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2.
Ann Oncol ; 17(10): 1533-8, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16873433

ABSTRACT

BACKGROUND: Both pemetrexed and gemcitabine have single-agent activity in bladder cancer, but the combination of these two drugs has not been previously evaluated for safety and efficacy in this disease. Thus, the objectives in the current study were to determine overall response rate (ORR), progression-free survival, overall survival and safety and toxicity in chemonaive patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was administered over 30 min i.v. on days 1 and 8, and pemetrexed 500 mg/m2 over 10 min i.v. on day 8 after gemcitabine, every 21 days. RESULTS: Sixty-four patients were enrolled, 11 female and 53 male, median age 65 years (range 38-81), median WHO performance status of 1. Visceral metastases were present in 55% of patients. ORR among 47 patients evaluable for response was 28% (95% CI 16% to 43%) and ORR for the intention-to-treat population was 20% (95% CI 11% to 32%) with three CR and 10 PR. Median response duration was 11.2 months and median overall survival 10.3 months (95% CI 8.1-14.6 months). CTC grade 3/4 hematologic toxicities included anemia (19%), thrombocytopenia (9%), neutropenia (38%), febrile neutropenia (17%) and neutropenic sepsis (3%). Grade 3/4 non-hematologic toxicities included elevated transaminases (12%), dyspnea (8%), fatigue (8%) and stomatitis (5%). There was one toxic death due to neutropenic sepsis. CONCLUSIONS: The combination of pemetrexed and gemcitabine had a manageable safety profile. However, efficacy was apparently not superior to that of single-agent gemcitabine.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Deoxycytidine/analogs & derivatives , Glutamates/administration & dosage , Guanine/analogs & derivatives , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease-Free Survival , Drug Administration Schedule , Female , Glutamates/adverse effects , Guanine/administration & dosage , Guanine/adverse effects , Humans , Male , Middle Aged , Neoplasm Metastasis/drug therapy , Pemetrexed , Survival Analysis , Urinary Bladder/pathology , Urinary Bladder Neoplasms/mortality , Urothelium/pathology , Gemcitabine
3.
Br J Cancer ; 90(6): 1156-62, 2004 Mar 22.
Article in English | MEDLINE | ID: mdl-15026795

ABSTRACT

A retrospective analysis was conducted on data from four open-label, nonrandomised, phase II trials of recombinant interleukin-2 (rIL-2) in patients with metastatic renal cell carcinoma to compare the safety and efficacy of administration by subcutaneous (s.c.) and continuous intravenous (c.i.v.) infusion (n=103 s.c. and n=225 c.i.v.). No statistically significant differences were found between the cohorts in terms of overall response rate (s.c.: 13.6% vs c.i.v.: 12.4%, P=0.77), response duration (s.c.: 9.8 months vs c.i.v.: 10.1 months, P=0.99), and overall survival (P=0.08). Compared with c.i.v. administration, more patients in the s.c. cohort experienced stable disease (50.5 vs 29.8%) and fewer underwent disease progression (35.0 vs 43.6%). Subcutaneous administration was associated with a significantly lower incidence of grade 3 or 4 adverse events (46 vs 76%; P<0.001), and fewer s.c. patients required dose reductions because of toxicity (20 vs 82%). At the doses and within the schedules tested, this comparative analysis did not detect any difference in efficacy between s.c. and c.i.v. administration of rIL-2 in terms of overall survival, duration of response and response rate in patients with metastatic renal cell carcinoma. However, s.c. delivery of rIL-2 was associated with improved tolerability.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/drug therapy , Interleukin-2/administration & dosage , Interleukin-2/adverse effects , Kidney Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/pathology , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Injections, Subcutaneous , Interleukin-2/therapeutic use , Kidney Neoplasms/pathology , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome
4.
Ugeskr Laeger ; 163(10): 1432-6, 2001 Mar 05.
Article in Danish | MEDLINE | ID: mdl-11257752

ABSTRACT

INTRODUCTION: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIALS AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. Most patients received radiotherapy to both sides of the neck as well as elective irradiation of the mucosal sites in nasopharynx, oropharynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The five-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51%, 48% and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The most important factor for neck control was nodal stage (5-year estimates 69% [N1], 58% [N2] and 30% [N3]). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared to patients treated at both neck and mucosa. At five years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; p = 0.05). The 5-year disease-specific survival estimates were 28% and 45%, respectively (p = 0.10). DISCUSSION: Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly fewer loco-regional failures compared to patients treated with ipsilateral techniques, but only a trend towards better survival. Determination of the optimal strategy in terms of loco-regional control, survival and morbidity requires a prospective randomized trial.


Subject(s)
Head and Neck Neoplasms/therapy , Lymphatic Metastasis , Neoplasms, Unknown Primary , Adolescent , Adult , Aged , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/therapy , Combined Modality Therapy , Denmark/epidemiology , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/secondary , Humans , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/radiotherapy , Male , Middle Aged , Neoplasms, Unknown Primary/diagnosis , Prognosis , Radiotherapy Dosage
5.
Melanoma Res ; 10(1): 66-77, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10711642

ABSTRACT

A phase II study was performed to evaluate the efficacy of cisplatin combined with interleukin-2 and interferon-alpha2b administered subcutaneously to patients with metastatic malignant melanoma (MMM). Between April 1994 and January 1999, 87 patients with MMM and a WHO performance status of < or = 2 were entered into the study. The first 42 patients had prophylactic cimetidine; the other 45 patients did not. An overall response rate of 27% was achieved in the 82 patients evaluable for response. The median response duration was 7.0 months (range 4.4-29.0 months). The median survival for all patients was 10.1 months (range 0.4-64.9+ months). Toxicity was substantial but generally manageable and usually reversed on dose reduction or temporary interruption of treatment. Two patients (2%) died of treatment-related toxicity. No difference in response or survival was seen in the patients treated with or without cimetidine. In multivariate analysis, lactate dehydrogenase level (P < 0.001), number of metastatic sites (P = 0.014) and performance status (P = 0.035) was shown to be independent prognostic factors for survival. This high dose interleukin-2 subcutaneous regimen resulted in a small fraction of long-term survivors. The response and survival results were not superior to other studies using lower and less toxic interleukin-2 doses.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Melanoma/drug therapy , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Cimetidine/administration & dosage , Cimetidine/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Female , Humans , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Interleukin-2/administration & dosage , Interleukin-2/adverse effects , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Male , Melanoma/pathology , Middle Aged , Prognosis , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Skin Neoplasms/secondary , Survival Rate
6.
Melanoma Res ; 10(6): 585-9, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11198481

ABSTRACT

Electric pulses can cause transient permeabilization of cell membranes (electroporation) and this can be utilized to increase the uptake of chemotherapy (electrochemotherapy). Preclinical studies have shown that in vivo electroporation causes transient shut down of blood flow both in normal and, in particular, malignant tissues. We report the successful palliation of a malignant melanoma patient with bleeding skin metastases using electrochemotherapy. In an on-going study of combined electrochemotherapy and low dose interleukin-2, one patient with bleeding skin metastases was included. Nine skin metastases, of which seven were ulcerated, were treated. After intratumoral bleomycin injection, needle electrodes with two arrays 4 mm apart were inserted into the tumours. Eight square wave electric pulses each 99 micros in duration and with an applied voltage to electrode distance ratio of 1.2 kV/cm were administered. In all the treated lesions, bleeding immediately stopped on administration of the electric pulses and did not recur. The treated metastases developed crusts and the lesions healed in a matter of weeks. Treatments were given under local anaesthesia, lasted a few minutes, and patient discomfort was brief and modest. In conclusion, we propose that electrochemotherapy should be considered for the palliation of haemorrhaging metastases as it is an efficient, tolerable, brief, outpatient, once-only treatment.


