Smith G M, Child J A, Cullen M H, Bailey N P, Woodruffe C M, Fletcher J, Earl H, Barnard D
General Infirmary, Leeds, U.K.
Hematol Oncol. 1996 Dec;14(4):193-201. doi: 10.1002/(SICI)1099-1069(199612)14:4<193::AID-HON590>3.0.CO;2-G.
In a multi-centre phase I study we investigated the possibility of reducing the interval between courses of standard CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 2 mgs day 1, and prednisolone 40 mg/m2 days 1-8) from 21 days to 15 days and then 10 days using granulocyte colony stimulating factor (r-MetHuG-CSF (Amgen)-filgrastim) to accelerate neutrophil recovery. Patients received CHOP followed by G-CSF 5 micrograms/kg s.c. from day 2 to the day before the next course (e.g. days 2-14 for the 15-day interval). A total of 28 patients with newly diagnosed intermediate grade or high grade NHL were studied. Four patients were studied at a 21-day interval, six patients were treated at a 15-day interval and subsequently six patients at a 10-day interval. Following analysis of this initial cohort, a further 12 patients were evaluated; four at the 15-day interval, and eight at the 10-day interval. No dose-limiting toxicity was seen in the four patients receiving 21-day CHOP. Dose-limiting toxicity was seen in 4/10 patients treated at the 15-day interval (M:F 7:3, median age 55.5, range 39-67 years). This consisted of infection in two patients, recurrent infection and debility in a third, and mucositis in a fourth. Seven patients experienced one or more infectious episodes requiring antibiotics (median number of episodes: 2, range 1-4). Fourteen patients (M:F 4:3, median age 47.5, range 25-63 years) were treated at the 10-day interval. Dose-limiting toxicity was seen in six patients. This consisted of severe mucositis in three patients, neutropenia and thrombocytopenia on two separate occasions in one patient, and steroid-induced gastritis in two patients. Nine patients had one or more documented infections (median: 2, range 1-3) requiring antibiotics, of which six were severe (WHO grade 3 or 4). One patient died of Pneumocystis carinii (PCP) pneumonia. In summary, G-CSF (filgrastim) will facilitate the shortening of the dosage interval between cycles of CHOP chemotherapy due to accelerated hematological recovery. However, non-hematological toxicity due to the shorter dosage interval is increased and infective episodes are frequent.
在一项多中心I期研究中，我们探讨了使用粒细胞集落刺激因子（重组甲硫氨酸人粒细胞集落刺激因子（安进公司）-非格司亭）加速中性粒细胞恢复，从而将标准CHOP方案（环磷酰胺750mg/m²、阿霉素50mg/m²、长春新碱2mg第1天、泼尼松龙40mg/m²第1 - 8天）疗程之间的间隔从21天缩短至15天，然后再缩短至10天的可能性。患者接受CHOP方案治疗，从第2天至下一个疗程前一天皮下注射G-CSF 5μg/kg（例如，间隔15天时为第2 - 14天）。共研究了28例新诊断的中高级别非霍奇金淋巴瘤患者。4例患者按21天间隔进行研究，6例患者按15天间隔治疗，随后6例患者按10天间隔治疗。在对这一初始队列进行分析后，又评估了12例患者；4例按15天间隔，8例按10天间隔。接受21天CHOP方案治疗的4例患者未出现剂量限制性毒性。按15天间隔治疗的10例患者中有4例出现剂量限制性毒性（男:女为7:3，中位年龄55.5岁，范围39 - 67岁）。其中2例患者发生感染，第3例患者反复感染且身体虚弱，第4例患者发生粘膜炎。7例患者经历了一次或多次需要使用抗生素的感染发作（发作次数中位数：2次，范围1 - 4次）。14例患者（男:女为4:3，中位年龄为岁，范围25 - 63岁）按10天间隔治疗。6例患者出现剂量限制性毒性。其中3例患者发生严重粘膜炎，1例患者在两个不同时间出现中性粒细胞减少和血小板减少，2例患者发生类固醇性胃炎。9例患者有一次或多次记录在案的需要使用抗生素的感染（中位数：2次，范围1 - 3次），其中6次为严重感染（世界卫生组织3级或4级）。1例患者死于卡氏肺孢子虫肺炎。总之，由于血液学恢复加速，G-CSF（非格司亭）将有助于缩短CHOP化疗周期之间的给药间隔。然而，给药间隔缩短导致的非血液学毒性增加，且感染发作频繁。
