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Prospective study of clinical characteristics of melanoma patients with retinopathy caused by a high-dose interferon α-2b.

ABSTRACT: Retinopathy is a rare side effect of interferon α-2b treatment. The goal of this study was to prospectively investigate the clinical characteristics of Chinese patients with melanomas who developed retinopathy following high doses of interferon α-2b (HD-IFN) therapy. The study included 56 melanoma stage I-III patients that were treated with HD-IFN. Fourty-three patients developed HD-IFN-induced retinopathies. Forty-three melanoma patients (76%) developed retinopathy after being treated with HD-IFN. Among these patients, 49% had cotton-wool spots, 19% had retinal hemorrhage, and 30% had retinal hemorrhage. The median time of occurrence of retinopathy was 4 weeks after treatment, and the median time of duration was 4 weeks. No patient showed other symptoms except one who had blurred vision. A comparison of clinical characteristics (age, gender, primary site, stage, and ulceration) and laboratory examinations (white blood cell and platelet counts, hemoglobin, serum lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, triiodothyronine, thyroxine, thyroid-stimulating hormone, and lipid) between the HD-IFN-induced retinopathy patients and nonretinopathy patients did not show any significant differences (P > 0.05). Although all patients that developed retinopathy had diabetes or hypertension, an equal percentage of patients were without retinopathy had diabetes or hypertension. HD-IFN therapy in patients with melanomas may induce mild retinopathy. Our results; however, do not necessarily suggest to discontinue the HD-IFN treatment because retinopathy is a reversible disorder.

SUBMITTER: Lan S

PROVIDER: S-EPMC8568323 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma.

Project description: Not available

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Evaluation of interferon alpha 2b as adjunctive therapy for conjunctival melanoma.

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| S-EPMC6543011 | biostudies-literature

Neoadjuvant Pembrolizumab and High-Dose IFNα-2b in Resectable Regionally Advanced Melanoma.

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| S-EPMC8338751 | biostudies-literature

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| S-EPMC3043235 | biostudies-literature

Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

Project description:In the adjuvant setting for malignant melanoma, interferon (IFN)-?-2b and pegylated (PEG) IFN-?-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-?-2b. As with a previously reported phase III study, patients were to receive PEG IFN-?-2b 6 ?g/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 ?g/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-?-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial.

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Project description:This research aimed to find out the impact of ionizing radiations on the hIFNα-2b gene of radiotherapy treated cancer patients. The gene hIFNα-2b synthesizes a protein which is an important anticancerous and antiviral protein. The cancer patients (breast, lung, thyroid, oral and prostate) who were undergoing a radiotherapy treatment were selected. A molecular analysis was performed for DNA isolation and gene amplification through PCR, to identify gene mutations. Further, by bioinformatics tools we concluded that how mutations identified in gene sequences have led to the alterations in the hINFα-2b protein in radiotherapy receiving cancer patients. The 32% mutations in the hINFα-2b gene were identified and all were frameshift mutations. Radiotherapy can impact the immune system and cancer patients may modulate their immunity. Understaning the mechanisms of radiotherapy-elicited immune response may be helpful in the development of those therapeutic interventions that can enhance the efficacy of radiotherapy.

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A phase I trial of bortezomib and interferon-?-2b in metastatic melanoma.

