ISSN:
1432-0843
Keywords:
Key words Carboplatin
;
Ifosfamide
;
Doxorubicin
;
G-CSF
;
Combination regimen
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002800000154
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