Yoshida O, Kakehi Y, Arai Y, Tomoyoshi T, Okada Y, Matsuda T, Mikami O, Fukuyama T, Hida S, Okabe T
Department of Urology, Kyoto University, Japan.
Int J Urol. 1995 Nov;2(5):316-21.
Despite improvement in the response rate and protraction of the progression-free period of urothelial cancer produced by chemotherapy, severe bone marrow suppression often results in delays in the initiation of treatment cycles and/or decreases in drug dosages. Reduction of leukopenia during chemotherapy has been demonstrated by the combined administration of granulocyte colony-stimulating factor (G-CSF) in various malignancies.
A phase I/II study was conducted to assess whether the interval between cycles of CISCA (cyclophosphamide, doxorubicin, cisplatin) chemotherapy could be shortened under support of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for urothelial cancer. Three or more patients with transitional cell carcinoma of the urinary tract were allocated to each of four different treatment intervals (step 1: 28 days, step 2: 21 days, step 3: 17 days, and step 4: 14 days) by reducing the interval in a step-wise manner. Two mg/kg/day of a rhG-CSF, lenograstim, was injected subcutaneously on days 3 to 16 (until day 14 for the 14-day interval group).
Sixteen patients were enrolled, four patients were treated with the step 1 protocol, five with step 2, four with step 3, and three with step 4. Leukopenia/neutropenia was the most severe toxic reaction, but none of the patients at any step manifested neutropenia of WHO grade 4 for more than four days. There were no significant differences in the hematological and nonhematological toxicities among the 4 steps. Seven of eight patients with measurable diseases were treated with CISCA on shortened schedules (steps 2-4), and one complete remission (CR) and four partial responses (PR) were demonstrated.
CISCA chemotherapy supported by rhG-CSF was safely shortened to a 14-day interval in the pilot study. The potential role of rhG-CSF in shortening the interval of CISCA, as well as the benefit of the intensified schedule, remains to be clarified.
尽管化疗使尿路上皮癌的缓解率有所提高，无进展期得以延长，但严重的骨髓抑制常导致治疗周期启动延迟和/或药物剂量降低。在各种恶性肿瘤中，联合应用粒细胞集落刺激因子（G-CSF）已证明可减少化疗期间的白细胞减少。
开展一项I/II期研究，以评估在重组人粒细胞集落刺激因子（rhG-CSF）支持下，尿路上皮癌患者接受CISCA（环磷酰胺、阿霉素、顺铂）化疗时，能否缩短化疗周期之间的间隔时间。通过逐步缩短间隔时间，将三名或更多例尿路移行细胞癌患者分配至四个不同的治疗间隔组（步骤1：28天，步骤2：21天，步骤3：17天，步骤4：14天）。在第3至16天（14天间隔组至第14天）皮下注射rhG-CSF来格司亭，剂量为2mg/kg/天。
共纳入16例患者，4例接受步骤1方案治疗，5例接受步骤2治疗，4例接受步骤3治疗，3例接受步骤4治疗。白细胞减少/中性粒细胞减少是最严重的毒性反应，但任何步骤的患者均未出现超过4天的WHO 4级中性粒细胞减少。4个步骤之间的血液学和非血液学毒性无显著差异。8例可测量疾病患者中的7例按缩短方案（步骤2至4）接受了CISCA治疗，出现1例完全缓解（CR）和4例部分缓解（PR）。
在该初步研究中，rhG-CSF支持下的CISCA化疗安全地缩短至14天间隔。rhG-CSF在缩短CISCA间隔时间方面的潜在作用以及强化方案的益处仍有待阐明。
