Prospective Pilot Study of Recombinant Granulocyte-Macrophage Colony-Stimulating Factor and Interferon-γ in Patients With Inoperable Hepatocellular Carcinoma

Autor: Cornelia Lichtenberger, Peter Ferenci, Maximilian Schöniger-Hekele, Georg Oberhuber, Andreas Katz, Thomas Waldhoer, Margareta Holub, Alfred Gangl, A. M. Herneth, Walter Reinisch, Christian A. Mueller
Rok vydání: 2002
Předmět:
Liver Cirrhosis
Male
Cancer Research
medicine.medical_treatment
Pilot Projects
Gastroenterology
Leukocyte Count
HLA Antigens
Immunology and Allergy
Life Tables
Interferon gamma
Prospective Studies
Immunologic Surveillance
Aged
80 and over
Immunogenicity
Liver Neoplasms
Palliative Care
Remission Induction
Middle Aged
Recombinant Proteins
Neoplasm Proteins
Treatment Outcome
Tolerability
Hepatocellular carcinoma
Female
Chemokines
CXC
medicine.drug
Adult
medicine.medical_specialty
Carcinoma
Hepatocellular
Combination therapy
Injections
Subcutaneous
Immunology
Interferon-gamma
Adjuvants
Immunologic
Antigens
CD
Internal medicine
medicine
Humans
Karnofsky Performance Status
Adverse effect
Aged
Salvage Therapy
Pharmacology
business.industry
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
medicine.disease
Survival Analysis
Surgery
Discontinuation
Chemokine CXCL10
business
Biomarkers
Zdroj: Journal of Immunotherapy. 25:489-499
ISSN: 1524-9557
DOI: 10.1097/00002371-200211000-00005
Popis: Interferon (IFN)-gamma and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) enhance tumor immunogenicity. The authors assessed tolerability and effectiveness of a combination therapy of these recombinant human (rh) cytokines in patients with inoperable hepatocellular carcinoma (HCC). In a monocentric, open, nonrandomized pilot study, rhGM-CSF (5 microg/kg qd, Monday and Tuesday) and rhIFN-gamma (100 microg qd, Wednesday and Thursday) were subcutaneously administered in 9-week cycles. Primary objective was survival, as secondary outcomes volumetric changes of tumor mass and biologic parameters reflecting systemic immunologic or local tumor responses were measured. Only patients with complete response (CR), partial response (PR), or stable disease (SD) proceeded to new treatment cycles. Fifteen patients (median 63 years, range 46-74 years, all men) were enrolled. Survival after the first cycle was 80% with SD in 9 of 15 patients (60%). PR was detected in one patient after the second cycle. Two patients finished five treatment cycles. Overall survival at 26 and 52 weeks was 40% and 20%, respectively. Median survival in patients with inducible HLA-DR on hepatoma cells (40%) was increased (42 weeks, 27-100) as compared with HLA-DR negative cases (60%; 13 weeks, 8-23; p0.0001), and a control group (p = 0.01). Parameters reflecting systemic immunomodulatory activities were not associated with clinical outcome. In 13 of 15 patients (87%), adverse events were reported, all less than grade 2 and none requiring therapy discontinuation. Immunotherapeutic approaches hold promise to prolong survival in selected patients with advanced HCC who respond by enhanced tumor immunogenicity.
Databáze: OpenAIRE
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