Subject(s)
Drug Therapy/methods , Electroporation/methods , Hemorrhage/therapy , Melanoma/therapy , Skin Neoplasms/therapy , Aged , Antibiotics, Antineoplastic/therapeutic use , Bleomycin/therapeutic use , Combined Modality Therapy , Hemorrhage/pathology , Humans , Interleukin-2/pharmacology , Male , Melanoma/pathology , Skin Neoplasms/pathology , Time Factors
7.
Ann Oncol ; 9(6): 657-60, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9681081

ABSTRACT

BACKGROUND: Approximately 5% of patients with testicular cancer harbour carcinoma in situ (CIS) in the contralateral testis. CIS will progress into invasive tumour in about 50% of cases within five years. The present study evaluated the effect of platinum containing chemotherapy on CIS. PATIENTS AND METHODS: Thirty-three patients with disseminated germ-cell cancer and biopsy proven CIS of the testis were evaluated. RESULTS: CIS had disappeared in the first follow-up biopsy in 30 patients. Six patients had a relapse of CIS with or without invasive cancer after 30, 31, 47, 51, 76 and 95 months from start of chemotherapy. Two relapses were among six patients who initially received cisplatin, vinblastine and bleomycine and four among 27 patients who initially received cisplatin, etoposide and bleomycine. The estimated cumulative risk of CIS five and 10 years after chemotherapy was 21% and 42%, respectively. The estimated cumulative incidence of spermatogenesis was 64% and 81% at five and 10 years of follow-up, respectively. CONCLUSION: Platinum containing chemotherapy may eradicate CIS. However, patients with CIS may develop invasive cancer in spite of chemotherapy. In the light of the present data, we recommend radiotherapy to the affected testicle in patients with CIS in the contralateral testis and in patients with bilateral testicular CIS. In patients with extragonadal disease and CIS in one testicle, orchiectomy of the affected testicle is recommended. In patients for whom future fertility is an important issue, follow-up including repeated biopsies can be offered for a period of at least 10 years.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma in Situ/drug therapy , Seminoma/drug therapy , Testicular Neoplasms/drug therapy , Adult , Aged , Biopsy , Biopsy, Needle , Bleomycin/administration & dosage , Carboplatin/administration & dosage , Carcinoma in Situ/mortality , Carcinoma in Situ/pathology , Cisplatin/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Humans , Male , Middle Aged , Orchiectomy , Prognosis , Retrospective Studies , Seminoma/mortality , Seminoma/pathology , Survival Rate , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Treatment Outcome , Vinblastine/administration & dosage
8.
Clin Sci (Lond) ; 95(1): 73-81, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9662488

ABSTRACT

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.


Subject(s)
Carcinoma, Renal Cell/therapy , Interleukin-2/administration & dosage , Kidney Neoplasms/therapy , Kidney/physiopathology , Sodium/metabolism , Water/metabolism , 6-Ketoprostaglandin F1 alpha/urine , Adult , Aged , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/physiopathology , Female , Glomerular Filtration Rate/drug effects , Hemodynamics/drug effects , Humans , Infusions, Intravenous , Iodine Radioisotopes , Kidney/metabolism , Kidney Neoplasms/metabolism , Kidney Neoplasms/physiopathology , Lithium/urine , Male , Middle Aged , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Statistics, Nonparametric , Technetium Tc 99m Pentetate , Thromboxane B2/urine , Vascular Resistance/drug effects
9.
Eur J Cancer ; 29A(3): 347-50, 1993.
Article in English | MEDLINE | ID: mdl-8398332

ABSTRACT

34 patients with metastatic or recurrent transitional cell carcinoma (TCC) of the urothelium were treated with cisplatin 100 mg/m2 plus methotrexate 250 mg/m2 with folinic acid rescue every 3 weeks. A response rate of 55% was achieved with two complete and 15 partial responses in 31 evaluable patients. The overall median survival was 7 months, 9 months for responding and 4 months for non-responding patients. Toxicity was generally moderate. However, 1 patient with previous infectious problems died of neutropenic sepsis. Overall, 83% of the scheduled doses of cisplatin and 96% of the scheduled doses of methotrexate were given. In conclusion, this schedule of the combination of cisplatin and methotrexate did not improve response rate or survival compared with previous studies of this two-drug combination.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Urinary Bladder Neoplasms/drug therapy , Adult , Aged , Cisplatin/administration & dosage , Female , Humans , Leucovorin/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy
10.
Ugeskr Laeger ; 154(28): 1949-53, 1992 Jul 06.
Article in Danish | MEDLINE | ID: mdl-1509557

ABSTRACT

About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public.


