Retreatment of chronic hepatitis C with interferon-alpha.
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Adult↗
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Results for “Interferon alpha-2”
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Type I interferons inhibit hepatitis B virus replication and induce hepatocellular gene expression in cultured liver cells.
A hepatoblastoma cell line transfected with hepatitis B virus (HBV) DNA (Hep G2.2.15) was used to investigate the effects of interferons (IFNs) on HBV replication and hepatocellular gene expression. IFN-alpha 2b or -beta inhibited HBV replication transiently. In parallel, there was a decrease in the amount of HBV mRNA. Hepatitis B surface antigen and early antigen secretion were not influenced; however, their intracellular levels diminished during treatment. The cellular 2',5'-oligoadenylate synthetase activity was increased 9- to 18-fold during treatment of cells with IFN-gamma, -alpha, or -beta. The number of IFN-alpha and -beta receptors was down-regulated, while the number of IFN-gamma receptors remained constant. The expression of major histocompatibility complex class I antigens was stimulated by addition of IFN-alpha or -beta. These data show that both IFN-alpha and -beta can effectively inhibit HBV replication and induce a cellular IFN response in Hep G2.2.15 cells similar to that seen in humans.
2',5'-Oligoadenylate Synthetase↗
Decreased catabolism of fluorouracil in peripheral blood mononuclear cells during combination therapy with fluorouracil, leucovorin, and interferon alpha-2a.
BACKGROUND: We previously reported that recombinant interferon alpha-2a (IFN alpha-2a) therapy was associated with a dose-dependent decrease in fluorouracil (5-FU) clearance. PURPOSE: In this study, we used peripheral blood mononuclear cells (PBMCs), which are responsive to IFNs, as surrogate tissue to determine whether the change in clearance might be explained by decrease in 5-FU catabolism during IFN alpha-2a therapy. METHODS: The study population consisted of 45 patients with adenocarcinoma arising in the gastrointestinal tract. Thirty-seven patients received therapy containing IFN alpha-2a at a median dose of 5 million U/m2 per day (range, 1.7-7.5 million U/m2 per day) starting on day 1 and continuing through either day 7 or day 14 in conjunction with intravenous high-dose leucovorin (LV) followed by bolus 5-FU on days 2-6. Eight patients received the same schedule of 5-FU and LV daily for 5 days without IFN alpha-2a but with granulocyte-macrophage colony-stimulating factor starting on day 6 and ending at least 3 days prior to the start of the next cycle. Peripheral blood was collected during 70 cycles on days 1, 2, and 4 prior to the daily treatment with IFN alpha-2a + 5-FU+LV and during 19 cycles on days 1 and 4 prior to the daily treatment with 5-FU+LV without IFN alpha-2a. In a given patient cycle, matched samples were drawn at approximately the same time of day. PBMCs were isolated, and the intact cells were exposed to 4 microM [3H]5-FU, and the formation of [3H]dihydrofluorouracil was determined by reverse-phase high-performance liquid chromatography. RESULTS: In 47 matched patient cycles from IFN alpha-2a + 5-FU+LV-treated patients in which samples were available on days 1, 2, and 4, 5-FU catabolism decreased by 20% (P2 = .03) and 41% (P2 = .0001) from the baseline catabolic rate (2.5 +/- 0.2 pmol/min per 10(6) cells [mean +/- SE]) on days 2 and 4, respectively. Using information from all paired samples, the mean change from baseline on day 2 was -0.4 +/- 0.2 pmol/min per 10(6) cells (n = 54; P2 = .05), and the change from baseline on day 4 was -1.3 +/- 0.3 pmol/min per 10(6) cells (n = 63; P2 = .0001). In contrast, changes in 5-FU catabolism were not evident in the PBMCs of the reference population receiving 5-FU+LV without IFN alpha-2a. CONCLUSIONS: The magnitude of the change in 5-FU catabolism is similar to the magnitude of the decrease in 5-FU clearance in our previous study. These observations suggest that changes in 5-FU catabolism during therapy with IFN alpha-2a, 5-FU, and LV may account for the decreased 5-FU clearance.
Adenocarcinoma↗
Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.
A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.
Adult↗
Treatment with alpha-interferon versus alpha-interferon in combination with streptozocin and doxorubicin in patients with malignant carcinoid tumors: a randomized trial.
An open randomized trial was performed to compare the effect of recombinant interferon-alpha 2a (rIFN-alpha 2a) (group A, n = 12) versus rIFN-alpha 2a in combination with chemotherapy (group B, n = 11) in patients with malignant carcinoid tumors. Both groups received rIFN-alpha 2a at a dose of 3 MU/m2 s.c. three times weekly during the first 6 months. IFN was discontinued every third week in group B, followed by an i.v. injection of 2 g streptozocin and 40 mg/m2 doxorubicin. After 6 months group A showed one complete biochemical response (CR), 9 patients with stable disease (SD) and 2 who progressed (PD). Two patients had a partial reduction (PR) of tumor size, 9 showed SD and one PD. All patients in group B demonstrated SD. Chemotherapy was withdrawn after 6 months and all patients continued with rIFN-alpha 2a at an increased dose of 3 MU/m2 five days/week for a further 6 months. After 12 months 6 patients showed PR, 12 SD and one PD biochemically. Tumor size showed SD in 18 patients and PD in one. One patient died from cardiomyopathy, probably induced by doxorubicin. Antibodies against rIFN-alpha 2a developed in 41% of the patients. In conclusion, we detected no difference in response rates between the two treatment groups. Adverse reactions from the combination were considerable. The frequent development of IFN antibodies might have interfered with the therapeutic results.
Aged↗
Alpha interferon-2a (Roferon-A) in the treatment of diffuse cutaneous systemic sclerosis: a pilot study. UK Systemic Sclerosis Study Group.
Intramuscular alpha-interferon improved or stabilized skin score in 10/14 (71%) patients with diffuse cutaneous systemic sclerosis. In 64% of patients, their treating physicians rated it as having stabilized or improved the disease. However, it had no significant effect on grip strength, digital contractures, respiratory function or visceral involvement. Type I collagen synthesis was significantly reduced in fibroblasts cultured from clinically 'uninvolved' skin but not in those from lesional skin. Amino-terminal procollagen III peptides in the interferon treated group were not significantly reduced after 6 months of therapy but showed a trend towards stabilization and reduction compared to disease matched controls on no therapy.
Adult↗
Treatment of hairy cell leukemia with granulocyte colony-stimulating factor and recombinant consensus interferon or recombinant interferon-alpha-2b.
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.
Drug Evaluation↗
Combination therapy with interferon alpha-2b plus low-dose interferon gamma in pretreated patients with Ph-positive chronic myelogenous leukaemia.
Between March 1988 and July 1990, 28 adults with chronic myelogenous leukaemia (CML) were treated with a combination of recombinant human interferon (IFN) alpha-2b s.c. (initial dose 4 x 10(6) U/m2) and recombinant human IFN gamma s.c. (50 micrograms totally) daily. All patients were in chronic phase disease and had been treated previously with chemotherapy or bone marrow transplantation. A complete haematologic remission was achieved in three patients (11%), a haematologic remission in 12 patients (43%), and a partial haematologic remission in seven patients (25%). Six patients did not respond to this schedule. Acute side-effects were flu-like symptoms, fever and chills. During long-term treatment six patients developed polyarthralgia. Haematotoxicity WHO grade III occurred in three patients, and WHO grade IV in two patients. One patient developed psychosis, and in another patient an exacerbation of a pre-existing sarcoidosis was observed. We conclude that this combination is tolerable and effective in inducing haematological remissions in pretreated CML patients.
Adolescent↗
Treatment of basal cell carcinoma with intralesional interferon alpha: a case report and literature review.
We report the case of a 76 year old man with three ulcerated basal cell carcinomas on his lower limbs. He was considered unsuitable for surgical therapy and was treated by intralesional interferon alpha-2b (Intron A) injections. Twenty months post therapy two of the three treatment sites remain clinically cured. Recurrence occurred at the site which received the smallest total dose of interferon. A review of the therapeutic trials of interferon alpha for basal cell carcinoma is presented. We conclude that interferon alpha-2b is a useful agent for treatment of basal cell carcinoma in selected patients.
Aged↗
Systemic interferon-alpha 2a and subretinal neovascular membranes.
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Choroid↗
Treatment of subfoveal choroidal neovascular membranes with systemic interferon-alpha 2a.
Systemic interferon-alpha has recently been reported to be useful in the treatment of choroidal neovascular membranes (CNVM) in age-related macular degeneration. To further investigate its effect we treated eight patients with subfoveal choroidal neovascular membranes of various aetiologies including idiopathic, age-related macular degeneration and myopic chorioretinal degeneration. Only one of the eight patients responded with an angiographically demonstrated decrease in the size of the CNVM; this was in a patient from the idiopathic group. Considerable side-effects were reported with marked lethargy and malaise limiting compliance with some patients. Although this is an initial report with limited patient numbers and follow-up, it does suggest a role for interferon-alpha in patients with idiopathic neovascular membranes where the retina is otherwise normal, but raises some doubt as to its efficacy in the treatment of age-related macular degeneration.
Adult↗
Initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome of interferon-alfa-2b therapy in chronic myelogenous leukemia.
