Fukuoka M, Niitani H, Suzuki A, Motomiya M, Hasegawa K, Nishiwaki Y, Kuriyama T, Ariyoshi Y, Negoro S, Masuda N
CPT-II Lung Cancer Study Group, Tokyo, Japan.
J Clin Oncol. 1992 Jan;10(1):16-20. doi: 10.1200/JCO.1992.10.1.16.
Camptothecin-11 (CPT-11) is a new semisynthetic derivative of CPT, and has been shown to inhibit DNA topoisomerase I and to have a strong antitumor activity with low toxicity in murine tumors. To evaluate the effectiveness of CPT-11 in patients with non-small-cell lung cancer (NSCLC), a phase II study was conducted between April 1989 and February 1990.
Seventy-three patients were entered onto the study. All patients had had no previous therapy and had measurable disease. Their median age was 67 years (range, 34 to 75 years). Fifty-four patients had a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale, and 19 had a PS of 2. CPT-11 was given at a dose of 100 mg/m2 by intravenous 90-minute infusion once a week. The dose of CPT-11 was modified based on the WBC count obtained on the day of drug administration.
Of 72 assessable patients, 23 (31.9%) showed a partial response (95% confidence interval, 20.2% to 43.6%). Of 40 patients with a stage IV disease, 13 (32.5%) responded. Response rates for patients with PS 0 or 1 and those with PS 2 did not differ (34.0% and 26.3%, respectively). The median duration of response in patients showing a PR was 15 weeks. The median survival time for all patients was 42 weeks. The major toxicities were leukopenia and diarrhea. Grade 3 or 4 leukopenia and diarrhea occurred in 18 patients (25%) and 15 patients (21%), respectively. These toxicities were unpredictable. Other toxicities of greater than or equal to grade 3 included nausea/vomiting (22%), anemia (15%), alopecia (4%) and pneumonitis (3%). One patient died of pulmonary toxicity (interstitial pneumonitis).
CPT-11 is a very active agent for NSCLC with acceptable toxicities. Further trials in combination with other agents for this disease are warranted.
喜树碱-11（CPT-11）是喜树碱的一种新型半合成衍生物，已显示出可抑制DNA拓扑异构酶I，并在鼠类肿瘤中具有低毒性的强抗肿瘤活性。为评估CPT-11对非小细胞肺癌（NSCLC）患者的疗效，于1989年4月至1990年2月进行了一项II期研究。
73例患者进入该研究。所有患者此前均未接受过治疗且具有可测量的病灶。他们的中位年龄为67岁（范围34至75岁）。54例患者在东部肿瘤协作组（ECOG）量表上的体能状态（PS）为0或1，19例患者的PS为2。CPT-11以100mg/m²的剂量通过静脉90分钟输注，每周一次。CPT-11的剂量根据给药当天测得的白细胞计数进行调整。
在72例可评估患者中，23例（31.9%）显示部分缓解（95%置信区间，20.2%至43.6%）。在40例IV期疾病患者中，13例（32.5%）有反应。PS为0或1的患者与PS为2的患者的缓解率无差异（分别为34.0%和26.3%）。显示PR的患者的中位缓解持续时间为15周。所有患者的中位生存时间为42周。主要毒性为白细胞减少和腹泻。3级或4级白细胞减少和腹泻分别发生在18例患者（25%）和15例患者（21%）中。这些毒性是不可预测的。大于或等于3级的其他毒性包括恶心/呕吐（22%）、贫血（15%）、脱发（4%）和肺炎（3%）。1例患者死于肺部毒性（间质性肺炎）。
CPT-11是一种对NSCLC非常有效的药物，毒性可接受。有必要针对该疾病与其他药物联合进行进一步试验。