Subject(s)
Melanoma/epidemiology , Skin Neoplasms/epidemiology , Denmark/epidemiology , Drug Therapy, Combination , Female , Humans , Incidence , Male , Melanoma/diagnosis , Melanoma/therapy , Prognosis , Risk Factors , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy
11.
J Clin Oncol ; 10(5): 753-9, 1992 May.
Article in English | MEDLINE | ID: mdl-1569448

ABSTRACT

PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2 (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients with CR was 209 and 715+ days, and for those with PR 161, 197, 245, and 353 days. Seven patients had stable disease (SD) with a median duration of 261 days (range, 127 to 381 days). The overall median survival was 261 days (range, 13 to 905+ days). The most frequent toxicities requiring dose reductions of rIL-2 were: hypotension in 87% of patients, dyspnea in 32%, CNS toxicity in 55%, and an increase in serum creatinine levels in 48%. Septicemia occurred in 16% of patients. Toxicities usually reversed on interruption of rIL-2 infusion. One patient (3%) died as a result of the treatment from initial CNS toxicity followed by multiorgan failure. CONCLUSIONS: The study confirmed the antitumor efficacy of rIL-2 administered by continuous infusion in patients with metastatic RCC. The response rate was similar to that obtained by high-dose bolus injections of rIL-2. Toxicity was substantial but manageable in a specialized oncology ward without routine use of an intensive care unit.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Interleukin-2/therapeutic use , Kidney Neoplasms/drug therapy , Adult , Aged , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/secondary , Drug Evaluation , Female , Humans , Infusions, Intravenous , Interleukin-2/adverse effects , Kidney Neoplasms/pathology , Male , Middle Aged , Radiography , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Treatment Outcome
12.
Cytokine ; 4(2): 144-50, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1633263

ABSTRACT

The purpose of this study was to examine the production of IL-1 beta, IL-6 and TNF-alpha by peripheral blood mononuclear cells in patients with renal cell carcinoma treated with recombinant interleukin 2 (rIL-2). Peripheral blood mononuclear cells (PBMC) were purified from blood samples obtained six times during therapy and the production of IL-1 beta, IL-6 and TNF-alpha were determined after 18 h culture of the PBMC in culture medium or in medium containing 10 micrograms lipopolysaccharide (LPS)/ml, 10 ng LPS/ml or 1000 units rIL-2/ml. In vivo therapy with rIL-2 resulted in substantial changes in the production of the three cytokines. Only the production of TNF-alpha following in vitro stimulation with rIL-2 was related to the clinical response, being significant lower in responding patients than in non-responders (P less than 0.05). These findings suggest that the rIL-2-induced TNF-alpha production of PBMC in vitro is lower in renal cancer patients that respond to rIL-2 therapy than in non-responding patients.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Interleukin-1/biosynthesis , Interleukin-2/therapeutic use , Interleukin-6/biosynthesis , Kidney Neoplasms/drug therapy , Leukocytes, Mononuclear/drug effects , Tumor Necrosis Factor-alpha/biosynthesis , Carcinoma, Renal Cell/metabolism , Fluorescent Antibody Technique , Humans , In Vitro Techniques , Interleukin-1/blood , Interleukin-6/blood , Kidney Neoplasms/metabolism , Leukocytes, Mononuclear/metabolism , Recombinant Proteins/therapeutic use , Retrospective Studies , Tumor Necrosis Factor-alpha/analysis
13.
Cancer Res ; 52(3): 726-33, 1992 Feb 01.
Article in English | MEDLINE | ID: mdl-1732060

ABSTRACT

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.


