Standard diametric versus volumetric early tumor shrinkage as a predictor of survival in metastatic colorectal cancer: subgroup findings of the randomized, open-label phase III trial FIRE-3 / AIO KRK-0306.

Objectives: Early tumor shrinkage (ETS) quantifies the objective response at the first assessment during systemic treatment. In metastatic colorectal cancer (mCRC), ETS gains relevance as an early available surrogate for patient survival. The aim of this study was to increase the predictive accuracy of ETS by using semi-automated volumetry instead of standard diametric measurements.

Efficacy of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in 1st-line treatment of older patients with RAS wild-type metastatic colorectal cancer: an analysis of the randomised trial FIRE-3.

Background: The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour.

Methods: The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness.

Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first-line treatment within the randomized Phase III trial FIRE-3 (AIO KRK-0306).

Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE-3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS-WT tumors (ie, wild-type in KRAS and NRAS exons 2-4).

FOLFIRI plus cetuximab or bevacizumab for advanced colorectal cancer: final survival and per-protocol analysis of FIRE-3, a randomised clinical trial.

Background: Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.

Methods: The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC.

Single-nucleotide variants, tumour mutational burden and microsatellite instability in patients with metastatic colorectal cancer: Next-generation sequencing results of the FIRE-3 trial.

Background: Molecular biomarkers and primary tumour sidedness guide treatment decisions in metastatic colorectal cancer. Comprehensive molecular profiling aims to identify targetable alterations and measure tumour mutational burden (TMB) to enable precision oncology.

Material And Methods: FoundationOne® next-generation sequencing identified single-nucleotide variants (SNVs), copy number alterations, high TMB (TMB-H) and high-grade microsatellite instability (MSI-H) in patients treated in the FIRE-3 trial.

Relevance of liver-limited disease in metastatic colorectal cancer: Subgroup findings of the FIRE-3/AIO KRK0306 trial.

In metastatic colorectal cancer (mCRC), liver-limited disease (LLD) is associated with a higher chance of metastectomy leading to long-term survival. However, limited data describes the prognostic and predictive relevance of initially unresectable LLD with regard to targeted first-line therapy. The present analysis investigated the relevance of initially unresectable LLD in mCRC patients treated with targeted therapy against either the epidermal growth factor receptor (EGFR) or vascular epithelial growth factor (VEGF).

Relation of early tumor shrinkage (ETS) observed in first-line treatment to efficacy parameters of subsequent treatment in FIRE-3 (AIOKRK0306).

We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after 6 weeks of treatment. Shrinkage was classified as ETS (shrinkage by ≥ 20%), mETS (shrinkage by 0 to <20%), mPD (minor progression >0 to <20%) and PD (progression ≥20%).

FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial.

Background: FIRE-3 compared first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in patients with KRAS exon 2 wild-type metastatic colorectal cancer. The same study also reported an exploratory analysis of a subgroup of patients with tumours that were wild-type at other RAS genes (KRAS and NRAS exons 2-4). We report here efficacy results for the FIRE-3 final RAS (KRAS/NRAS, exons 2-4) wild-type subgroup.

Impact of Subsequent Therapies on Outcome of the FIRE-3/AIO KRK0306 Trial: First-Line Therapy With FOLFIRI Plus Cetuximab or Bevacizumab in Patients With KRAS Wild-Type Tumors in Metastatic Colorectal Cancer.

Purpose: We investigated choice and efficacy of subsequent treatment, with special focus on second-line therapy, in the FIRE-3 trial (FOLFIRI plus cetuximab [arm A] or bevacizumab [arm B]) for patients with KRAS wild-type metastatic colorectal cancer.

Patients And Methods: Start of subsequent-line (second or third) therapy was defined as use of an antitumor drug that was not part of the previous regimen. We evaluated choice, duration, and efficacy of subsequent therapy and determined the impact of subsequent-line treatment on outcome of patients in FIRE-3.

FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial.

Background: Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. We aimed to compare these agents in patients with KRAS (exon 2) codon 12/13 wild-type metastatic colorectal cancer.

Methods: In this open-label, randomised, phase 3 trial, we recruited patients aged 18-75 years with stage IV, histologically confirmed colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, an estimated life expectancy of greater than 3 months, and adequate organ function, from centres in Germany and Austria.

Specific targeting of hepatitis C virus core protein by an intracellular single-chain antibody of human origin.

The hepatitis C virus (HCV) core protein is essential for viral genome encapsidation and plays an important role in steatosis, immune evasion, and hepatocellular carcinoma. It may thus represent a promising therapeutic target to interfere with the HCV life-cycle and related pathogenesis. In this study, we used phage display to generate single-chain variable domain antibody fragments (scFv) to the core protein from bone marrow plasma cells of patients with chronic hepatitis C.

Relapse to prior therapy is the most important factor for the retreatment response in patients with chronic hepatitis C virus infection.

Background: Treatment options for hepatitis C have developed rapidly in the past decade. The current treatment of choice is a combination of pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin. With the development of more therapy options, patients who failed in prior therapy hope to clear hepatitis C virus by undergoing a more effective retreatment regime.

Treatment of chronic hepatitis delta with pegylated interferon-alpha2b.

Background/aims: Chronic hepatitis D is difficult to treat. The present pilot study investigated the efficacy and tolerability of pegylated (PEG)-interferon (IFN)-alpha2b in chronic hepatitis D.

Patients And Methods: Twelve patients with chronic hepatitis D were prospectively treated with 1.

[Update hepatitis D].

The relevance of chronic hepatitis delta results from its high morbidity. Prevalence of hepatitis D decreases in classic endemic areas of the Mediterranean Basin, but increases in Eastern European countries. Hepatitis D is mainly a disease of immigrants in Germany.

Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin.

Background & Aims: The treatment of patients infected with hepatitis C virus (HCV) type 1 remains a challenge necessitating innovative strategies to improve treatment outcome. The extension of treatment duration beyond 48 weeks is one possible strategy to address this problem.

Methods: The efficacy and safety of 48 weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with pegylated-interferon-alfa-2a (180 microg/wk) plus ribavirin (800 mg/day) were studied in treatment-naive patients with HCV type 1 infection.

Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C.

Background & Aims: Standard therapy of patients with chronic hepatitis C virus (HCV) infected with HCV genotype-2 or -3 is the combination of pegylated interferon-alpha and ribavirin for 24 weeks. Whether shorter treatment durations are possible for these patients without compromising sustained virologic response rates is unknown.

Methods: Patients chronically infected with HCV-2 (n = 39), HCV-2/3 (n = 1), or HCV-3 (n = 113) were treated with peginterferon-alpha-2a (180 microg/wk) plus ribavirin 800-1200 mg/day.

SEN virus has an adverse effect on the survival of HIV-positive patients.

Background: Patients infected with HIV are often coinfected with other viruses.

Objective: To investigate the effect of SEN virus (SENV) strains D and H on mortality in HIV-positive patients.

Methods: A total of 217 HIV-positive patients were analysed retrospectively after first presentation and blood sampling (January 1997 to July 1997) and the effect of coinfection with SENV-D and SENV-H on survival was examined.

SEN virus seroprevalence in HIV positive patients: association with immunosuppression and HIV-replication.

Background: Patients infected with HIV are often co-infected with other viruses. SEN virus (SENV) was isolated from a HIV positive patient with intravenous drug use and post-transfusion hepatitis. SENV strains D and H seem to be relevant for the development of post-transfusion hepatitis.

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration.

Aim: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-alpha) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.

Methods: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.

SEN virus infection.

The SEN virus (SEN-V) belongs to a recently discovered group of DNA viruses whose members (SEN-V-D and SEN-V-H) are associated with post-transfusion hepatitis. It is a single-stranded circular, non-enveloped DNA virus of approximately 3600 to approximately 3800 nucleotides with at least three open reading frames (ORFs). Eight different strains of SEN-V have been identified and provisionally classified as members of the Circoviridae family, a group of small, single-stranded, non-enveloped circular DNA viruses that includes the TT virus (TTV), TUS01, SANBAN, PMV and YONBAN.

Psychomotor slowing in hepatitis C and HIV infection.

Background: Both HIV and hepatitis C virus (HCV) may enter the central nervous system and cause cognitive and/or motor dysfunction. There are limited data on cognition and no data on motor performance in HIV/HCV-coinfected patients.

Objective: To provide data on cognition and motor performance in HIV/HCV infected patients.

Abrogation of hepatitis C virus NS3 helicase enzymatic activity by recombinant human antibodies.

The hepatitis C virus (HCV) NS3 protein possesses both protease and helicase activities and is essential for virus replication and maturation. Specific inhibition of NS3 enzymatic activity can be achieved by antibody binding. Transduction of hepatocytes with encoding cDNA leading to intracellular expression of antibody fragments is expected to terminate HCV replication in infected cells.

Combination treatment of IFNalpha2b and ribavirin in patients with chronic hepatitis C and persistently normal ALTs.

Combination therapy of interferon-alpha2b and ribavirin was prospectively evaluated in 20 patients with chronic replicative hepatitis and persistently normal ALTs. Patients with normal ALTs on three or more occasions within 6 months received interferon-alpha2b 3 MU three times a week with ribavirin 1000-1200 mg everyday for 12 months and had a follow-up of 6 months. HCV genotype 1 was found in 16, and HCV genotype 2 or 3 in 4 patients.