ISSN:
1569-8041
Keywords:
breast cancer
;
cyclophosphamide
;
G-CSF
;
paclitaxel
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: The toxicity profile of prolonged infusions of paclitaxel incombination with cyclophosphamide in metastatic breast cancer has already beendefined. The objective of this dose-finding study was to determine the maximumtolerable doses (MTDs) of shorter (three-hour) infusions of paclitaxel incombination with i.v. bolus cyclophosphamide in patients who had previouslyreceived a maximum of one chemotherapy for advanced breast carcinoma. The MTDof the same regimen with granulocyte colony-stimulating factor (G-CSF) supportwas then established. Patients and methods: Eighty women with metastatic breast cancer receiveda total of 352 fully evaluable courses of therapy. The starting doses werepaclitaxel 135 mg/m2 and cyclophosphamide 750mg/m2 given every three weeks. At least three patients weretreated at each dose level and if there were dose-limiting toxic effectsduring the first cycles three additional patients were entered. G-CSF support(5µg/kg s.c.) was added to the second cycle if specific dose-limitingtoxicitieshad occurred during the first cycle. The MTD was defined as the dose level atwhich more than two of six patients presented dose-limiting toxicities duringthe first cycle. Results: Febrile neutropenia (n = 4) and severe thrombocytopenia (n = 1)defined the MTDs of paclitaxel as 200 mg/m2 and ofcyclophosphamide as 2,000 mg/m2, with or without G-CSF inpatients with and, respectively, without prior chemotherapy for advanceddisease. Non-hematologic toxicity was moderate. Recommended doses were 200mg/m2 of paclitaxel and 1,750 mg/m2 ofcyclophosphamide with or without G-CSF in patients with and, respectively,without prior chemotherapy. The overall response rate was 25% and50%, respectively, in patients with and without prior chemotherapy formetastatic disease. Complete remissions (9%) were reported only inpatients without prior chemotherapy; antitumour activity in women withanthracycline-resistant disease, with an 8% response rate (95%CI: 1%–26%), was poor. Conclusions: Paclitaxel at 200 mg/m2 and cyclophosphamideat 1,750 mg/m2 can be safely administered every three weeksto women with advanced breast cancer. The moderate antitumour activityobserved with the schedule tested argues against its use as initial therapyfor advanced breast cancer.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008211629858
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