Phase I study of pharmacologically based dosing of carboplatin with filgrastim support in women with epithelial ovarian cancer.
OBJECTIVE
The aim of this study was to increase the dose intensity of carboplatin in women with International Federation of Gynecology and Obstetrics (FIGO) Stage Ic-IV epithelial ovarian cancer with the use of granulocyte colony-stimulating factor (G-CSF; filgrastim; Amgen, Thousand Oaks, CA).


METHODS
A phase I study of escalating target area under the curves (AUCs) of carboplatin with G-CSF (filgrastim) ws undertaken. The target AUCs were 5 mg/mL.min every 21 days for four cycles, 5 mg/mL.min every 14 days for four cycles, 7 mg/mL.min every 14 days for four cycles, 9 mg/mL.min every 14 days for four cycles, and 11 mg/mL.min every 14 days for four cycles. G-CSF was given at a dose of 5 microg/kg/d starting 24 hours after carboplatin administration and lasting until 24 hours before the next cycle and until day 14 after the last cycle.


RESULTS
We were able to escalate to an AUC level of 9 mg/mL.min every 14 days for four cycles. At this dose, severe thrombocytopenia, that necessitated dosage delays, and failure to give subsequent cycles of carboplatin were observed. We then reduced the AUC level to 8 mg/mL.min every 14 days for four cycles. However, severe thrombocytopenia was also observed at this level.


CONCLUSIONS
An AUC of 7 mg/mL.min every 14 days for four cycles is the maximum tolerated AUC level that can be achieved with G-CSF. Further escalations may be possible using either combinations of cytokines or peripheral stem-cell collections.
Lind
M J
MJ
Department of Oncology, Northern Centre for Cancer Treatment, Newcastle General Hospital, United Kingdom.
Ghazal-Aswad
S
S
Gumbrell
L
L
Fishwick
K
K
Craigs
D
D
Millward
M J
MJ
Bailey
N P
NP
Dore-Green
F
F
Chapman
F
F
Simmons
D
D
Proctor
M
M
Oakey
A
A
Robson
L
L
Middleton
I
I
McCann
E
E
Sinha
D
D
Calvert
A H
AH
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin; D000069585:Filgrastim