Interferon Alpha-2b In Patients Research Articles

Pegylated Interferon Alpha-2b in Patients With Polycythemia Vera and Essential Thrombocythemia in the Real World.

Several clinical trials have shown promising efficacy of pegylated interferon (Peg-IFN) in the first- and second-line polycythemia vera (PV) and essential thrombocythemia (ET). However, the efficacy and safety of Peg-IFN in the real world have rarely been reported. Hence, we conducted a prospective, single-center, single-arm, open exploratory study, which aimed to explore the hematologic response, molecular response, safety, and tolerability of patients with PV and ET treated with Peg-IFN in the real world. This study included newly diagnosed or previously treated patients with PV and ET, aged 18 years or older, admitted to the Department of Hematology of the First Affiliated Hospital of Soochow University from November 2017 to October 2019. The results revealed that complete hematological response (CHR) was achieved in 66.7% of patients with PV and 76.2% of patients with ET, and the molecular response was obtained in 38.5% of patients with PV and 50% of patients with ET after 48 weeks of Peg-IFN treatment. Peg-IFN is safe, effective and well tolerated in most patients. In the entire cohort, 4 patients (9.1%) discontinued treatment due to drug-related toxicity. In conclusion, Peg-IFN is a promising strategy in myeloproliferative neoplasms (MPNs), and Peg-IFN alone or in combination with other drugs should be further explored to reduce treatment-related toxicity and improve tolerability.

TNF-Based Isolated Limb Perfusion Followed by Consolidation Biotherapy with Systemic Low-dose Interferon Alpha 2b in Patients with In-transit Melanoma Metastases: A Pilot Trial

Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon alpha-2b (LDI) might consolidate the therapeutic effect of ILP. A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50% of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.

PHASE III TRIAL CAPRI (ADJUVANT CHEMORADIOIMMUNOTHERAPY OF PANCREATIC ADENOCARCINOMA) VERSUS 5-FU ALONE

Carcinoma of the exocrine pancreas has an especially poor prognosis. The five-year survival for all stages is <1% with a median survival of 4-6 months. Even after surgical intervention with a curative intention the two-year survival is only 25%. We initiated in August 2004 a phase III trial where we compare chemoradioimmunotherapy (CapRI) with 5-FU plus folinic acid, i.e. the best arm of the first large European randomised ESPAC-1 trial. The chemoradioimmunotherapy protocol is based on results from a phase I/II trial from the Virginia Mason Clinic. They have recently published data of postoperative cisplatin, 5-fluorouracil, interferon alpha-2b, and external-beam radiation administered following pancreatico-duodenectomy. They have treated 43 patients with mainly stage III tumors. 84% had positive lymph nodes and 19% had positive cut margins. After a mean follow-up of 31.9 months, 67% of the patients were still alive. Actuarial overall survival for the 1-, 2-, and 5-year survival rate were 95%, 64%, and 55%, respectively. Primary objective is the overall survival in both arms. Secondary objective is to evaluate the role and the mechanism of interferon alpha 2b in patients' chemoradiation regimen, to assess the toxicity, the disease-free interval, the quality of life and to test different factors for their potential role as predictive marker. A total of 110 patients with R0 or R1 resected pancreatic adenocarcinoma will be enrolled. Recruiting phase should be finished after 1½ years. With a follow-up of two years a total running time of approx. 3½ years should be expected. Currently, 36 patients are enrolled. The treatment scheme is quite toxic but we are able to treat the patients as outpatients. Most patients have at least one CTC grade III toxicity as leukopenia, hand-foot-syndrome, stomatitis, Fatigue-syndrome and/or hypo-calcemia. To conclude, the treatment scheme is feasible but an experienced interdisciplinary group is needed. First clinical results are expected for end of 2006.

