Carboplatin and granulocyte colony-stimulating factor as first-line treatment for epithelial ovarian cancer: a phase I dose-intensity escalation study.
A phase I study of frequently administered carboplatin with recombinant human granulocyte colony-stimulating factor (filgrastim) has been performed in patients with newly diagnosed epithelial ovarian cancer. Recombinant human granulocyte colony-stimulating factor was administered at a dose of 5 micrograms/kg/d for days 1 through 12 after carboplatin treatment. Carboplatin doses were calculated using a pharmacokinetic formula on an area under the curve (AUC) basis. Four doses of carboplatin were planned for each patient. The first cohort of patients received an AUC of 5 mg/mL x min every 3 weeks. Subsequently four additional cohorts received AUCs of 5, 7, 9, and 8 every 2 weeks. Non-hematologic toxicities were mild and not significant. The dose-limiting toxicity was thrombocytopenia and occurred at an AUC of 9. Most patients could complete treatment at an AUC of 7. Results for AUC 8 are awaited. Complete and partial responses were seen in most patients at all dose levels.
Calvert
A H
AH
Newcastle General Hospital, Newcastle upon Tyne, UK.
Lind
M J
MJ
Ghazal-Aswad
S
S
Gumbrell
L
L
Millward
M J
MJ
Bailey
N P
NP
Doré-Green
F
F
Chapman
F
F
Simmons
D
D
Proctor
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017713:Platelet Transfusion; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000628:therapy; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin; D000069585:Filgrastim