Interferon-alpha In Patients Research Articles

Внутритканевая терапия интерфероном влечении длительно незаживающих ран

The aim of the study was to improve the results of treatment of long-term non-healing postoperative wounds by intra-tissue application of alpha interferon in patients with melanoma. Material and methods of research. For the treatment of long-term non - healing wounds of patients with melanoma (T1 - 2N0M0), a solution of alpha interferon was introduced into the bottom and along the edges of the wound (the main group-37 people), and in the control (n=35), traditional wound treatment was continued. clinical and cytological parameters of the wound process were evaluated. results. The marked differences in the terms of wound cleansing and granulation appearance are shown - a decrease of 3 and 2 times, respectively, in comparison with the control group. In the main group, the time of final wound healing is 2.5 times lower than in the control group. On the 3rd day in the main group cytologically revealed a pattern of marked decrease in the inflammatory process. After 10 days after the start of alpha-interferon, there was a positive dynamics of the wound process (a decrease in the number of leukocytes and lymphocytes and an increase in connective tissue cells and macrophages). On the 14th day after the start of treatment in the main group cytological picture reflects the activation of reparative processes. In a cytological study in the control group, the above changes occur at a later date, which corresponds to the clinical picture of the course of the wound process. Conclusions. The interstitial application of interferon for the treatment of long-termnon-healin gpost operative wounds of patients with skin melanoma cansignificantly shorten the healing time of the postoperative wound by stimulatingloca limmuneresponses, followed by the development of active granulations and rapid epithelization of the wound

Radio Frequency Ablation of Renal Tumors in Patients With Metastatic Renal Cell Carcinoma

We retrospectively evaluated the feasibility, safety and outcomes of radio frequency ablation of primary renal tumors to control local disease while preserving renal parenchyma in a series of patients with metastatic renal cell carcinoma in a single institutional, multidisciplinary setting. We evaluated the records of patients with metastatic renal cell carcinoma who underwent percutaneous radio frequency ablation of a primary renal tumor. Patient demographic and disease characteristics, adjunctive medical and surgical therapies, recurrence and clinical outcomes were studied. A total of 15 patients treated between 2002 and 2008 met study inclusion criteria. There was no incomplete ablation or local recurrence. Ten patients had biopsy proven renal cell carcinoma in the ablated renal mass. Eight patients had a solitary metastasis, 3 had metastasis at 2 sites and 4 had 3 or more metastatic sites. Four patients experienced major complications. Median radiographic and clinical followup in patients at risk for an event was 25.5 and 33.0 months, respectively. The overall survival rate 1, 3 and 5 years after radio frequency ablation was 73.3%, 57.1% and 38.1%, respectively. At last evaluation 4 patients were in complete remission, 4 had no evidence of local recurrence but had evidence of distant disease and 7 had died of the disease. Radio frequency ablation is feasible and safe in highly selected patients with metastatic renal cell carcinoma, resulting in durable local control as part of multimodality management and achieving renal preservation. Further investigation is required to define the role of radio frequency ablation in this patient population.

The MRC Randomised-controlled Trial of Interferon-α, Interleukin-2 and 5-Fluorouracil vs Interferon-α Alone in Patients with Advanced Renal cell Carcinoma (RE04): Rationale and Progress

Renal cell carcinoma is diagnosed in over 6000 people, and accounts for about 2% of malignant disease annually in the UK [1]. For early stage disease, surgery with curative intent is the treatment of choice, although 30–40% of patients diagnosed with disease, apparently limited to the kidney, subsequently will relapse systemically [2]. A further 25% of patients have metastatic disease at presentation. The prognosis for metastatic renal-cell carcinoma is poor, with a median survival of 6–8 months [3]. Response rates to combination chemotherapy [4] and hormonal agents [5] have been around 5–10%. It has been known for some time that the immune system has a role in the natural history of renal-cell carcinoma. For example, spontaneous regressions are rare but well documented [6,7]. Immunotherapy with interferon (IFN) in metastatic disease produces response rates of around 10–20%, with median response durations of 3–16 months [8]. Retrospective data have also shown that patients with a performance status of 0 or 1 are more likely to gain benefit (i.e. increase in median survival) from immunotherapy than are patients with a performance status of 2 or worse [9]. Randomisedcontrolled trials have shown a survival advantage to IFN compared with non-immunotherapy. A randomised trial comparing IFN-a plus vinblastine (VLB) with VLB alone reported a median survival of about 16 months for the 79 patients receiving IFN plus VLB, and 9 months for the 81 patients treated with VLB (PZ 0.0049). Overall response rates were 16.5% for patients treated with IFN plus VLB and 2.5% for patients treated with VLB alone (PZ 0.0025) [10]. The

Combination therapy with beta and alpha interferon in patients with interferon-resistant chronic hepatitis C: Hiroshi Watanabe, Shotaro Sakisaka, Fukuoka University School of Medicine, Fukuoka Japan

Combination therapy with beta and alpha interferon in patients with interferon-resistant chronic hepatitis C: Hiroshi Watanabe, Shotaro Sakisaka, Fukuoka University School of Medicine, Fukuoka Japan

Combination therapy with beta and alpha interferon in patients with interferon-resistant chronic hepatitis C: Fukuoka Japan; Hiroshi Watanabe, Shotaro Sakisaka

Combination therapy with beta and alpha interferon in patients with interferon-resistant chronic hepatitis C: Fukuoka Japan; Hiroshi Watanabe, Shotaro Sakisaka

Lack of a strong association between HLA class II, tumour necrosis factor and transporter associated with antigen processing gene polymorphisms and virological response to α‐interferon treatment in patients with chronic hepatitis C

The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response to alpha-interferon in patients with chronic hepatitis C. Twenty-seven sustained responders and 55 non-responders to alpha-interferon monotherapy were investigated. HLA-DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR-based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (Pc). Viral genotype 1b was more frequent in responders than in non-responders (56% vs. 26%, P = 0.009). HLA-DQB1*02 occurred less frequently in responders than in non-responders (14.8% vs. 29%, Pc not significant). HLA-DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non-responders, respectively (Pc not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty-four (88.8%) responder patients as compared with 34 (61.8%) non-responders were TAP1*0101 homozygous (Pc not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment.

Ophthalmopathy due to treatment with pegylated alpha interferon in patients with chronic hepatitis C

Ophthalmopathy due to treatment with pegylated alpha interferon in patients with chronic hepatitis C

Protracted venous infusion 5-fluorouracil in combination with subcutaneous interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer: a phase II study.

Our purpose was to assess the activity of alpha-interferon (IFN-alpha), interleukin-2 (IL-2) and 5 fluorouracil (5FU) administered by protracted venous infusion (PVI) as opposed to bolus injection. 55 patients with advanced renal cell cancer were treated as follows: IL-2 and IFN-alpha according to the schedule originally described by Atzpodien, with PVI 5FU 200 mg m −2 day −1 during weeks 5–9. 42 patients (76%) were of moderate or poor prognosis as defined by previous studies. The response rate by intention to treat was 31% (17 of 55, three complete response, 14 partial response; 95% CI = 19–45%) and in evaluable patients (completed one cycle, n = 42), it was 40% (95% CI=26–57%). In addition, 24% (13 of 55) patients achieved disease stabilization. The overall median survival was 11 months with a 1-year survival of 45%. The median survival for evaluable patients was 18 months with 1- and 2-year survivals of 60% and 40% respectively. The median survival of responding patients was 31 months and the three patients achieving complete response remain progression-free at 14+, 18+ and 23+ months. Evaluable patients with poor prognostic features achieved a response rate of 54% and median survival of 18 months. Toxicity was significant yet manageable with 12 patients unable to complete one cycle due to side-effects and 36% experiencing grade 3–4 toxicities. The three on-treatment deaths were considered unlikely to be due to toxicity. The schedule of IFN-alpha, IL-2 and PVI 5FU has significant activity in advanced renal cell cancer with manageable toxicity. It is of particular interest that this regimen appears to have high activity in fit patients with poor prognostic features. Commentary Commentary on the first four abstracts appears after the fourth abstract.

Combination treatment of Sandostatin LAR with human recombinant alpha interferon in patients with metastatic neuroendocrine tumors (NET)

Neuroendocrine tumours (NET) of the appendix are rare histopathological neoplasms detected following operation for appendicitis in childhood. The role (if any) for radical surgery notably right hemicolectomy (RHC) has often reflected the ‘expert opinion’ of adult general surgeons with wider experience of managing NET lesions of the gastrointestinal tract. Critical decisions have focused on (a) tumour size, (b) histology, (c) tumour location/invasion and (d) positive lymph nodes. Against this background we report the clinical outcome of children with ‘incidental’ appendix carcinoid tumours managed at two regional UK paediatric surgery centres. A critical review of the literature is additionally provided in an effort to define contemporary patterns of care in paediatric surgical practice.Hospital records and pathology database(s) identified 27 patients at two UK centres with a confirmed histological diagnosis of appendix NET lesions during January 1997–January 2013. A PUBMED and EMBASE search strategy—(English language publications only), 1975–present, was performed to gather information on all patients younger than 20 years at primary diagnosis with NET appendix tumours to review their management and outcomes.All 27 patients treated at the two institutions had acute appendicitis including 3 cases presenting with an appendix mass. Twenty-five underwent appendicectomy with two having interval operations. Tumours had a maximum diameter of 2–18 mm (median 9 mm) with 73% of lesions located at the appendix tip. Fourteen (52%) had tumour invading the mesoappendix. All patients underwent appendicectomy only with no single case having RHC or additional surgery. Surveillance studies (5HIAA, chromogranin-A) and imaging including ultrasound or CT were deployed in a minority of patients revealing no abnormality. All 27 cases are alive and well—(mean follow up 5 years; range: 9 months–16 years). The literature highlights varied management strategies and no recorded fatalities with radical surgery in children largely evolving from adult surgical practice.This study confirms that paediatric patients with ‘incidental’ NET tumours of the appendix have an excellent prognosis. Consensus guidelines should ideally be developed by paediatric oncology surgeons to avoid unnecessary radical surgery in many otherwise healthy children.

LACK OF RETROPERITONEAL LYMPHADENOPATHY PREDICTS SURVIVAL OF PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life. A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed. Preoperative computerized tomography or magnetic resonance imaging, or radiological reports if no scans were available, were used to obtain an estimate of the volume of retroperitoneal lymphadenopathy. Operative notes were used to evaluate whether all lymphadenopathy was resected or disease left in situ, or if any extrarenal resection, including venacavotomy, was performed. Mean survival rate was calculated from the time of nephrectomy to the time of death or last clinical followup. If patients received IL-2 therapy, the response to treatment was recorded. Mean survival and response rate for IL-2 were compared among patients in 3 separate analyses. Patients without preoperatively detected lymphadenopathy were compared with those with at least 1 cm.3 retroperitoneal lymphadenopathy. Also, the patients who had detectable lymphadenopathy were divided into subgroups consisting of all resected, incompletely resected, unresectable and unknown if all disease was resected. Each subgroup was compared with patients without detectable preoperative lymphadenopathy. Patients with less than were compared to those with greater than 50 cm.3 retroperitoneal lymphadenopathy. Patients undergoing extrarenal resection at nephrectomy (complex surgery) due to direct invasion of the tumor into another intra-abdominal organ were compared with those undergoing radical nephrectomy alone, regardless of lymph node status. Statistical analysis was done with the Mantel-Cox test for comparison of survival on Kaplan-Meier curves and with Fisher's exact test for response rates for IL-2. A total of 154 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy as preparation for IL-2 based regimens. There were 82 patients with metastatic renal cell carcinoma and no preoperative retroperitoneal lymphadenopathy who survived longer (median 14.7 months) than the 72 with lymphadenopathy (median 8.5, p = 0.0004). Patients with incompletely resected, unresectable or an unknown volume resected had decreased survival compared to those with no retroperitoneal lymphadenopathy. A multivariate analysis of survival was performed evaluating the known prognostic indicators, performance status and tumor burden, as represented by the number of organs involved with metastases, and the new prognostic factor, lymphadenopathy. Lymphadenopathy was more closely associated with survival than performance status, and appeared to be a new prognostic variable. Patients with and without retroperitoneal lymphadenopathy at initial presentation had similar rates for treatment with IL-2 (54% for both groups). Of the 82 patients with no lymphadenopathy 11 (13%) had long-term survival greater than 5 years. Of the 6 complete responses to IL-2, 5 occurred in this group. Only 1 other patient with incompletely resected retroperitoneal lymphadenopathy survived longer than 5 years. No significant difference in survival was seen between patients who did or did not undergo complex surgery. Patients who presented with metastatic renal cancer and retroperitoneal lymphadenopathy had a shorter survival than those with no detectable retroperitoneal lymphadenopathy. It is warranted to continue to perform complex extrarenal resection during nephrectomy since no significant difference in the response rate for IL-2 or mean survival compared with those of patients undergoing nephrectomy alone is currently detectable.

Efficacy of treatment with lamivudine vs. Lamivudine + alpha interferon in patients with chronic active E-minus variant hepatitis B virus infection

Efficacy of treatment with lamivudine vs. Lamivudine + alpha interferon in patients with chronic active E-minus variant hepatitis B virus infection

Efficacy of treatment with lamivudine vs. lamivudine + alpha interferon in patients with chronic active E-minus variant hepatitis B virus infection

Efficacy of treatment with lamivudine vs. lamivudine + alpha interferon in patients with chronic active E-minus variant hepatitis B virus infection

Octreotide monotherapy versus combination therapy with octreotide and alpha-interferon in patients with metastatic neuroendocrine gastroenteropancreatic (GEP) carcinoma

Octreotide monotherapy versus combination therapy with octreotide and alpha-interferon in patients with metastatic neuroendocrine gastroenteropancreatic (GEP) carcinoma

Octreotide monotherapy versus combination therapy with octreotide and alpha-interferon in patients with metastatic neuroendocrine gastroenteropancreatic (GEP) carcinoma

Octreotide monotherapy versus combination therapy with octreotide and alpha-interferon in patients with metastatic neuroendocrine gastroenteropancreatic (GEP) carcinoma

A feasibility study of roquinimex (Linomide) and alpha interferon in patients with advanced malignant melanoma or renal carcinoma

Thirty-one patients with advanced renal carcinoma or malignant melanoma were treated in the first feasibility study of alpha-interferon (Roferon) and the new oral immunomodulating agent, Linomide. Linomide 5 mg or 10 mg p.o. daily was given for 2 weeks; alpha-interferon was then added at 3 MU s.c. three times weekly, escalating in each patient by 3 MU per week, if tolerable, up to 12 MJ. The combination was poorly tolerated with nausea, vomiting, somnolence and myalgia commonly reported. Adverse events accounted for treatment withdrawal in ten patients and contributed to withdrawal in four other patients. Treatment with Linomide alone in the first 2 weeks led to a significant increase in white blood cells, neutrophils and platelets. When alpha-interferon was added, the platelet count decreased significantly over the following 6 weeks. Nineteen patients had white cell phenotype and function measured. After 2 weeks of 5 mg Linomide, a transient but significant decrease in the absolute number of activated T-helper cells (CD4+DR+) was observed. No changes in natural killer (NK) cell number or activity were observed. Twenty-two patients were evaluable for response. One with metastatic renal cell carcinoma had a complete response and six had stable disease. This study does not support the use of the combination because significant toxicity was seen without the anticipated immunological benefits.

Association of HLA phenotype and response to interferon-alpha in patients with chronic myelogenous leukemia

Twenty to 25% of patients with chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-A) achieve a complete cytogenetic response (CCR). However, cells bearing rearrangement of BCR/ABL can still be detected many years after achieving a CCR despite the absence of clinical evidence of active disease. It has been suggested that the disease is kept in a dormant state by immune mechanisms. How this is achieved is not known, but it has been speculated that p210BCR/ABL might be presented by malignant cells through HLA molecules, thus making them the target for specific immune cell killing. Because specific peptides will be expressed in association with certain HLA molecules, different HLA phenotypes could be associated with different response rates to IFN-A. The response to IFN-A-based therapies in 239 patients with chronic phase CML was analyzed according to their HLA phenotype. One hundred and ninety-four (81%) achieved complete hematologic response, 142 (59%) had a cytogenetic response which was major (MCR) in 93 patients (39%): complete (CCR) in 71 (30%) and partial (PCR) in 22 (9%). Patients with an HLA-B27 phenotype had the best response rate to IFN-A: 10 of 14 (71%) had an MCR, including eight (57%) with a CCR (P=0.02). Patients with HLA-B35, -A3, and -A31 also showed a trend towards a higher response rate, whereas patients with HLA-B18 had the lowest response rate (MCR 17%). Patients with HLA-B27 and those with HLA-A31 showed a trend for better survival, whereas patients with HLA-A2, -B7, or -B18 had a trend for shorter survival. We conclude that response to IFN-A in patients with CML may be associated with the HLA phenotype. However, a much larger population would be required to determine if the impact of HLA phenotype on survival is independent of other clinical prognostic features. These findings could be relevant for the understanding of immune mechanisms of control of CML and possibly the design of immune therapy for this disease.

Ribavirin and alpha-interferon in patients with chronic hepatitis C not responding to interferon alone

Ribavirin and alpha-interferon in patients with chronic hepatitis C not responding to interferon alone

Impaired response to alpha interferon in patients with an inapparent hepatitis B and hepatitis C virus coinfection.