Eleven previously untreated patients with chronic-phase Philadelphia-chromosome-positive chronic myelogenous leukemia were treated with cytotoxic chemotherapy followed by interferon-alfa-2b (IFN-alpha) maintenance. Initial chemotherapy consisted of three cycles of mitoxantrone 10 mg/m2 on day 1 and 2, and cytarabine 100 mg/m2 daily for 5 d. Complete hematological response was obtained in 9 (82%) patients with moderately associated toxicity. However, cytogenetic responses after three cycles were poor and transient (1 partial suppression and 2 minor suppression of Ph chromosome). Maintenance therapy with IFN-alpha was started in 10 patients at 5 x 10(6) U/m2 daily with dose reduction if hematologic toxicity or severe side-effects occurred. Of 9 evaluable patients treated for more than 3 months, 6 patients maintained a complete hematological response, whereas 1 patient remained in partial remission and 2 patients showed progressive disease. Cytogenetic evaluation showed partial suppression of Ph chromosome in 1 patient, whereas 1 patient had a minor response and 5 patients had no change or evolution of new chromosome abnormalities. As the results are not superior to IFN-alpha treatment alone, it is concluded that initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome of therapy in CML.
Adult↗
Multiple myeloma: intensified maintenance therapy with recombinant interferon-alpha-2b plus glucocorticoids.
Interferon-alpha-2b has been demonstrated to prolong remission duration and survival in responding multiple myeloma patients. The aim of this study was to evaluate intensification of this maintenance therapy through the addition of glucocorticoids. Eighteen myeloma patients at diagnosis received six-12 courses of conventional chemotherapy and then interferon + glucocorticoids. This treatment included 3 megaunits of interferon three times a week, plus 4 days of pulsed high-dose dexamethasone (40 mg/d for 4 d every 28 d for 6 months/year) in patients < 70 yr old, or oral prednisone (50 mg three times a wk) in patients > 70 yr old. Conventional chemotherapy induced an objective response in 13/18 patients and a further reduction of the M component (> 50%) was achieved during interferon + glucocorticoids treatment in 7/13. 4/18 patients relapsed with a median follow-up of 22 months (range 13-40). These findings indicate that interferon + glucocorticoids, after inductional chemotherapy, further reduces tumor burden and may prolong remission.
Adult↗
Three years' continuous low-dose interferon-alpha treatment of hairy-cell leukaemia: evaluation of response and maintenance dose.
Thirty-six HCL patients were treated with 2 x 10(6) U/m2 IFN-alpha-2b three times weekly for 24 months, followed by 12 months of treatment with one of three doses ranging from 0.5 x 10(6) U to 2 x 10(6) U/m2. For most patients the response continued to improve during the whole treatment period, and there were no cases of disease progression during treatment. Patients with disease of short duration before IFN treatment and/or non-splenectomized patients seemed to respond more slowly than others, but there were no differences between patients treated with the different IFN doses. Toxicity was usually WHO grade 1 or 2. The continued improvement in a large number of patients even with very small IFN doses might indicate that only a small number of true complete responses are reached after 24 months of treatment, thus explaining the reported high relapse rate after early discontinuation of treatment. It therefore seems worthwhile--also from a cost/benefit point of view--to test long-term or continuous IFN-alpha treatment at other centres.
Follow-Up Studies↗
Mechanisms accounting for the impaired natural-killer cell activity in refractory anaemia with excess of blasts.
Natural killer (NK) cells were analyzed in 38 untreated patients with refractory anaemia with excess of blasts (RAEB), using cytotoxicity assays and immunofluorescence with monoclonal antibodies. We found that patients with RAEB have normal numbers of peripheral blood and bone marrow NK cells. NK cells from RAEB patients express very low natural-killer cell activity (NKa) which may be increased significantly with recombinant alpha-interferon and recombinant interleukin-2, although it remains below the lower limit of the control range. The cells exhibit normal tumour cell binding capacity, but fail to release sufficient amounts of natural-killer cytotoxic factors (NKCFs) upon their interaction with NK-sensitive K562 cell targets or their stimulation with phytohaemagglutinin. Our results suggest that defective NKa in RAEB patients may be due, at least in part, to impaired release of functionally active NKCFs. This disturbance is probably the result of some intrinsic defect of RAEB NK cells in NKCF production, storage, and/or release. The possibility of an impairment in the activation signal provided by the stimulatory K562 cells cannot be excluded, although it seems unlikely. We postulate that this abnormality might represent a manifestation of dysplastic haemopoiesis. Further studies are certainly needed to investigate whether other defective mechanisms are also implicated in the determination of the low NKa in patients with RAEB.
Adult↗
Peripheral blood lymphocyte subsets in patients with chronic hepatitis C--effects of interferon treatment.
Thirty-three patients with chronic hepatitis non-A, non-B/C were included in a randomized controlled study of recombinant alpha-2b interferon treatment 3 MU three times weekly for 36 weeks. In lysed whole blood, lymphocyte subpopulations were enumerated by flow cytometry detecting fluorescein or phycoerytrin conjugated monoclonal antibodies directed against seven different epitopes. Patients with chronic active hepatitis were significantly older than patients with chronic persistent hepatitis (p less than 0.05). Before treatment, the proportions of different subsets of lymphocytes were within the normal reference values and the CD4/CD8 ratio was also normal. No increased activation of T-cells was noticed. Patients over 50 years of age, however, had a significantly increased (p less than 0.01) proportion of HLA-DR+ lymphocytes, mainly B-cells. Treatment decreased the absolute number of peripheral blood leukocytes and lymphocytes. There was also a significant decline in the proportion of CD8+ lymphocytes and NK-cells, and a significant increase in the proportion HLA-DR+ cells and of the CD4/CD8 ratio. The increased proportion of HLA-DR+ cells, however, did not reflect peripheral T-cell activation; instead, it was due to increasing B lymphocyte numbers.
Alanine Transaminase↗
A placebo controlled observer blind immunocytochemical and histologic study of epithelium adjacent to anogenital warts in patients treated with systemic interferon alpha in combination with cryotherapy or cryotherapy alone.
OBJECTIVE: To examine biopsy specimens of tissue immediately adjacent to anogenital (AG) warts which had been treated with either cryotherapy plus subcutaneous interferon (IFN) alpha 2a or cryotherapy alone, for histological features of (a) human papilloma virus (HPV) infection (b) localised cellular immune responses, to further characterise any cellular immune infiltrates with tissue immunocytochemistry, and to relate any histological, immunocytochemical findings to the treatment response of nearby AG warts. DESIGN: A randomised placebo controlled observer blind study. SETTING: Genitourinary Medicine clinic, Department of Immunopathology, Royal Victoria Hospital, Belfast, N. Ireland. SUBJECTS: Thirty patients with AG warts; 16 treated with IFN alpha 2a plus cryotherapy, and 14 treated with cryotherapy alone. OUTCOME MEASURES: (1) Light microscopic features associated with HPV infection and local cellular immune responses. (2) Indirect immunofluorescence detection of the following cell surface markers: HLA DR, alpha one antitrypsin, CD1, CD3, CD4, CD8, CD22. (3) Clinical response of AG warts to treatment. RESULTS: In pre-treatment biopsies only non specific indicators of HPV infection (acanthosis, 29/30 biopsies, and hyperkeratosis, 7/30 biopsies) were seen on light microscopy. Mononuclear cells were seen both throughout the upper dermis and centred around dermal blood vessels in 19/30 (63.3%) biopsies, and infiltrating into the epidermis in 12/30 (40%) biopsies. On indirect immunofluorescence CD3, CD8, CD4 antigen was detected on the surface of cells throughout the upper dermis in 24/29 (82.7%), 15/29 (51.7%), and 3/29 (10.3%), of biopsy specimens respectively. CD3 antigen, CD8 antigen and CD4 antigen was detected on the surface of cells infiltrating into the epidermis in 18/29 (62%), 7/29 (24.1%), and 6/29 (20.7%) of biopsy specimens respectively. CD1 antigen was seen on the surface of dendritic cells throughout the epidermis in all specimens; CD1 positive cells infiltrated into the upper dermis in 5/29 (17.2%). HLA DR was detected on the surface of dendritic cells throughout the epidermis in 22/29 (75.9%) of specimens, and on the surface of cells scattered both diffusely throughout the upper dermis and centred around dermal blood vessels in all specimens. Alpha one antitrypsin (A1AT) antigen was seen on the surface of cells in the upper dermis in 6/29 (20.7%) of biopsy specimens; no cells expressing CD22 surface antigen were seen. The nature of this local cellular immune response was not altered by treatment of nearby warts with either cryotherapy alone or cryotherapy plus systemic IFN alpha 2a, or related to the therapeutic outcome of these warts. CONCLUSIONS: (1) No convincing histological evidence of HPV infection was seen in epithelium surrounding AG warts. (2) A predominantly T cell-mediated immune response (the target of which is uncertain) was seen in this perilesional epithelium. (3) In the dosage regimens used in this study, treatment of AG warts with either systemic IFN alpha 2a plus cryotherapy or cryotherapy alone did not appear to augment localised cellular immune responses (against any presumed subclinical HPV infection) in epithelium surrounding AG warts.
Adolescent↗
[Combination therapy of Buschke-Löwenstein tumor with CO2 laser and interferon-alpha].
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Aged↗