Dose escalation study of recombinant human granulocyte-colony-stimulating factor (KRN8601) in patients with advanced malignancy.
To evaluate the toxicity and efficacy of recombinant human granulocyte-colony-stimulating factor (rh G-CSF) administered with intensive chemotherapy, 39 patients with advanced pulmonary cancers were enrolled in a dose escalation trial of rh G-CSF. Three days after initiation of chemotherapy rh G-CSF was administered i.v. for 14 consecutive days at five dose levels (50-800 micrograms/m2). Absolute neutrophil counts showed a dose-dependent increase with an increasing dose of rh G-CSF and the durations of neutropenia (less than 1000/mm3) shortened significantly at doses of 200, 400, and 800 micrograms/m2 compared to those at 50 micrograms/m2 (P less than 0.01). The duration of neutropenia was shortened significantly at all five dose levels following treatment with rh G-CSF compared to treatment without rh G-CSF (P less than 0.05). Adverse side effects associated with rh G-CSF administration were fever higher than 38 degrees C (21%), chest pain, and low back pain (13%). No intolerable side effects were experienced. It can be concluded that rh G-CSF is effective in shortening the duration of neutropenia following intensive chemotherapy at a dose level of 100 to 200 micrograms/m2 i.v. a 400-micrograms/m2 dose of rh G-CSF is recommended in patients with prior treatment because of the possibility of a lower bone marrow response.
Eguchi
K
K
Section of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Sasaki
S
S
Tamura
T
T
Sasaki
Y
Y
Shinkai
T
T
Yamada
K
K
Soejima
Y
Y
Fukuda
M
M
Fujihara
Y
Y
Kunitou
H
H
D000328:Adult; D000368:Aged; D003115:Colony-Stimulating Factors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor