A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.
A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.
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对非小细胞肺癌患者进行 9-氨基辣椒碱 (9-AC) 120 小时输注的 II 期试验。
DOI：
10.1023/a:1010674113243
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发表时间：
2001
影响因子：
3.4
通讯作者：
Hoffman,PC
中科院分区：
文献类型：
--
作者：
Vokes,EE;Gordon,GS;Rudin,CM;Mauer,AM;Watson,S;Krauss,S;Arrieta,R;Golomb,HM;Hoffman,PC
在先前的一项II期临床试验中，我们发现合成的拓扑异构酶I抑制剂9-氨基喜树碱（9-AC）输注72小时，对未经治疗的晚期非小细胞肺癌（NSCLC）患者的单药活性为9%。临床前研究表明，更长时间持续输注该药物可能会产生更大的抗肿瘤活性。一项I期研究建议II期剂量为25 μg/m2/hr，持续120 h（3000 μg/m2，持续5天），连续给药2周，每3周为一周期。我们采用该方案，在本试验中入组了13例未经化疗的IIIB期和IV期NSCLC患者：中位年龄67岁（范围57-74岁）; 46%为男性;92%为IV期;中位等位基因1。12例患者在2个周期的治疗后可进行反应和毒性评价。1例患者出现部分缓解。4例患者病情稳定，7例患者病情进展。两个周期后病情稳定或进展的患者不接受额外的9-AC，并给予常规化疗。中位生存时间为10.2个月，一年生存率为28%（95%可信区间，5-58%）。显著毒性包括骨髓抑制、疲乏和厌食。1例患者在第2周期第1周后出现4级血栓性血小板减少，未接受额外治疗。这些数据表明，与简单的72小时给药方案相比，这种延长的给药方案不太可能增加9-AC在NSCLC中非常温和的活性。不建议进一步评估NSCLC中9-AC的价值。
In a previous phase II trial of thesynthetic topoisomerase I inhibitor,9-aminocamptothecin (9-AC), given as a72-h infusion, we identified modestsingle agent activity of 9% in patientswith previously untreated advancednon-small cell lung cancer (NSCLC).Preclinical studies suggested that a moreprolonged continuous infusion of the drugmight lead to greater antitumor activity. Aphase I study recommended a phase II doseof 25 μg/m2/hr for 120 h(3000 μg/m2over 5 days),administered for 2 consecutive weeks of a3-week cycle. We utilized this schedule andenrolled 13 chemotherapy-naıve patientswith Stage IIIB and IV NSCLC in this trial:median age 67 (range 57–74); 46% male;92% stage IV; and median performancestatus 1. Twelve patients are availablefor response and toxicity evaluation after2 cycles of therapy. One patient achieveda partial response. Four patients hadstable disease while seven patients hadprogressive disease. Patients with stableor progressive disease after two cyclesreceived no additional 9-AC, and wereoffered conventional chemotherapy. Themedian survival time was 10.2 months andthe one-year survival rate 28% (95%confidence interval, 5–58%). Significant toxicities includedmyelosuppression, fatigue, and anorexia. One patient had grade 4 neutropeniafollowing the first week of cycle 2, anddid not receive additional therapy. Therewere no neutropenia-related infections.These data suggest that this prolongedschedule is unlikely to increase 9-AC'svery modest activity in NSCLC above thatseen with the simpler 72-hadministration schedule. Furtherevaluation of 9-AC in NSCLC is notrecommended.