CONTINUOUS CARBOPLATIN INFUSION DURING 6 WEEKS RADIOTHERAPY IN LOCALLY INOPERABLE NON-SMALL-CELL LUNG-CANCER - A PHASE-I AND PHARMACOKINETIC STUDY
CONTINUOUS CARBOPLATIN INFUSION DURING 6 WEEKS RADIOTHERAPY IN LOCALLY INOPERABLE NON-SMALL-CELL LUNG-CANCER - A PHASE-I AND PHARMACOKINETIC STUDY
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DOI：
10.1038/bjc.1995.448
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发表时间：
1995-10-01
影响因子：
8.8
通讯作者：
MULDER, NH
中科院分区：
文献类型：
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作者：
GROEN, HJM;VANDERLEEST, AHD;MULDER, NH
一项I期研究对21例未经治疗、局部不能手术的非小细胞肺癌（NSCLC）患者进行了为期6周的动态持续卡铂输注和连续胸部放疗。卡铂的剂量范围为最后21天（第一水平）、最后31天（第二水平）或放射期6周（第三水平）期间15 mg m（-2）天（-1），此后6周放射（第四和第五水平）期间20或25 mg m（-2）天（-1）。总辐射剂量为60 Gy，每天2 Gy(-1)，每周5天（-1）。前3例患者接受无卡铂放疗。世卫组织III/IV级白细胞减少和血小板减少分别发生在20 mg m（-2）天（-1）的6例患者中的2例和6例患者中的1例的最后两个剂量水平，以及所有3例25 mg m（-2）天（-1）的患者中（剂量限制性毒性）。1例局部感染伴锁骨下静脉血栓形成。肺和食道的放射毒性似乎不受卡铂治疗的影响。21例患者中，1例完全缓解（CR）， 10例部分缓解（PR）， 6例病情稳定（SD）， 4例病情进展（PD）。用塞曼校正的原子吸收分光光度法测定最后三个剂量水平的总铂（TPt）和超滤血浆铂（UPt）。在15、20和25 mg m（-2）天（-1）时，6周TPt的平均s.d水平分别为0.76（0.15）、0.78（0.19）和0.90 (0.22)mg l(-1)， UPt为0.10（0.03）、0.12（0.02）和0.20 (0.03)mg l（-1）。三周后，TPt浓度趋于稳定。平均值（s.d.）UPt的CL（TB）为281 +/- 21 ml min(-1)，与肾小球滤过率相关（r = 0.61, P = 0.03）。根据希尔方程定义的s型E（max）模型估计，血小板减少百分比与UPt曲线下面积相关（r = 0.77）。卡铂伴随60 Gy连续放疗的最大耐受剂量为25 mg m（-2）天（-1）；II期或III期研究的推荐剂量为20mg m(-2) day(-1) day，持续6周。
A phase I study was performed in 21 patients with previously untreated, locally inoperable, non-small-cell lung cancer (NSCLC) with ambulatory continuous carboplatin infusion together with continuous thoracic irradiation over 6 weeks. A dose range for carboplatin of 15 mg m(-2) day(-1) during the last 21 days (first level), during the last 31 days (second level), or during 6 weeks of the radiation period (third level) and thereafter 20 or 25 mg m(-2) day(-1) during 6 weeks of radiation (fourth and fifth level) was used. The total radiation dose was 60 Gy given as 2 Gy day(-1) for 5 days week(-1). The first three patients received radiotherapy without carboplatin. WHO grade III/IV leucopenia and thrombocytopenia occurred in the last two dose levels in two out of six and one out of six patients with 20 mg m(-2) day(-1) respectively, and in all three patients with 25 mg m(-2) day(-1) (dose-limiting toxicity). One local infection around the port and a subclavian vein thrombosis occurred. Radiation toxicity of the lung and oesophagus did not seem to be influenced by carboplatin treatment. Out of 21 patients one had a complete response (CR), ten partial response (PR), six stable disease (SD) and four progressive disease (PD). Total (TPt) and ultrafilterable plasma platinum (UPt) were measured in the last three dose levels with atomic absorption spectrophotometry with Zeeman correction. The mean (s.d.) level for TPt for 6 weeks at 15, 20 and 25 mg m(-2) day(-1) was 0.76 (0.15), 0.78 (0.19) and 0.90 (0.22) mg l(-1) for UPt 0.10 (0.03), 0.12 (0.02) and 0.20 (0.03) mg l(-1) respectively. TPt concentration levelled off after 3 weeks. The mean (s.d.) CL(TB) for UPt was 281 +/- 21 ml min(-1) and correlated with glomerular filtration rate (r = 0.61, P = 0.03). As estimated with the sigmoid E(max) model defined by the Hill equation the percentage reduction in platelets correlated with the area under the curve for UPt (r = 0.77). The maximum tolerable dose of carboplatin with concomitant continuous 60 Gy radiotherapy is 25 mg m(-2) day(-1); the recommended dose for phase II or III studies is 20 mg m(-2) day(-1) day for 6 weeks.