Track topics on Twitter Track topics that are important to you
PURPOSE We tested the hypothesis that the combination of tremelimumab and interferon alfa-2b acting via different and possibly synergistic mechanisms would overcome tumor immune tolerance and lead to significant and durable clinical responses. PATIENTS AND METHODS We conducted a phase II study in which patients were administered tremelimumab 15 mg/kg/course (three cycles [one cycle = 4 weeks]) intravenously every 12 weeks. High-dose interferon alfa-2b (HDI) was administered concurrently, including intravenous induction at 20 MU/m(2)/d for 5 d/wk for 4 weeks followed by maintenance at 10 MU/m(2)/d subcutaneously three times a week for 8 weeks per course. From course 2 onward, HDI maintenance was administered subcutaneously. Results Thirty-seven patients with American Joint Committee on Cancer stage IV (9M1a, 6M1b, and 22M1c) were enrolled. Two patients had previously treated brain metastases. Grades 3 and 4 toxicities included neutropenia (six patients; 17%), diarrhea/colitis (four patients; 11%), liver enzyme increase (four patients; 11%), rash (four patients; 11%), fatigue (15 patients; 40%), and anxiety/depression (five patients; 14%). Response data were available for 35 patients. The best objective response rate (RR; Response Evaluation Criteria in Solid Tumors) by intention to treat was 24% (90% CI, 13% to 36%; four complete responses [CRs] and five partial responses [PRs] that lasted 6, 6, > 12, > 14, > 18, 20, > 28, 30, and > 37 months, respectively). Fourteen patients (38%) had stable disease (SD) that lasted 1.5 to 21 months. The median progression-free survival was 6.4 months (95% CI, 3.3 to 12.1 months). The median overall survival (OS) was 21 months (95% CI, 9.5 to not reached). There was a weak association between therapy-induced autoimmunity and clinical benefits (CR/PR/SD; P = .0059), baseline C-reactive protein (CRP) less than or equal to 2.7× the upper limit of normal and clinical benefits (P = .0494) and improved probability of survival (P = .0032), and baseline lymphocyte count of at least 1,000/μL and response (CR/PR; P = .0183) and clinical benefits (CR/PR/SD; P = .0255). Biomarker associations were not significant after adjustment for multiple comparisons. CONCLUSION HDI can be administered combined with tremelimumab with acceptable toxicity and promising durable antitumor efficacy that warrant further testing in a randomized trial.
University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center Cancer Pavilion, 5150 Centre Ave, Fifth Fl, Pittsburgh, PA 15232; firstname.lastname@example.org.
This article was published in the following journal.
Name: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Beroctocog alfa is a second generation recombinant factor VIII manufactured by removing the B-domain from factor VIII. This prospective clinical trial was conducted to evaluate the efficacy, safety, a...
Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a...
Allergen immunotherapy for the treatment of food allergy has been a subject of intensive study within the last 10 years. After an unsuccessful attempt with subcutaneous immunotherapy for peanut aller...
No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C (CHC). This prospective, multi-center, long-t...
At present, for adults with chronic hepatitis B virus (HBV) infection, two new analogues, entecavir (ETV) and tenofovir, are recommended as the first-line therapy by the EASL (European Association for...
This study will evaluate the safety and efficacy of alb-interferon in adults with genotype 2 or 3 chronic hepatitis
Interferon alfa is an effective treatment of polycythemia vera (PV), but about 20% of patients discontinue their treatment because of side effects and treatment schedule (three times per w...
A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3
To determine the safety and efficacy of two doses of interferon alfa-2a ( IFN alfa-2a ) in combination with zidovudine ( AZT )/zalcitabine ( ddC ) versus AZT/ddC only in patients with HIV ...
The purpose of this study is to see which of two doses of PEG (polyethylene glycol) interferon alfa-2b in combination with Ribavirin for 48 weeks is more effective at elimination of hepati...
Combination Therapy With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After Therapy With Pegylated Interferon and Ribavirin
To evaluate the efficacy of pegylated interferon alfa-2a 40 kD (PEGASYS) combination therapy with ribavirin (Copegus)given for 24 or 48 weeks in patients with chronic hepatitis C (CHC) vir...
A recombinant alfa interferon consisting of 165 amino acids with arginine at positions 23 and 34. It is used extensively as an antiviral and antineoplastic agent.
A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent.
A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent.
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
Monocytes made cytotoxic by IN VITRO incubation with CYTOKINES, especially INTERFERON-GAMMA. The cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
Melanoma is a highly malignant tumor of melanin-forming cells (melanocytes) There are most commonly found in the skin (resulting from sunlight exposure), but also in the eyes and mucous membranes. Metastasis to other regions of the body is also common....
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...