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Cytokine replacement in patients with HIV-1 non-Hodgkin's lymphoma: the rationale for low-dose interleukin-2 therapy. 细胞因子替代治疗HIV-1非霍奇金淋巴瘤患者:低剂量白细胞介素-2治疗的基本原理
M H Shah, R A Baiocchi, T A Fehniger, V P Khatri, M Gould, B Poiesz, Z P Bernstein, M A Caligiuri
{"title":"Cytokine replacement in patients with HIV-1 non-Hodgkin's lymphoma: the rationale for low-dose interleukin-2 therapy.","authors":"M H Shah,&nbsp;R A Baiocchi,&nbsp;T A Fehniger,&nbsp;V P Khatri,&nbsp;M Gould,&nbsp;B Poiesz,&nbsp;Z P Bernstein,&nbsp;M A Caligiuri","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The drastic increase in the incidence of non-Hodgkin's lymphoma in patients infected with HIV-1 is testimony to the fact that our immune system is critical for the prevention of certain malignancies. Preclinical and clinical studies were conducted to (1) gain further insight into defects in immunity that can lead to malignant transformation and (2) determine if certain immune deficiencies could be corrected by cytokines delivered at doses that result in near-physiologic concentrations in vivo.</p><p><strong>Methods: </strong>We have used the severe combined immune deficient mouse engrafted with human peripheral blood leukocytes from healthy individuals who are seropositive for the Epstein-Barr virus to study the spontaneous development of malignant Epstein-Barr virus-positive human B-cell lymphoproliferative disorder.</p><p><strong>Results: </strong>We have demonstrated in this model that, in the absence of CD4+ T cells, cytokine replacement with low-dose interleukin (IL)-2 therapy can prevent Epstein-Barr virus-positive human B-cell lymphoproliferative disorder by interacting with mouse natural killer and human CD8+ T cells. We review our clinical experience with administration of low-dose IL-2 therapy in patients with HIV-1-related cancer, noting minimal toxicity and significant immune modulation. We provide evidence that this therapy can favorably alter the type 1 cytokine profile in vivo in these patients, and improve the cellular response to infectious insults in vitro.</p><p><strong>Conclusion: </strong>Early clinical studies with low-dose IL-2 therapy in patients with HIV-1-related lymphoma suggest that this therapy may have a role in the prevention and treatment of this disease.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S45-51"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21539418","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
Renal cell carcinoma: current status and future plans. 肾细胞癌:现状和未来计划。
R A Figlin
{"title":"Renal cell carcinoma: current status and future plans.","authors":"R A Figlin","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S52-4"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21539419","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
Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer. 白细胞介素-2与癌症患者免疫治疗的发展。
S A Rosenberg
{"title":"Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer.","authors":"S A Rosenberg","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S2-7"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21540152","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
Long-term follow-up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin-2 in Europe. 欧洲静脉注射重组白细胞介素-2治疗转移性肾细胞癌患者的长期随访
S Negrier, J Maral, M Drevon, J Vinke, B Escudier, T Philip
{"title":"Long-term follow-up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin-2 in Europe.","authors":"S Negrier,&nbsp;J Maral,&nbsp;M Drevon,&nbsp;J Vinke,&nbsp;B Escudier,&nbsp;T Philip","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The median survival for patients with metastatic renal cell carcinoma (mRCC) is generally < 1 year. Immunotherapy with high-dose recombinant interleukin (IL)-2 has been reported to produce objective responses in approximately 15% of treated patients and is associated with durable complete responses and prolonged survival in responding patients. The impact of IL-2 therapy on survival of metastatic renal cell carcinoma patients has begun to emerge, based on long-term follow-up data from large databases. Combinations of IL-2 and interferon alfa (IFN-alpha) have also been intensively investigated in mRCC.</p><p><strong>Patients and methods: </strong>Between 1987 and 1990, 281 mRCC patients were treated with continuous infusion IL-2 in three European multinational, single-arm phase II trials. Long-term treatment outcomes for these patients were analyzed, and the results are presented here. The results of a large, randomized French cooperative group trial (the Cancer Renal Cytokine [CRECY] study) that enrolled 425 patients between 1991 and 1995 are also summarized. Patients on this trial were randomized to treatment with IL-2 alone, IFN-alpha alone, or the combination.