Subcutaneous Interferon Alpha-2a Research Articles

Interferon Alpha-2a Treatment for Post-Uveitic Refractory Macular Edema

ABSTRACTPurpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME).Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months.Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8–24] months with a follow-up of 17[10–38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] μm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] μm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events.Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.

Adjuvant Antiangiogenic Treatment for Aggressive Giant Cell Lesions of the Jaw - a 20-Year Experience at the Massachusetts General Hospital

Giant cell lesions (GCLs) are rare non-odontogenic osteolytic lesions that affect both maxillofacial and axial/appendicular skeletal structures. Aggressive lesions have a tendency to recur after surgical enucleation. To avoid en-bloc resection, adjuvant pharmacologic therapy has been used with local operative treatment. Based on the hypothesis that maxillofacial GCLs are proliferative vascular lesions and angiogenesis dependent, a protocol of at least 6 months subcutaneous interferon alpha-2a after enucleation sparing vital structures (ie. teeth and nerves) has been used since 1999 in collaboration with a hematologist/oncologist.1 The purpose of this study was to evaluate the long-term results of this standardized treatment regimen in a homogenous cohort of patients with aggressive GCLs of the maxillofacial skeleton.

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN): Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A, Ecke M, Wöltjen HH, Jentsch H, Wieland W, Wandert T, Reitz M, German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group

We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients’ status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota’s fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al , 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P = 0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P = 0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy.

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients' status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota's fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al, 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P=0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P=0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy.

Interferon Alpha-2a for Subfoveal Neovascularization in Age-Related Macular Degeneration

Background: The current study is a prospective randomized clinical trial to determine the effect of interferon alpha-2a on eyes with subfoveal subretinal neovascularization secondary to age-related macular degeneration (AMD). Methods: Twenty eyes of 19 patients with subfoveal neovascularization secondary to AMD were prospectively evaluated. Ten eyes were randomized to subcutaneous interferon alpha-2a (3 million units/m 2 ) every other day for 8 weeks, whereas 10 eyes were randomized to observation alone as controls. Fluorescein angiography, best-corrected visual acuity tests, and macular visual field assessments were performed, and all eyes were followed for a minimum of 6 months. Results: At the 2-month follow-up visit, the interferon group manifested somewhat slower neovascular growth than controls, but the results were not statistically significant. At the 6-month follow-up visit, there was no difference in visual acuity, average macular sensitivities, or extent of neovascularization. The rate of neovascular progression was significantly related to the extent of previous macular photocoagulation in both groups. Conclusion: Though the rate of neovascular progression was slowed during the second month of interferon treatment, the effect did not persist once interferon was discontinued. No long-term benefit appeared to be present. Unfortunately, lengthening the time of administration, increasing the dosage, or increasing the frequency of administration would likely give rise to unacceptable side effects.

Interferon Alpha-2a for Subfoveal Neovascularization in Age-related Macular Degeneration

The current study is a prospective randomized clinical trial to determine the effect of interferon alpha-2a on eyes with subfoveal subretinal neovascularization secondary to age-related macular degeneration (AMD). Twenty eyes of 19 patients with subfoveal neovascularization secondary to AMD were prospectively evaluated. Ten eyes were randomized to subcutaneous interferon alpha-2a (3 million units/m2) every other day for 8 weeks, whereas 10 eyes were randomized to observation alone as controls. Fluorescein angiography, best-corrected visual acuity tests, and macular visual field assessments were performed, and all eyes were followed for a minimum of 6 months. At the 2-month follow-up visit, the interferon group manifested somewhat slower neovascular growth than controls, but the results were not statistically significant. At the 6-month follow-up visit, there was no difference in visual acuity, average macular sensitivities, or extent of neovascularization. The rate of neovascular progression was significantly related to the extent of previous macular photocoagulation in both groups. Though the rate of neovascular progression was slowed during the second month of interferon treatment, the effect did not persist once interferon was discontinued. No long-term benefit appeared to be present. Unfortunately, lengthening the time of administration, increasing the dosage, or increasing the frequency of administration would likely give rise to unacceptable side effects.

Non-specific immunity in patients with primary anogenital warts treated with interferon alpha plus cryotherapy or cryotherapy alone.

Combination treatment of primary anogenital warts with subcutaneous interferon alpha 2a plus cryotherapy was no more efficacious than cryotherapy alone. Patients with primary AG warts showed no in vitro or in vivo suppression of non-specific immunity. In patients treated with interferon plus cryotherapy non-specific cellular immunity was stimulated, both in vitro and in vivo compared with patients treated with cryotherapy alone.

Subcutaneous interferon alpha 2a combined with cryotherapy vs cryotherapy alone in the treatment of primary anogenital warts: a randomised observer blind placebo controlled study.

To compare patient tolerance and treatment efficacy of subcutaneous interferon (IFN) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital (AG) warts. Randomised placebo controlled observer blind study. Statistical analysis was by chi square and Mann Whitney U tests. 60 patients with newly diagnosed AG warts. 29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy, respectively. Clinical presence or absence of AG warts. Patients wart-free at 8 weeks were asked to re-attend at 12 weeks; those with persistent warts at 8 weeks were withdrawn from the study. At 8 weeks 60.7% (17/28 patients) of the IFN group and 67.9% (19/28 patients) of the placebo group were clinically wart-free (not significant); corresponding figures at 12 week review were 29.6% (8/27 patients) and 40% (10/25 patients) respectively (not significant). There was no difference in treatment response between males and females. Recurrence of warts at three month review, in patients cleared of warts at 8 weeks, was seen in 50% (8/16) and 37.5% (6/16) of patients in the IFN and placebo groups respectively (not significant). Multiple warts and the presence of perianal/anal canal warts, either alone or concurrent with warts on the genitalia, at first clinic attendance, were adverse prognostic indicators (p less than 0.001, and p = 0.05 respectively). Cervical human papilloma virus (HPV) infection, exophytic or subclinical, was present in 58.3% and 77.2% of females in the IFN and placebo groups respectively, at trial entry. Although these lesions were not directly treated, colposcopic resolution was seen in 12.5% of affected women, in both treatment groups, by the end of the 7 week treatment period. Systemic side effects were significantly more common in the IFN than in the placebo group, 50% versus 10.7% of patients (p less than 0.01). Severe influenza like symptoms occurred, after the first three injections only, in one patient treated with IFN; all other reported side effects were mild. Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts. The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators.

Interferon alpha‐2a in cutaneous T‐cell lymphoma

23 newly diagnosed patients affected by cutaneous T-cell lymphoma were treated with sub-cutaneous interferon alpha-2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74-yr-old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow-up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha-2a is a very effective agent in therapy of untreated cutaneous T-cell lymphoma with an overall response rate of 74%.

Subcutaneous Interferon Alpha in the Treatment of Refractory Condylomata

Fifteen patients (mean age 24, range 19-46) referred for refractory vulvar warts were treated with subcutaneous interferon alpha-2a, 3 million units 3 times a week for 3 weeks. The cumulative rate of complete response was 14% at 2 weeks, 27% at one month, and 36% at three months. The response was independent of the duration of warts. The mean number of vulvar warts was 7 (range 3 to 9) among patients with complete response, 11 (range 4-20) among patients with partial response, and 23 (range 4-35) among patients with no response. The presence of cytologic or colposcopic abnormality of the cervix also predicted poor response. Adverse effects were usually mild. One patient developed progression of warts at one month and was dropped from the study. Future studies should explore the use of interferon as an adjuvant to other treatment modalities.