Multiple cycles of high-dose doxorubicin and cyclophosphamide with G-CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer.
Academic Article
Overview
abstract
BACKGROUND: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. PATIENTS AND METHODS: For mobilisation of PBPC, G-CSF 15 microg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. RESULTS: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose-limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%-97%), with 22% (95% CI: 3%-41%) complete responses. CONCLUSION: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.
