Lenograstim. A review of its pharmacological properties and therapeutic efficacy in neutropenia and related clinical settings.
Lenograstim is a recombinant glycosylated human granulocyte colony-stimulating factor (rHuG-CSF) which principally regulates the formation and function of neutrophils. Like other colony-stimulating factors (CSFs), lenograstim has been developed for the prevention and treatment of iatrogenic and disease-related neutropenic conditions. In phase III clinical studies, prophylactic administration of lenograstim shortened the duration of chemotherapy-induced neutropenia in patients with nonmyelogenous cancers who received standard-dose chemotherapy or myeloablative regimens followed by bone marrow transplantation (BMT). A decrease in the incidence of infection after standard regimens and fewer days with infectious and febrile neutropenic episodes during recovery from BMT occurred concomitantly with the amelioration of neutropenia. In each setting, the decrease in morbidity was associated with shorter hospitalisation times and reduced administration of parenteral antibacterial agents. As with another rHuG-CSF, filgrastim, bone pain (non-serious) was the most common adverse reaction to lenograstim therapy. This occurred in 13% of lenograstim recipients and 5% of placebo recipients treated for chemotherapy-induced neutropenia with standard regimens. Lenograstim may facilitate dose optimisation and permit limited dose intensification of standard chemotherapy. Furthermore, the drug, used alone or in combination with chemotherapy, is effective in mobilising peripheral blood progenitor cells (PBPCs) for subsequent reinfusion. The latter is a promising technique which may supplement or ultimately replace BMT for stem cell rescue after myeloablative chemotherapy. However, it has yet to be established whether the dose intensification achievable with lenograstim and/or stem cell rescue has a material effect on relapse-free and survival times. Preliminary data suggest that lenograstim is effective in increasing the neutrophil count in patients with severe chronic neutropenia (Kostmann's syndrome), as well as patients with AIDS or AIDS-related complex with zidovudine-induced neutropenia. Thus, lenograstim, like other CSFs, is a valuable adjunct to cytotoxic chemotherapy for the treatment of nonmyelogenous cancers, including myeloablative regimens followed by stem cell rescue with BMT and/or PBPC infusion. Future clinical experience is likely to confirm the usefulness of the drug in the management of disease-related neutropenia, myeloid disorders and neutropenia in patients with AIDS.
Frampton
J E
JE
Adis International Ltd, Auckland, New Zealand.
Yarker
Y E
YE
Goa
K L
KL
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001855:Bone Marrow Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D000078224:Lenograstim; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim