Hematopoietic colony-stimulating factors. Uses in combination with standard chemotherapeutic regimens and in support of dose intensification.
BACKGROUND
Three hematopoietic colony-stimulating factors (CSF) are currently approved for clinical use and several more are being used in clinical trials. These factors have impressive quantitative and/or functional effects on their respective target cell lines, but their best clinical uses have not been defined.


METHODS
The literature regarding the use of CSF in standard chemotherapy is reviewed data and from early Phase I-II studies the use of granulocyte-macrophage CSF (GM-CSF) in support of dose intensification without progenitor cell replacement are presented. Dose intensive cyclophosphamide (5000 mg/m2), etoposide (1500 mg/m2), and cisplatin (150 mg/m2) (DICEP) were administered during 3 days, followed by CSF until hematologic recovery was achieved. Patients had advanced types of cancer unlikely to respond to standard chemotherapy.


RESULTS
CSF can shorten the duration of leukocyte nadirs when given with standard chemotherapy, but a benefit to patients in terms of improved survival or quality of life has not been shown. Dose intensification has increased partial and complete response rates in several tumor types. The higher complete remission rate may translate into improved survival; no convincing data have been published to date supporting that possibility. The duration of severe leukopenia (absolute neutrophil count, less than 100/microliters) after DICEP can be shortened from 8.5 days to 5-6 days with either granulocyte CSF (G-CSF) or GM-CSF. GM-CSF has been shown to decrease the duration of hospital stay from 18.7 to 9.6 days and to decrease the need for readmittance to the hospital for cytopenic fever. A high complete remission rate (35%) was seen in patients with breast cancer and durable complete remissions were achieved in patients with refractory non-Hodgkin lymphoma.


CONCLUSIONS
CSF shortens the duration of postchemotherapy leukocyte nadirs and allows maintenance of dose when this is essential for a beneficial outcome. Substantial dose escalations are also possible with CSF support and can produce a high complete response rate that offers hope for improved survival in selected patients.
Neidhart
J A
JA
University of New Mexico Cancer Center, Albuquerque 87131-5636.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor