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Dose escalation study of carboplatin and cyclophosphamide with filgrastim support: a phase I study.
- Source :
-
American journal of clinical oncology [Am J Clin Oncol] 1998 Jun; Vol. 21 (3), pp. 263-9. - Publication Year :
- 1998
-
Abstract
- This clinical trial was designed to explore dose escalation of carboplatin and cyclophosphamide when supported with filgrastim. Twenty-seven patients who had advanced solid tumors received up to six cycles of treatment; a total of 92 cycles of chemotherapy were delivered. Two control groups received standard-dose carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2), with and without filgrastim. Subsequently, the doses of both carboplatin and cyclophosphamide were increased simultaneously by 50% of the standard dose in sequential cohorts. Doses of up to 2.5 times the standard dose were explored. A final dose of carboplatin, 600 mg/m2, and cyclophosphamide, 1,500 mg/m2, was tested in 4 patients. The duration of neutropenia was brief, even at the highest dose levels. The mean duration of grade 3 or 4 neutropenia was 5.8 days at standard dose without filgrastim and 5.4 days at 2.5 times standard dose with filgrastim. More severe neutropenia was more prolonged at higher doses but remained brief in duration. The mean duration of neutropenia of less than 100 x 10(6)/l was 0.4 days at standard dose without filgrastim and 1.3 days at 2.5 times standard dose. There was no evidence of cumulative neutropenia over repeated cycles of treatment. In contrast, thrombocytopenia was both dose limiting and cumulative. The mean duration of grade 3 or 4 thrombocytopenia was 1.6 days at standard dose and 9.6 days at 2.5 times standard dose. An average of 2.3 platelet transfusions per cycle of treatment was required at the highest dose. Thrombocytopenia was worse with repetitive cycles of therapy. The mean duration of grade 3 or 4 thrombocytopenia was 2.2 days after the first cycle of chemotherapy and 7.8 days after cycle four. The maximum tolerated dose, as defined prospectively, was not reached but further dose escalation was not thought to be warranted because of the severity of thrombocytopenia. When supported with filgrastim, carboplatin and cyclophosphamide can be administered safely with substantially increased dose and acceptable toxicity.
- Subjects :
- Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols adverse effects
Carboplatin administration & dosage
Carboplatin adverse effects
Cyclophosphamide administration & dosage
Cyclophosphamide adverse effects
Dose-Response Relationship, Drug
Female
Filgrastim
Granulocyte Colony-Stimulating Factor administration & dosage
Granulocyte Colony-Stimulating Factor adverse effects
Humans
Male
Middle Aged
Recombinant Proteins
Thrombocytopenia chemically induced
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0277-3732
- Volume :
- 21
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 9626795
- Full Text :
- https://doi.org/10.1097/00000421-199806000-00012