795 ORAL Phase II trial of sorafenib (BAY 43–9006) in combination with interferon alpha 2b in patients with metastatic renal cell carcinoma

795 ORAL Phase II trial of sorafenib (BAY 43–9006) in combination with interferon alpha 2b in patients with metastatic renal cell carcinoma

Low-dose thalidomide and interferon alpha-2b in patients with metastatic melanoma: The final results of a pilot study

7571 Background Melanoma is a hypervascular tumor and angiogenesis plays a critical role in the development/progression of metastases. Since various pathways are involved in tumor angiogenesis, a combination of agents with different anti-angiogenesis activities is a reasonable approach. Methods Patients with stage IV melanoma who failed first-line treatments were treated with a combination of thalidomide [Celgene, Warren, NJ] (200 mg/day, p.o.) and interferon alpha-2b (3 MIU, 3x/week, s.c.). Patients were evaluated monthly for toxicity and every 2 months for clinical response. Stabilization or regression of metastases was the primary endpoint of the study. Overall survival (OS), progression free survival (PFS), time to progression (TTP) and toxicity were also evaluated as secondary endpoints. Results Fifteen patients were enrolled: 9 cutaneous, 6 uveal melanoma; 10 males, 5 females; median age, 56.7 years (42–70). One patient with adrenal, mediastinal and skin metastases achieved partial response (PR), 3 patients achieved stable disease (SD), and 9 patients progressed. Two patients were not evaluable due to discontinuation of treatment prior to initial evaluation for response at 2 month (neurotoxicity, n=1; withdrawal of consent, n=1). The overall response rates (PR+SD) of “intent to treat” patients and evaluable patients were 26.7% and 30.8%, respectively. TTP was 8 months for the patient with PR, and 4, 5.5 and 12 months for 3 patients with SD. With the median follow-up of 22.8 months (12–32 months), the median OS and PFS of “intent to treat” patients were 4.2 months (1–32 months) and 3.4 months (0.5–14 months), respectively. Grade 3 toxicities related to treatment included neutropenia (n=5), elevation of transaminases (n=2), and neuropathy (n=1). No treatment-related deaths were experienced. Conclusions These preliminary results suggest that combination treatment with thalidomide and interferon alpha would be an effective palliative treatment for previously treated, stage IV melanoma patients. No significant financial relationships to disclose.

Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.

Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semisynthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducted a pilot study of Peg-IFN2b in patients with ET. Patients with a history of persistent (greater than 2 months) platelet counts >600 x 10(9)/l, with hyperplasia of bone marrow megakaryocytes in the absence of an alternate identifiable cause of thrombocytosis were eligible. Patients were required to have either thrombohemorrhagic signs and/or symptoms if previously untreated; persistence of thrombohemorrhagic signs and/or symptoms if receiving anagrelide, IFN-alpha, or hydroxyurea; or intolerance to anagrelide, IFN-alpha, or hydroxyurea. The initial PEG-IFN2b dose was from 1.5 to 4.5 micro g/kg per week subcutaneously with subsequent dose adjustments as indicated by response and adverse events. Eleven patients (nine female, median age 54 years, range 26-69 years) were treated. PEG-IFN2b rapidly controlled platelet counts and resolved symptoms in all patients. The median duration of PEG-IFN2b therapy on-study was 9 months (range 4-17 months). No patient had signs or symptoms of thrombosis or hemorrhage while on study. After 2 months of therapy, 10 patients (91%) were in complete remission, and 11 (100%) after 4 months. One patient discontinued therapy at 4 months because of persistent grade 3 fatigue and a second at 5 months because of anxiety and depression. PEG-IFN2b has significant activity in patients with ET. Long-term follow-up of a larger cohort of patients is needed to define its role in this disease.

Combination of radiation therapy and interferon alpha-2b in patients with advanced cervical carcinoma: a pilot study.

Carcinoma of the uterine cervix is the most frequent malignancy in women in developing countries. Based on the possible synergistic effect of the combination of interferon and radiotherapy, a clinical trial was conducted in patients with advanced cervical cancer. The objective was to evaluate the efficacy and security of such a therapeutic approach. This prospective phase II trial was done at the Instituto Nacional de Cancerología in Mexico City. The study included 17 consecutive patients with previously untreated squamous cell cervical cancer, clinical stages III and IV, and tumor mean size of 9.7 cm. The patients received radiotherapy and interferon alpha-2b at a dose of 5 x 106 IU/m2 3 times a week for 6 weeks. Eleven (64%) complete responses were obtained among these patients. Long-term survival was observed in 4 patients (24%) who achieved complete response and are alive after 10 years of follow-up. Immediate toxicity was mild. Late toxicity included the development of proctitis in 13 patients, colostomy was performed in 3 (23%) of them. Our results indicate that the combination of radiotherapy and this cytokine is an active therapy for squamous cell carcinoma of the uterine cervix.

Granulocyte-Macrophage Colony-Stimulating Factor and Interferon-Alpha 2B in Patients with Advanced Renal Cell Carcinoma

Objective: Biological response modifiers such as interferon-α2B (IFN-α2B) have well-known clinical activities against renal cell carcinoma (RCC). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has antitumorigenic effects both in vitro and in vivo. Therefore, a phase-I/II trial of IFN-α2B and GM-CSF was performed in patients with metastatic RCC. Methods: 21 patients in groups of 3 patients received GM-CSF at 7 different dose levels (15–300 μg) subcutaneously in combination with IFN-α2B at a fixed dose of 10 × 10⁶ IU s.c. three times weekly for 12 weeks. Results: Two complete remissions have been observed, both with lung metastases only. With increasing dose levels of GM-CSF a slight tendency to more toxicity was detectable. Due to grade-3 toxicities 5 patients (24%) dropped out of the treatment schedule. Increases in WBC, neutrophils, lymphocytes, and monocytes were noted but were not related to the dose levels of GM-CSF. Conclusions: Results demonstrate that simultaneous administration of GM-CSF and IFN-α2B is tolerated up to doses of 120–150 μg GM-CSF three times weekly. But there is no additional antitumorigenic effect of GM-CSF because the overall response rate of the combined administration of GM-CSF/IFN-α2B is similar to IFN-α2B alone and there is no obvious dose relationship between increasing doses of GM-CSF and the responses.

Toxicity and feasibility of adjuvant high dose interferon alpha-2b in patients with melanoma

Toxicity and feasibility of adjuvant high dose interferon alpha-2b in patients with melanoma

Treatment of chronic hepatitis D with interferon alpha-2b in patients with human immunodeficiency virus infection

Background/Aims: Hepatitis delta virus (HDV) coinfection is frequent in patients infected with human immunodeficiency virus (HIV), and it may cause death independently of the development of full-blown AIDS. In order to evaluate the efficacy and tolerability of interferon alpha in the treatment of hepatitis delta in HIV-infected patients, and to compare them with those observed in anti-HIV-seronegative patients,we carried out an open uncontrolled trial on 21 HIV-uninfected and 16 HIV-infected patients without severe immunodeficiency. Methods: All patients were treated with recombinant interferon alpha 2b (IFN) at doses of 10 million units thrice weekly for 6 months, and 6 million units thrice weekly for an additional 6 months. Patients showing alanine transaminase activity values persistently reduced by at least 50% from basal values received an additional 1-year course of 3 million units thrice weekly. Results: Alanine aminotransferase normalization was observed in 19% of HIV-infected and 14% of HIV-uninfected subjects during the first year; in 12% of HIV-infected and in 9% of HIV-uninfected patients during the second year. Twenty-five percent of HIV-infected and 14% of HIV-uninfected patients stopped IFN because of poor compliance or side effects. Two years after stopping interferon treatment, one anti-HIV-seropositive and two anti-HIV-seronegative patients showed complete persistent biochemical, virological and histologic remission. Conclusion: Long-term efficacy and toxicity of IFN treatment seem not to be different in HIV-infected and -uninfected patients with delta hepatitis; given the overall poor rate of long-term response, IFN treatment could be considered only in immunocompetent HIV-HDV-coinfected patients, strictly selected because of rapidly evolving liver disease.

Determination of in vitro drug sensitivity to a panel of cystostatic drugs and interferon alpha-2b in patients with renal cell carcinoma.

Fresh operative cells from 27 renal cell carcinomas (RCC) were cultured in vitro for the determination of in vitro drug sensitivity. Two samples were not culturable. Incubation was carried out in triplicate in the presence and absence of various concentrations of chemotherapeutic agents. Sensitivity of the tumour cells to interferon-alpha (IFN-alpha), cisplatin (CDDP), mitomycin C (MMC), vinblastine (VBL), doxorubicin (DOX), etoposide (ETOP), bleomycin (BLM), vincristine (VCR) were tested by a colorimetric assay using MTT. A preexposure viability over 75% was essential for in vitro drug sensitivity assay (IVDSA). Sensitivity was determined by a more than 50 +/- 2 SD% reduction from the control absorbance. All eight drugs in their low concentrations exhibited cell proliferation inhibition in 0-12% of RCCs. On the other hand, IFN-alpha in its higher concentration (60 IU/ml) was effective in 88% of RCCs. After IFN, CDDP was found to be the second most effective drug in its higher concentration (36% efficacy). The results indicate that IFN appears to be the most effective in vitro agent in our 25 RCCs and the clinical trials either as a monotherapy or multiple combinations of various agents should include IFNs for the treatment of RCC.

Bacillus calmette-Guérin plus intravesical interferon alpha-2b in patients with superficial bladder cancer

Objectives Bacillus Calmette-Guérin (BCG) and interferon alpha-2b (IFN α2b) have been used individually for the treatment of bladder cancer. We used a low dose of BCG combined with IFN α2b to determine the safety and to assess the efficacy of this combination therapy. Methods A study of 12 patients with superficial bladder cancer evaluated the safety and efficacy of a combination of low-dose BCG and IFN α2b, given weekly for 6 weeks. Three patients were assigned to each of four groups in which 60 mg of BCG was combined with 10, 30, 60, or 100 × 10 6 ILJ of IFN α2b. Results The combination BCG/IFN α2b therapy was well tolerated, with adverse effects being mild to moderate and resolved at the end of treatment. At 12 months post-treatment there has been no tumor progression. Two patients with previous multifocal transitional cell carcinoma have had solitary recurrences. One patient has had recurrent carcinoma in situ. Conclusions This preliminary study found combination BCG/IFN α2b induction therapy to be safe and well tolerated. These early results show a high response rate, but efficacy can only be determined with Phase II and III studies.

Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected] [published erratum appears in Blood 1992 Jun 15;79(12):3397

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit- erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.

Treatment With Recombinant Interferon (α-2β) Early After Bone Marrow Transplantation in Patients at High Risk for Relapse

Abstract Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit- erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.

Recombinant Interferon Alpha-2b in Patients with Progressive and/or Recurrent Hodgkin's Disease.

Six patients were included in a trial involving the SC administration of rIFN{alfa)-2b (Schering Plough) at a dose of 5 {multi} 10(6) IU daily, 5 days a week and continued while a clinical response was observed. All patients had previously received between 3 to 5 salvage chemotherapy programs without a disease free interval prior to the administration of rIFN{ALFA}-2b. Two patients had extranodal disease (lung, bone) and all 6 patients had "B" symptoms. Five of the patients showed stable disease, for a period of 3 to 12 months. One patient with recurrent HD obtained partial remission which lasted 26 months, at which time he developed autoimmune hemolytic anemia. Toxicities observed were mild and consisted of a flulike syndrome, supraventricular tachycardia and mild increase in transaminases. The quality of life improved while on rIFN{ALFA}-2b therapy, contrasting with the toxicity of the aggressive chemotherapy regimens previously administered which required frequent hospitalizations. This preliminary experience suggests that the role of rIFN{ALFA}-2b in the treatment of HD requires more study.