM-CSF was dose dependent. Lower doses resulted in a saturable mechanism felt to represent cellular uptake. Clearance at higher doses demonstrated both a first-order mechanism at high serum rM-CSF concentrations, representing renal clearance, as well as a saturable mechanism at low serum concentrations. The maximum mean serum half-life was reached at dose levels of greater than or equal to 3,690 micrograms/m2 and was in the range of 234-258 min. By this route of administration, rises in absolute monocyte count were slight and seen only at doses of greater than or equal to 450 micrograms/m2 during the second therapy week. The maximum tolerated dose was not reached in this study because of lack of availability of rM-CSF.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 2","pages":"103-10"},"PeriodicalIF":0.0,"publicationDate":"1992-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199202000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12738892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 27
Phase I trial of recombinant interleukin-2 followed by recombinant tumor necrosis factor in patients with metastatic cancer. 重组白细胞介素-2和重组肿瘤坏死因子在转移性癌症患者中的I期临床试验。
Journal of immunotherapy : official journal of the Society for Biological Therapy Pub Date : 1992-02-01 DOI: 10.1097/00002371-199202000-00003
M S Negrier, C N Pourreau, P A Palmer, J Y Ranchere, A Mercatello, P Viens, D Blaise, C Jasmin, J L Misset, C R Franks
{"title":"Phase I trial of recombinant interleukin-2 followed by recombinant tumor necrosis factor in patients with metastatic cancer.","authors":"M S Negrier,&nbsp;C N Pourreau,&nbsp;P A Palmer,&nbsp;J Y Ranchere,&nbsp;A Mercatello,&nbsp;P Viens,&nbsp;D Blaise,&nbsp;C Jasmin,&nbsp;J L Misset,&nbsp;C R Franks","doi":"10.1097/00002371-199202000-00003","DOIUrl":"https://doi.org/10.1097/00002371-199202000-00003","url":null,"abstract":"<p><p>In this Phase I trial, the feasibility of sequential administration of continuous intravenous recombinant interleukin-2 (rIL-2) at 18 x 10(6) IU/m2/day for 6 days, followed by three daily bolus intravenous recombinant tumor necrosis factor (rTNF) infusions at doses escalating between 10 and 120 micrograms/m2/day, was investigated in 31 patients with metastatic malignancies. Prophylactic use of indomethacin prior to and during rTNF administration was found to significantly reduce toxicity. However, despite prophylactic indomethacin, a maximum tolerated dose of rTNF of 120 micrograms/m2 was reached. The limiting toxicity was hypotension. Predictable flu-like toxicities (i.e., fever/chills, hypotension, gastrointestinal toxicity, edema, malaise) were seen in most patients. These started during the rIL-2 infusion and continued during rTNF administration, particularly in the absence of indomethacin. Hematological, renal, and hepatic toxicities were not dose limiting. These toxicities were all reversible after treatment interruption. Pulmonary toxicity [i.e., anaphylactic-like reactions, bronchospasms, and adult respiratory distress syndrome (ARDS)] was seen in several patients immediately after rTNF infusions, irrespective of the rTNF dose or treatment cycle, and mainly in patients with extensive pulmonary metastases. The combined effect of treatment-related ARDS, lung metastases, and a Guillain-Barré syndrome led to the death of one patient. Two partial responses were seen in this study (i.e., breast and renal cancer). Based on these results, a Phase II trial of rIL-2 followed by rTNF has been initiated in metastatic breast cancer patients.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 2","pages":"93-102"},"PeriodicalIF":0.0,"publicationDate":"1992-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199202000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12738896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 26
Serum CD25 levels during interleukin-2 therapy: dose dependence and correlations with clinical toxicity and lymphocyte surface sCD25 expression. 白细胞介素-2治疗期间血清CD25水平:剂量依赖性及与临床毒性和淋巴细胞表面sCD25表达的相关性
M P Bogner, S D Voss, R Bechhofer, J A Hank, M Roper, D Poplack, D Hammond, P M Sondel
{"title":"Serum CD25 levels during interleukin-2 therapy: dose dependence and correlations with clinical toxicity and lymphocyte surface sCD25 expression.","authors":"M P Bogner,&nbsp;S D Voss,&nbsp;R Bechhofer,&nbsp;J A Hank,&nbsp;M Roper,&nbsp;D Poplack,&nbsp;D Hammond,&nbsp;P M Sondel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Using an enzyme-linked immunosorbent assay (ELISA), we have measured serum levels of a soluble form of the p55 subunit of the interleukin-2 receptor complex, soluble CD25 (sCD25), at regular intervals in the sera of 51 pediatric and adult cancer patients receiving recombinant human interleukin-2 (IL-2). The IL-2 was administered in repetitive weekly cycles alone or in combination with lymphokine-activated killer (LAK) cells. Levels of CD25 correlated with clinical toxicities reflected by nadir blood pressures, percentages of weight gained, and minimum Karnofsky performances during IL-2 therapy. Coadministration of autologous in vitro activated LAK cells together with IL-2 did not significantly affect the pattern of sCD25 release relative to administration of IL-2 alone. Examination of sCD25 release in response to different doses of IL-2 revealed a statistically significant dose effect of IL-2 on the sCD25 levels in patient sera. In addition, the level of sCD25 in patient sera also correlated strongly with expression of CD25 on the surface of peripheral blood lymphocytes (PBL) obtained from patients following IL-2 therapy. These studies demonstrate the utility of the sCD25 ELISA as a clinical tool for monitoring patients on treatment regimens that include IL-2.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"11 2","pages":"111-8"},"PeriodicalIF":0.0,"publicationDate":"1992-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12738893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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