Weaver A, Wrigley E, Watson A, Chang J, Collins C D, Jenkins B, Gill C, Pettengell R, Dexter T M, Testa N G, Crowther D
Cancer Research Campaign Department of Medical Oncology, Christie Hospital, Manchester, UK.
Br J Cancer. 1996 Dec;74(11):1821-7. doi: 10.1038/bjc.1996.637.
We have shown that large numbers of haemopoietic progenitor cells are mobilised into the blood after filgrastim [granulocyte colony-stimulating factor (G-CSF)] alone and filgrastim following cyclophosphamide chemotherapy in previously untreated patients with ovarian cancer. These cells may be used to provide safe and effective haemopoietic rescue following dose-intensive chemotherapy. Using filgrastim alone (10 micrograms kg-1), the apheresis harvest contained a median CFU-GM count of 45 x 10(4) kg-1 and 2 x 10(6) kg-1 CD34+ cells. Treatment with filgrastim (5 micrograms kg-1) following cyclophosphamide (3 g m-2) resulted in a harvest containing 66 x 10(4) kg-1 CFU-GM and 2.4 x 10(6) kg-1 CD34+ cells. There was no statistically significant difference between these two mobilising regimens. We have also demonstrated that dose-intensive carboplatin and cyclophosphamide chemotherapy can be delivered safely to patients with ovarian cancer when supported by peripheral blood progenitor cells and filgrastim. Carboplatin (AUC 7.5) and cyclophosphamide (900 mg m-2) given at 3 weekly intervals with progenitor cell and growth factor support was well tolerated in terms of haematological and systemic side-effects. Double the dose intensity of chemotherapy was delivered compared with our standard dose regimen when the treatment was given at 3 weekly intervals. Median dose intensity could be further escalated to 2.33 compared with our standard regimen by decreasing the interval between treatment cycles to 2 weeks. However, at this dose intensity less than a third of patients received their planned treatment on time. All the delays were due to thrombocytopenia.
我们已经表明,在既往未经治疗的卵巢癌患者中,单独使用非格司亭[粒细胞集落刺激因子(G-CSF)]以及在环磷酰胺化疗后使用非格司亭,可使大量造血祖细胞动员至血液中。这些细胞可用于在剂量密集化疗后提供安全有效的造血救援。单独使用非格司亭(10微克/千克)时,单采收获物中CFU-GM计数中位数为45×10⁴/千克,CD34⁺细胞为2×10⁶/千克。环磷酰胺(3克/平方米)后使用非格司亭(5微克/千克)进行治疗,收获物中含有66×10⁴/千克CFU-GM和2.4×10⁶/千克CD34⁺细胞。这两种动员方案之间无统计学显著差异。我们还证明,当有外周血祖细胞和非格司亭支持时,剂量密集的卡铂和环磷酰胺化疗可安全地用于卵巢癌患者。每3周间隔给予卡铂(AUC 7.5)和环磷酰胺(900毫克/平方米),同时给予祖细胞和生长因子支持,在血液学和全身副作用方面耐受性良好。与我们的标准剂量方案相比,当每3周间隔进行治疗时,化疗的剂量强度提高了一倍。通过将治疗周期之间的间隔缩短至2周,与我们的标准方案相比,中位剂量强度可进一步提高至2.33。然而,在此剂量强度下,不到三分之一的患者按时接受了计划的治疗。所有延迟均归因于血小板减少症。