Project description:The possibility that cytokine administration could enhance the antitumor effects of proteasome inhibition was explored. It was found that coadministration of bortezomib and interferon-? (IFN-?) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. A phase I study was conducted to determine the tolerability and the maximum tolerated dose of bortezomib when administered in combination with IFN-?-2b to patients with metastatic melanoma. Patients were treated on a 5-week cycle. In week 1 of cycle 1, patients received 5 million U/m(2) IFN-? subcutaneously thrice weekly. During weeks 2-4 of cycle 1, bortezomib was administered intravenously weekly along with IFN-? thrice weekly. There was a treatment break during week 5. After cycle 1, bortezomib was administered in combination with IFN-?. Bortezomib was administered in escalating doses (1.0, 1.3, or 1.6 mg/m) to cohorts of 3 patients. Sixteen patients were treated (8 women, 8 men; median age 59 y). Common grade 3 toxicities included fatigue (5), vomiting (3), and diarrhea (3). Grade 4 toxicities included fatigue (3) and lymphopenia (1). The maximum tolerated dose for bortezomib was 1.3 mg/m(2). One patient had a partial response, and 7 had stable disease. Progression-free survival was 2.5 months, and overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-? to induce phosphorylation of STAT1 in circulating immune cells; however, it did lead to reduced plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-? can be safely administered to melanoma patients.

| S-EPMC4174542 | biostudies-literature

Cost-effectiveness of ipilimumab versus high-dose interferon as an adjuvant therapy in resected high-risk melanoma.

Project description:BackgroundAdjuvant ipilimumab was found to improve the overall survival and reduce toxicity compared to high-dose interferon (HDI) in patients with resected, high-risk melanoma. However, the cost of ipilimumab is substantially higher than HDI. This study evaluates the cost-effectiveness of ipilimumab as an adjuvant treatment in melanoma from a healthcare perspective.MethodsWe designed a Markov model simulating resected, high-risk melanoma patients receiving either ipilimumab or HDI. Transition probabilities, including risks of survival, disease progression, and toxicity, were ascertained from clinical trial data. Costs and quality of life measurements (health utilities) were extracted from the literature. Incremental cost-effectiveness ratios (ICERs), defined as incremental costs divided by incremental quality-adjusted life-years (QALYs), assessed cost-effectiveness. ICERs <$100,000/QALY were deemed cost-effective. We measured model uncertainty with one-way and probabilistic sensitivity analyses.ResultsIn our base case model, ipilimumab increased costs by $107,100 and increased effectiveness by 0.43 QALY, yielding an ICER of $392,600/QALY. Our model was moderately sensitive to the costs of ipilimumab, though the cost of ipilimumab would need to decrease by 44% for ipilimumab to become cost-effective compared to HDI. The model was not sensitive to survival, toxicity, or other costs. Probabilistic sensitivity analysis showed that HDI would remain the cost-effective treatment option 96.2% of the time at a willingness-to-pay threshold of $100,000/QALY.ConclusionsAdjuvant ipilimumab increases the survival and decreases the toxicity compared to HDI in resected, high-risk melanoma patients, though this would not be considered cost-effective due to the high price of ipilimumab.

| S-EPMC8495287 | biostudies-literature

Heterologous expression, immunochemical and computational analysis of recombinant human interferon alpha 2b.

Project description:Interferon alpha 2b (IFN?-2b) is an important cytokine and used for antiviral and anticancer treatment. The low cost production of IFN?-2b with high biological activity is necessary to provide the interferon therapy to the hepatitis patients in Pakistan. In the present study, human interferon alpha 2b (hIFN?-2b) gene from a healthy person was cloned and overexpressed in E. coli BL21(DE3). The molecular weight of the expressed hIFN?-2b is 19 kDa. The over expressed recombinant hIFN?-2b was checked by ELISA using antibodies raised against commercially available hIFN?-2b. The biocomputational analysis of recombinant hIFN?-2b gene showed the 99.9% nucleotide sequence and 100% deduced amino acid sequence homology with reported sequences of IFN?-2b. The predicted 3D-structure showed mainly five ?-helices, one 310 helix and two disulfide bonds at Cys1-Cys98 and Cys129-Cys138. The amino acid sequence alignment indicated that the disulfide linkage position is conserved in all IFN? family members. On the basis of sequence homology among interferon alpha family, new potent variants of hIFN?-2b with enhance efficacy can be produced. Indigenous production of IFN?-2b from gene of local population will reduce the cost and increase tolerability of interferon therapy.

| S-EPMC3695685 | biostudies-literature

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