A phase I trial of AUC-directed carboplatin with infusional doxorubicin and ifosfamide plus G-CSF in patients with advanced gynecologic malignancies.
The effect of the addition of G-CSF to carboplatin, ifosfamide and doxorubicin (CIA) at the maximally tolerated dose (MTD) was studied in a phase I clinical trial. Nine patients with incurable solid tumors were treated: six endometrial and epithelial ovarian cancers, one colon cancer with pelvic masses and two unknown primary cancers. The carboplatin dose was calculated using the Calvert formula and administered in a standard 30-min intravenous infusion. The initial carboplatin dose was AUC 4.0 mg/ml per min. Fixed doses of ifosfamide (1.25 g/m2 per day), mesna (1.0 g/m2 per day, and doxorubicin (15 mg/m2 per day) were combined and given as a 4-day continuous intravenous infusion in an attempt to decrease nonhematologic toxicity. The dose-limiting toxicity of CIA was myelosuppression, mainly neutropenia and thrombocytopenia. Nonhematologic toxicities were hemorrhagic cystitis, weakness, fatigue, and nausea and vomiting. The MTD for CIA was established at the first dose level of carboplatin (4.0 mg/ml per min). Following this, G-CSF was added to the regimen in an unsuccessful effort to escalate the carboplatin dose. Free and total carboplatin pharmacokinetics were determined using flameless atomic absorption spectroscopy. There was one complete response and one partial response among eight evaluable patients. Both responding patients had advanced ovarian cancer. We conclude that carboplatin dose intensification beyond an AUC of 4.0 mg/ml per min is not made feasible by the addition of G-CSF to infusional doxorubicin and ifosfamide in patients with advanced gynecologic cancer.
Lopez
A M
AM
Department of Medicine, College of Medicine, University of Arizona, Tucson 85724, USA.
Ketchum
M
M
Nichols
H
H
Xu
M J
MJ
Peng
Y M
YM
Dorr
R
R
Alberts
D S
DS
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001772:Blood Cell Count; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D016190:Carboplatin; D007069:Ifosfamide