USE OF PERIPHERAL-BLOOD PROGENITOR CELLS ABROGATES THE MYELOTOXICITY OF REPETITIVE OUTPATIENT HIGH-DOSE CARBOPLATIN AND CYCLOPHOSPHAMIDE CHEMOTHERAPY

被引:83
|
作者
TEPLER, I
CANNISTRA, SA
FREI, E
GONIN, R
ANDERSON, KC
DEMETRI, G
NILOFF, J
GOODMAN, H
MUNTZ, H
MUTO, M
SHEETS, E
ELIAS, AD
MAZANET, R
WHEELER, C
AYASH, L
SCHWARTZ, G
MCCAULEY, M
GAYNES, L
HARVEY, S
SCHNIPPER, LE
ANTMAN, KH
机构
[1] HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT MED, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT BIOSTAT, BOSTON, MA 02115 USA
[3] BETH ISRAEL HOSP, DIV GYNECOL ONCOL, BOSTON, MA 02215 USA
[4] HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DIV GYNECOL ONCOL, BOSTON, MA 02115 USA
关键词
D O I
10.1200/JCO.1993.11.8.1583
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment. Patients and Methods: An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 μg/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting. Results: In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/μL (6.5 v 1 day; P = .016), days to platelets more than 50,000/μL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/μL) (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose- limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/μL or ANC less than 500/μL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1). Conclusion: These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.
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收藏
页码:1583 / 1591
页数:9
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