The possibility of hepatitis B virus (HBV) infection in HBsAg-negative patients has been shown. However, an "inapparent" coinfection by HBV in hepatitis C virus (HCV)-positive patients generally is not taken into account in clinical practice. Mechanisms responsible for resistance to interferon (IFN) have not been completely clarified. The aim of this study was to investigate whether an "inapparent" coinfection by HBV in anti-HCV-positive chronic liver disease patients may influence IFN response. Fourteen anti-HCV positive, HBsAg-negative but serum HBV DNA-positive patients by PCR and 111 anti-HCV-positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis were treated with 3 MU of recombinant alpha-2a IFN 3 times weekly for 12 months. Serum HBV DNA and HCV RNA were determined before treatment, after 6-12 months and in coincidence with ALT flare-up by PCR. HBV PCR was performed using primers specific for the S region of the HBV genome and HCV PCR with primers localised in the 5'NC region of HCV genome. IgM anti-HBc was tested using IMx Core-M Abbott assay. By the end of treatment, ALT values had become normal in 4/14 HBV DNA-positive patients (28%), but all "responders" (4/4) relapsed between 2 and 5 months after therapy. All but one patient were HCV RNA-positive before treatment, 6 were also both HBV DNA and HCV RNA-positive during ALT flare-ups. In 5 patients, only HBV DNA and in 3 patients, only HCV RNA was detected when transaminase values increased. All patients remained HBsAg-negative and anti-HCV-positive. IgM anti-HBc was detected both before treatment and during ALT elevation in 3 patients and only during ALT relapse in 3 others. Of the 111 anti-HCV positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis, a biochemical response to IFN treatment was observed in 54% of the cases. Relapse of ALT values was observed in 47% of the cases during a follow-up of 1 year after treatment. "Inapparent" HBV/HCV coinfection may be implicated in cases of resistance to IFN treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by IFN treatment. The pathogenic role of HBV in liver disease was confirmed by detection of IgM anti-HBc in some cases; the appearance of these antibodies only after IFN treatment suggests that IFN may exert a selective role in favour of HBV. Further studies will show the effect of different treatment schedules. HBV DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding interviral relationships and mechanisms involved in multiple hepatitis virus infections.

Distribution of genotypes and response to alpha-interferon in patients with hepatitis C virus infection in Germany.

To determine the distribution of hepatitis C virus (HCV) genotypes in German isolates, nucleotide sequences of the viral nonstructural 5 (NS5) genome domains were analyzed in isolates from 107 chronically HCV-infected patients. Of these 107 patients, 46 (43.0% were infected with subtype 1a and 47 (43.9%) with subtype 1b. Six patients (5.6%) with a history of intravenous drug abuse were infected with subtype 3a. Eight patients (7.5%) who had acquired their HCV infection in Egypt carried subtype 4a. Forty-three of the 107 patients were treated with alpha-interferon. Of these 43 patients, 16 (37.2%) were infected with subtype 1a and 27 patients (62.8%) with subtype 1b. Three patients infected with HCV-subtype 1a (18.7%) and four patients infected with subtype 1b (14.8%) showed a sustained complete response after interferon therapy. The HCV genotype 1 with its subtypes 1a and 1b was the most common source of HCV infection in this group of patients. There was no significant difference in response to alpha-interferon treatment of HCV infection with the subtypes 1a or 1b.

Evaluation of efficacy and safety of thymus humoral factor-gamma 2 in the management of chronic hepatitis B

Background/Aims: We investigated the antiviral and immunomodulatory effects of a combination of treatment using thymus humoral factor-gamma 2 and alpha-interferon in patients with chronic hepatitis B in whom previous monotherapy with interferon had failed. Methods: Nine HBeAg and HBV-DNA seropositive patients removed thymus humoral factor-gamma 2 alone for 2 months, thymus humoral factor-gamma 2 plus alpha-interferon for 2 months and finally alpha-interferon alone for 2 months. Results: Treatment with thymus humoral factor-gamma 2 alone was not associated with any side effects. The interferon-induced lymphopenia was significantly less marked during the combined therapy in comparison to the previous course with interferon alone (mean reduction of lymphocyte counts 33.5±11.6% versus 56.3±16.7%, respectively, p<0.05). The combination of thymus humoral factor-gamma 2 plus interferon showed a significantly more profound inhibition of serum HBV-DNA (mean reduction from the pretreatment level 90.6±13.3%) compared to the earlier monotherapy with interferon in the same patients (mean reduction 55.5±34.7%, p<0.01). As a result of the combined thymus humoral factor-gamma 2 plus alpha-interferon regimen three out of nine patients became HBV-DNA negative and seroconverted to anti-HBe. Thymus humoral factor-gamma 2 appears to exert mainly a functional effect on T lymphocytes, as interleukin-2 production was increased in the majority of treated patients, whilst the expression of lymphocyte activation markers remained unchanged. Conclusions: These data suggest that thymus humoral factor-gamma 2 may be useful in a combined therapeutic approach in chronic HBV carriers.