</p><p><strong>Results: </strong>Among patients included in the 281-patient database, the objective response rate was 15%. Median survival was 10 months; 41% of patients were alive at 1 year, 22% were alive at 2 years, and 8% were alive at 5 years. Among patients with a complete or partial response, 60% and 18% were alive at 5 years, respectively. No clinical factors were predictive for response or survival; however, no patient with a high endogenous IL-6 level at diagnosis responded to IL-2 therapy. The CRECY trial demonstrated that the combination of IL-2 and IFN-alpha induced a significantly higher response rate (P < 0.01) and significantly improved 1-year event-free survival (P = 0.01) compared with either agent alone, but overall survival was not significantly different between the three treatment groups.</p><p><strong>Conclusion: </strong>The European experience suggests that the 5-year survival rate for metastatic renal cell carcinoma patients treated with high-dose continuous infusion IL-2 therapy is approximately 8% and that the majority of the therapeutic benefit is restricted to patients achieving a complete response. Therefore, given the toxicity, candidates for IL-2 therapy should be carefully selected. The combination of IL-2 and IFN-alpha does not appear to provide additional survival benefit. Efforts to further improve therapeutic outcome for patients with metastatic renal cell carcinoma should focus on understanding the underlying mechanisms of cytokine-induced tumor regression.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S93-8"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21538788","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
High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. 转移性黑色素瘤患者的高剂量重组白细胞介素-2治疗:长期生存更新
M B Atkins, L Kunkel, M Sznol, S A Rosenberg
{"title":"High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update.","authors":"M B Atkins,&nbsp;L Kunkel,&nbsp;M Sznol,&nbsp;S A Rosenberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To update response duration and survival data for patients with metastatic melanoma receiving the high-dose IV bolus recombinant interleukin (IL)-2 regimen.</p><p><strong>Patients and methods: </strong>Two hundred seventy assessable patients were entered into eight clinical trials conducted between 1985 and 1993. IL-2 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second, identical cycle of treatment was scheduled following 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Responding patients received up to five courses (two cycles/course) of treatment. All data were updated through December 1998 using report forms completed by the clinical investigators.</p><p><strong>Results: </strong>The objective overall response rate was unchanged from the previous report. Tumor responses were seen in 16% of patients, with complete responses in 17 (6%) and partial responses in 26 (10%). Median survival for the group as a whole is now 12 months. Median follow-up time for surviving patients exceeds 7 years. Median duration of response for the 43 responding patients and the 26 patients with partial responses remained unchanged at 8.9 and 5.9 months, respectively. Response durations ranged from 1.5 to > 122 months. The median duration of complete responses has yet to be reached, but is at least 59 months. Thirty-one patients (11%) were alive as of last contact; 28 were confirmed, including 18 responding patients. Three patients were lost to follow-up at > 1, > 13, and > 104 months. Twelve responding patients remained continually disease- or progression-free from > 70 to > 150 months following initiation of therapy. Disease progression was not observed in any patient who was responding as of the last report or in any patient responding for longer than 30 months.</p><p><strong>Conclusion: </strong>These data continue to support the notion that high-dose IL-2 produces durable responses in some patients with metastatic melanoma and should be considered a therapeutic option for appropriately selected patients with this disease.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S11-4"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21540154","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
The role of interleukin-2 in the management of stage IV melanoma: the EORTC melanoma cooperative group program. 白细胞介素-2在IV期黑色素瘤治疗中的作用:EORTC黑色素瘤合作小组项目。
U Keilholz, A M Eggermont
{"title":"The role of interleukin-2 in the management of stage IV melanoma: the EORTC melanoma cooperative group program.","authors":"U Keilholz,&nbsp;A M Eggermont","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To review the current information available from the European Organization for Research and Treatment of Cancer (EORTC) programs on the use of interleukin (IL)-2 in stage IV melanoma patients.</p><p><strong>Patients and methods: </strong>A database from 631 patients treated within 27 trials with high-dose IL-2-based regimens was compiled to develop hypotheses and valid stratification factors for randomized trials. Subsequently, 126 patients were enrolled in a trial evaluating interferon alfa (IFN-alpha) and IL-2 with or without cisplatin, and 325 patients were enrolled in an ongoing EORTC trial (18951) to evaluate dacarbazine, cisplatin, and IFN-alpha, with or without IL-2.</p><p><strong>Results: </strong>The database suggests long-term survival rates of 23% and a 5-year survival rate of 13% for patients receiving a combination of IFN-alpha and IL-2 with or without chemotherapy. The addition of chemotherapy improved response rate but not survival. The first randomized trial testing the role of cisplatin in a chemoimmunotherapy regimen for advanced melanoma revealed a palliative effect for cisplatin but no survival benefit. The current trial (EORTC 18951), which is testing the impact of IL-2 on survival, is still immature. In the translational research program, we have evidence that patients in continuous complete remission after IL-2-based treatment have evidence of residual disease by polymerase chain reaction assay and, at the same time, melanoma-reactive T cells are present in the peripheral blood.</p><p><strong>Conclusion: </strong>Mature results defining the role and, to some extent, the mechanism of IL-2 in advanced melanoma are emerging.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S99-103"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21538789","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
Overview of interleukin-2 inhalation therapy. 白细胞介素-2吸入疗法综述。
E Huland, H Heinzer, H Huland, R Yung
{"title":"Overview of interleukin-2 inhalation therapy.","authors":"E Huland,&nbsp;H Heinzer,&nbsp;H Huland,&nbsp;R Yung","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Locoregional administration of interleukin (IL)-2, which acts physiologically as a local hormone, is an effective therapeutic modality. Diverse preclinical and clinical models have described methods of administration that expose tumor tissues to continuously high levels of cytokines. Regional administration of IL-2 that does not raise intravascular IL-2 levels induces local and systemic immunomodulation and produces objective local tumor responses. Most importantly, regional therapy is much less toxic than systemic IL-2 therapy.</p><p><strong>Patients and methods: </strong>We review clinical experiences using inhaled IL-2 therapy for the treatment of pulmonary metastases in roughly 300 patients with a variety of primary tumors. This includes our own 10-year single-institution experience with inhaled IL-2 therapy in the treatment of 188 metastatic renal cell carcinoma patients with progressive pulmonary metastases. Patients in our clinic are treated with 18 to 36 million IU of recombinant IL-2, administered 90% by inhalation and 10% subcutaneously, until disease progression. A variety of doses and schedules of inhaled IL-2 have been investigated alone and in combination with systemic therapies.</p><p><strong>Results: </strong>Inhalation of IL-2 has been reported to prevent progression of pulmonary and mediastinal metastases of metastatic renal cell carcinoma, breast and ovarian carcinoma, and melanoma. Inhaled IL-2 alone is well tolerated; a dose-dependent cough is the major adverse event. A significant dose-dependent increase in lymphocytes and eosinophils has been observed in bronchoalveolar lavage in patients and animals. Dose and schedule can influence outcome. In a phase I trial using inhaled IL-2 alone in patients with a variety of primary malignancies, once-daily inhalation of IL-2 at doses up to 15 million IU/m2 was well tolerated but did not result in prolonged stabilization of pulmonary disease. In a multidose phase I trial, using 5-times-daily inhalation of natural IL-2, pulmonary lesions in three of 14 (21%) metastatic renal cell carcinoma patients responded, and a similar multicenter trial demonstrated a 29% response rate. Among 188 metastatic renal cell carcinoma patients treated with inhaled recombinant IL-2 at the Clinic Eppendorf, progression of pulmonary metastases was prevented in 68% of patients for a median duration of 7 months, and overall survival was significantly improved compared with expected survival (Elson's risk analysis; 17.2 vs 5.3 mo). All patients, including high-risk patients, appeared to benefit. Encouraging results have also been reported in patients with metastatic melanoma and gynecologic tumors when inhaled IL-2 was used as second-line therapy to treat pulmonary metastases.</p><p><strong>Conclusions: </strong>The efficacy of inhaled IL-2, alone or in combination with systemic immunotherapy, immunochemotherapy, or chemotherapy, has been documented in a variety of malignancies. All","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S104-12"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21538790","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
Expanding the indications for surgery and adjuvant interleukin-2-based immunotherapy in patients with advanced renal cell carcinoma. 扩大手术适应症和辅助白介素-2免疫治疗晚期肾细胞癌患者。
A Belldegrun, O Shvarts, R A Figlin
{"title":"Expanding the indications for surgery and adjuvant interleukin-2-based immunotherapy in patients with advanced renal cell carcinoma.","authors":"A Belldegrun,&nbsp;O Shvarts,&nbsp;R A Figlin","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the role of surgery and adjuvant interleukin (IL)-2-based immunotherapy in the treatment of patients with advanced metastatic renal cell carcinoma</p><p><strong>Patients and methods: </strong>The survival of 354 consecutive patients with metastatic renal cell carcinoma treated with IL-2-based immunotherapy through the UCLA Medical Center Kidney Cancer Program was analyzed There were five groups of patients. Patients who initially presented with metastatic disease received either (1) IL-2 therapy with primary tumor in place; (2) nephrectomy followed by IL-2 therapy, or (3) nephrectomy followed by immunotherapy with IL-2 plus tumor-infiltrating lymphocytes. Patients who underwent nephrectomy for localized disease were divided into two groups: (4) those who developed metastatic disease > or = 6 months after nephrectomy and then received IL-2 therapy; and (5) those who developed metastatic disease < 6 months after nephrectomy and then received IL-2 therapy. Kaplan-Meier survival curves were generated for all patient groups.</p><p><strong>Results: </strong>Among patients who received IL-2-based immunotherapy with their primary tumor in place (group 1; n = 36), 1- and 2-year survival rates were 29% and 4%, respectively, compared with 1- and 2-year survival rates of 67% and 44%, respectively, for all similar patients who underwent nephrectomy prior to IL-2 therapy (n = 235). Among patients initially presenting with metastatic disease who underwent nephrectomy followed by IL-2 therapy without tumor-infiltrating lymphocytes (group 2; n = 69), the 1- and 2-year survival rates were 53% and 25%, respectively. The best survival was observed in patients treated with nephrectomy followed by IL-2 plus tumor-infiltrating lymphocyte therapy (group 3; n = 102), which yielded 1- and 2-year survival rates of 73% and 55%, respectively. Among patients initially undergoing nephrectomy for localized disease, patients receiving IL-2-based therapy for subsequent metastasis > or = 6 months following nephrectomy (group 4; n = 128) had 1- and 2-year survival rates of 64% and 40%, respectively, compared with 45% and 15%, respectively, for patients developing metastasis < 6 months after nephrectomy (group 5; n = 19).</p><p><strong>Conclusion: </strong>The role of surgery prior to IL-2-based immunotherapy remains controversial Our data demonstrate that aggressive surgery is safe, causing minimal morbidity despite extensive tumor involvement, and significantly improves survival outcomes in patients with metastatic renal cell carcinoma when carried out in conjunction with an IL2-based immunotherapy regimen.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S88-92"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21538787","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
Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. 肾细胞癌患者高剂量重组白细胞介素-2的长期生存更新。
R I Fisher, S A Rosenberg, G Fyfe
{"title":"Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma.","authors":"R I Fisher,&nbsp;S A Rosenberg,&nbsp;G Fyfe","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To update response duration and survival data for patients with metastatic renal cell carcinoma treated with high-dose interleukin (IL)-2.</p><p><strong>Patients and methods: </strong>Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Recombinant IL-2 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximal support. A second, identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. All data were updated as of December 1998, with report forms completed by the clinical investigators. These data had last been updated as part of the Food and Drug Administration reporting requirements in 1996.</p><p><strong>Results: </strong>Objective responses previously have been reported in 37 of 255 patients (15%) with 17 complete responses (7%) and 20 partial responses (8%). These data remain unchanged from previous reports. Median response duration for all objective responders remains unchanged at 54 months, but the range now extends from 3 to > 131 months. Median duration for all complete responses has not yet been reached, but was at least 80 months (range, 7- > 131 mo) at the time of this analysis. Median duration for all partial responses remains 20 months (range, 3- > 126 mo). Median survival time for all 255 patients remains 16.3 months, with 10% to 20% of patients estimated to be alive 5 to 10 years after treatment with high-dose IL-2.</p><p><strong>Conclusion: </strong>With prolonged follow-up, treatment with high-dose recombinant IL-2 remains extremely effective for a subset of patients with metastatic renal cell carcinoma.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S55-7"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21539420","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
Rationale for intergroup trial E-3695 comparing concurrent biochemotherapy with cisplatin, vinblastine, and DTIC alone in patients with metastatic melanoma. 组间试验E-3695比较转移性黑色素瘤患者同时使用顺铂、长春碱和DTIC进行生物化疗的基本原理。
L E Flaherty
{"title":"Rationale for intergroup trial E-3695 comparing concurrent biochemotherapy with cisplatin, vinblastine, and DTIC alone in patients with metastatic melanoma.","authors":"L E Flaherty","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The modest activity of chemotherapy and biologic agents in the treatment of advanced metastatic melanoma has prompted investigators to consider combinations of chemotherapy and biologic agents (i.e., biochemotherapy) as a way of improving response rates and survival. Although biochemotherapy has generated a great deal of interest over the last several years, and these regimens have produced high response rates in single-institution phase II trials, they have yet to demonstrate a significant survival benefit in randomized trials compared with either chemotherapy or biotherapy alone.</p><p><strong>Methods: </strong>The available literature regarding the clinical experience with single- and multiagent chemotherapy, immunotherapy, and biochemotherapy was reviewed.</p><p><strong>Results: </strong>Treatment of metastatic melanoma with either single-agent or combination chemotherapy regimens is clearly suboptimal; the majority of responses are partial and of short duration. In contrast, interleukin (IL)-2 produces long-term durable complete remission in a subset of patients. Over 1,000 patients have been treated with IL-2-based biochemotherapy regimens in single-institution phase II trials, and response rates have ranged from 40% to 60%. Most encouraging have been the durable responses observed in 10% to 20% of patients in most of these trials. Large databases, including two meta-analyses, have confirmed the substantial improvement in response rate associated with biochemotherapy regimens that include both IL-2 and interferon alfa (IFN-alpha) compared with chemotherapy or biotherapy alone. Biochemotherapy is currently being evaluated in randomized controlled trials to determine if this treatment strategy can provide a survival benefit compared with current standard treatments. A pilot study at Beth Israel Deaconess Medical Center has demonstrated the feasibility of administering a modification of a concurrent biochemotherapy regimen, initially described by Legha et al, consisting of cisplatin, vinblastine, and dacarbazine (CVD) plus IL-2 and IFN-alpha in the cooperative group setting.</p><p><strong>Conclusion: </strong>These studies provided the rationale for intergroup trial E-3695, which is currently randomizing patients to concurrent biochemotherapy with CVD plus IL-2 and IFN-alpha versus CVD alone.</p>","PeriodicalId":79462,"journal":{"name":"The cancer journal from Scientific American","volume":"6 Suppl 1 ","pages":"S15-20"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21540155","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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