The clinical use of the biologic response modifiers
filgrastim,
sargramostim, and
regramostim is reviewed. All circulating blood cells are derived from totipotent hematopoietic stem cells. Various biologic response modifiers, including
lymphokines and
colony-stimulating factors, regulate and activate the lymphoid and myeloid cells of the blood. One of the more important types of blood cell for fighting
infection is the neutrophil. Patients with low neutrophil concentrations are at high risk of developing neutropenic
fevers and
infections. The
colony-stimulating factors filgrastim,
sargramostim, and
regramostim increase the production of circulating neutrophils, and this action is clinically useful in patients undergoing myelosuppressive
antineoplastic therapy or
bone marrow transplantation and in patients with the
acquired immunodeficiency syndrome. Clinical studies of these agents in comparison with antimicrobial prophylaxis or placebo have shown a decreased rate of neutropenic-associated hospitalizations and
infections. These agents are also under study for dose intensification of
antineoplastics in patients with various solid
tumors and for augmenting patient responses to antimicrobial
therapy in situations where there is high risk of morbidity and mortality.
Sargramostim and
regramostim are both granulocyte-macrophage
colony-stimulating factors that differ in their degree of glycosylation and source of production, and at high doses they can cause life-threatening adverse effects because they stimulate the production of a broad range of leukocytes.
Filgrastim, which stimulates only the production of neutrophils, has been better tolerated, especially at higher doses. Biologic response modifiers hold much promise for improving
therapy of certain clinical conditions by decreasing myelosuppressive complications and enhancing responses to other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)