Relationship between the exposure to cisplatin, DNA-adduct formation in leucocytes and tumour response in patients with solid tumours
Relationship between the exposure to cisplatin, DNA-adduct formation in leucocytes and tumour response in patients with solid tumours
复制标题
DOI：
10.1038/bjc.1996.296
复制
发表时间：
1996-06-01
影响因子：
8.8
通讯作者：
Verweij, J
中科院分区：
文献类型：
--
作者：
Schellens, JHM;Ma, J;Verweij, J
该研究旨在调查实体瘤患者的肿瘤反应与顺铂暴露（血浆中未结合的顺铂曲线下面积，AUC）和白细胞中 DNA 加合物形成（WBC）之间可能的关系。患者每周接受六个疗程的顺铂治疗，剂量为 70 或 80 mg m(-2)。在第一个疗程期间测定 AUC，并在所有疗程期间测定基线、顺铂输注 3 小时后 1 小时 (A(max)) 和 15 小时的 WBC 中 DNA 加合物水平。计算 DNA 加合时间曲线下面积 (AUA)。六个疗程后确定肿瘤反应。 45 名可评估患者接受了 237 个疗程的顺铂治疗。 16 名头颈癌患者接受了 80 mg m(-2) 剂量，29 名患有各种其他肿瘤类型的患者接受了 70 mg m(-2) 加每日 50 mg 口服依托泊苷。有 20 名有反应者（部分和完全）和 25 名无反应者（疾病稳定和进展）。 AUC 变化很大（平均值+/-s.d.=2.48+/-0.51 mu g h(-1) ml(-1)；范围 1.10-3.82），并且与 AUA 密切相关（r=0.78，P
The study was designed to investigate possible relationships between tumour response and exposure to cisplatin (area under the curve of unbound cisplatin in plasma, AUC) and DNA-adduct formation in leucocytes (WBC) in patients with solid tumours. Patients were treated with six weekly courses of cisplatin at a dose of 70 or 80 mg m(-2). The AUC was determined during the first course and DNA-adduct levels in WBC during all courses at baseline, 1 h (A(max)) and 15 h after a 3 h infusion of cisplatin. The area under the DNA-adduct-time curve (AUA) was calculated. The tumour response was determined after six courses. Forty-five evaluable patients received 237 courses of cisplatin. Sixteen patients with head and neck cancer received a dose of 80 mg m(-2) and 29 with various other tumour types received 70 mg m(-2) plus daily 50 mg oral etoposide. There were 20 responders (partial and complete) and 25 non-responders (stable and progressive disease). The AUC was highly variable (mean+/-s.d.=2.48+/-0.51 mu g h(-1) ml(-1); range 1.10-3.82) and was closely correlated with the AUA (r=0.78, P