Budd G T, Atiba J, Silver R T, Palmer G, Armstrong S, Otto K, Presant C
Department of Hematology/Medical Oncology, Cleveland Clinic Foundation, OH 44195, USA.
J Cancer Res Clin Oncol. 1999 Aug-Sep;125(8-9):500-4. doi: 10.1007/s004320050308.
We performed a phase I/II dose-escalation trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) in combination with human recombinant granulocyte-colony-stimulating factor (G-CSF, filgrastim) in patients with advanced breast cancer. The objectives of this trial were (1) to gain experience with filgrastim given to patients with advanced breast cancer and receiving standard-dose CNF, and (2) to determine the maximum tolerated dose of CNF that could be given with filgrastim support by incremental dose escalation of two components of the CNF regimen, cyclophosphamide and mitoxantrone.
Four patients who had received prior therapy for advanced disease received standard-dose CNF with filgrastim support. Sequentially enrolled patients who had received no prior chemotherapy for advanced disease were treated with standard-dose CNF without filgrastim (5 patients), standard-dose CNF with filgrastim (15 patients), or were entered into sequential cohorts of 3-6 patients to be treated with increasing doses of CNF with filgrastim support (29 patients).
The maximum tolerated doses that could be given with filgrastim support were 1500 mg/ml cyclophosphamide, 20 mg/m2 mitoxantrone, and 500 mg/m2 5-FU. Overall, 7 complete (14%) and 13 partial responses (26%) were observed. Despite the use of filgrastim, repeated cycles of CNF at doses of 2000 mg/m2 cyclophosphamide, 25 mg/m2 mitoxantrone, and 500 mg/m2 5-FU could not be given because of neutropenia and thrombopenia. Among 18 patients with bidimensionally measurable disease there were 3 complete (17%) and 5 partial (28%) responses. The median progression-free survival of all patients was 236 days (34 weeks).
The use of filgrastim allows CNF to be given at approximately twice the dose intensity of "standard"-dose CNF. Because nonhematopoietic toxicity was not dose-limiting, further dose escalation of this regimen might be possible with more effective hematopoietic support. The response rate and survival of patients treated in this study were within the range expected with standard-dose chemotherapy.
我们对晚期乳腺癌患者进行了一项环磷酰胺、米托蒽醌和5-氟尿嘧啶（CNF）联合人重组粒细胞集落刺激因子（G-CSF，非格司亭）的I/II期剂量递增试验。该试验的目的是：（1）积累在晚期乳腺癌患者中给予非格司亭并接受标准剂量CNF的经验；（2）通过递增CNF方案的两个组分环磷酰胺和米托蒽醌的剂量，确定在非格司亭支持下可给予的CNF的最大耐受剂量。
4例曾接受晚期疾病前期治疗的患者接受了标准剂量CNF并给予非格司亭支持。依次入组的未接受过晚期疾病前期化疗的患者接受无非格司亭的标准剂量CNF治疗（5例）、有非格司亭的标准剂量CNF治疗（15例），或进入3 - 6例患者的序贯队列，接受递增剂量的CNF并给予非格司亭支持（29例）。
在非格司亭支持下可给予的最大耐受剂量为环磷酰胺1500mg/ml、米托蒽醌20mg/m²、5-氟尿嘧啶500mg/m²。总体上，观察到7例完全缓解（14%）和13例部分缓解（26%）。尽管使用了非格司亭，但由于中性粒细胞减少和血小板减少，无法给予剂量为环磷酰胺2000mg/m²、米托蒽醌25mg/m²和5-氟尿嘧啶500mg/m²的重复周期CNF。在18例有可二维测量疾病的患者中，有3例完全缓解（17%）和5例部分缓解（28%）。所有患者的无进展生存期中位数为236天（34周）。
使用非格司亭可使CNF以约“标准”剂量CNF两倍的剂量强度给药。由于非血液学毒性不是剂量限制性的，通过更有效的造血支持，该方案可能进一步增加剂量。本研究中治疗患者的缓解率和生存率在标准剂量化疗预期的范围内。