Subject(s)
Interleukin-2/therapeutic use , Killer Cells, Lymphokine-Activated/immunology , Urinary Bladder Neoplasms/therapy , Adult , Aged , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Biopsy , Drug Administration Schedule , Female , HLA-DR Antigens/analysis , Humans , Immunotherapy/adverse effects , Interleukin-2/administration & dosage , Interleukin-2/toxicity , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Metastasis , Receptors, Very Late Antigen/analysis , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Recombinant Proteins/toxicity , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathology
15.
Cancer Immunol Immunother ; 34(2): 111-4, 1991.
Article in English | MEDLINE | ID: mdl-1760814

ABSTRACT

The purpose of this study was to determine immunological parameters in the peripheral blood that correlate with the clinical effect of interleukin-2 (IL-2) in patients with metastatic renal cell cancer. A group of 26 patients with metastatic renal cell cancer underwent IL-2 treatment using a 36-day schedule with continuous intravenous IL-2 infusion (3 x 10(6) units m-2 day-1) administered from days 1 to 5 and days 12 to 16. The white blood cell count and the absolute and relative number of neutrophils, lymphocytes, eosinophils and monocytes were recorded six times in peripheral blood during the treatment. Also the blood counts of T cell and NK cell subsets and cells expressing the T cell activation markers IL-2R alpha and VLA-1 were measured. The lymphokine-activated killer (LAK) cell cytotoxicity was measured either with or without additional in vitro stimulation by IL-2. Multivariate statistical analysis showed that the clinical responses were related to the administered dose of IL-2, to a low number of blood cells expressing IL-2 receptors and to a reduction in the blood monocyte count (P less than 0.05).


Subject(s)
Carcinoma, Renal Cell/therapy , Interleukin-2/administration & dosage , Kidney Neoplasms/therapy , Monocytes/immunology , Receptors, Interleukin-2/analysis , T-Lymphocytes/immunology , Adult , Aged , Carcinoma, Renal Cell/immunology , Female , Humans , Kidney Neoplasms/immunology , Leukocyte Count , Male , Middle Aged , Receptors, Very Late Antigen/analysis
16.
Ugeskr Laeger ; 152(47): 3513-7, 1990 Nov 19.
Article in Danish | MEDLINE | ID: mdl-2256204

ABSTRACT

Interleukin-2 (IL-2) is produced by activated T-helper lymphocytes and stimulates both the antigen-specific and the non-specific immune defence. In vitro, IL-2 activated peripheral blood lymphocytes (LAK-cells) can lyse a broad spectrum of both NK-sensitive and NK-resistant tumour cell lines and IL-2 expanded tumour infiltrating lymphocytes (TIL) are, in certain cases, selectively able to lyse autologous tumour cells. In vivo, the mechanism behind the anti-tumour effect of IL-2 is unknown. Recombinant IL-2 has been available since 1984 and world-wide more than 3,000 patients have been treated. IL-2 has most frequently been administered in combination with either in vitro activated autologous effector cells and/or other cytokines or anti-cancer chemotherapeutic agents. The generation of autologous effector cells for patient treatment demands considerable resources and their contribution to the clinical effect is uncertain. The best responding tumour-types have been renal cell carcinoma and malignant melanoma with response rates up to 35% and 24%, respectively. IL-2 therapy is associated with considerable side-effects. The most serious are due to the development of a "capillary leak syndrome" with peripheral vasodilation and increased vascular permeability resulting in hypotension, oedema and organ-dysfunction. The majority of these side-effects are reversible with improvement within hours after terminating the IL-2 administration. It is concluded that IL-2 therapy is still experimental and it should be limited to treatment according to protocols in highly specialized clinical departments in a close cooperation with immunological laboratories.


Subject(s)
Immunotherapy , Interleukin-2/therapeutic use , Neoplasms/therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytokines/therapeutic use , Humans , Interleukin-2/adverse effects , Interleukin-2/genetics , Neoplasms/immunology
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