Eckardt John R
The Center for Cancer Care and Research, 12855 North Forty Drive, Suite 200, St. Louis, Missouri 63141, USA.
Oncologist. 2004;9 Suppl 6:25-32. doi: 10.1634/theoncologist.9-90006-25.
Small cell lung cancer (SCLC) is an aggressive tumor that often metastasizes before the primary cancer is diagnosed. Patients with SCLC are typically elderly and often have comorbidities that may predispose them to adverse events during therapy. Although topotecan (Hycamtin; GlaxoSmithKline; Philadelphia, PA), 1.5 mg/m(2)/day via a 30-minute i.v. infusion on days 1-5 of a 21-day cycle, is a standard therapy for relapsed SCLC, this regimen can result in significant neutropenia, especially in previously treated patients. This hematologic toxicity is noncumulative and reversible, but its management can be challenging in this poor-prognosis population. Therefore, alternate treatment regimens have been investigated. Weekly topotecan (4.0 mg/m(2)) is currently investigational and has shown promising activity and favorable tolerability in patients with relapsed ovarian cancer, another aggressive malignancy with a poor prognosis. Preliminary results from a phase II trial of weekly bolus topotecan (4.0 mg/m(2)) in patients with recurrent SCLC were recently reported, and this regimen was generally well tolerated. Furthermore, weekly topotecan has been successfully included in several combination therapy regimens in patients with a variety of solid tumors. In untreated SCLC patients, a combination regimen of weekly topotecan, paclitaxel (Taxol; Bristol-Myers Squibb; Princeton, NJ), and cisplatin (Platinol; Bristol-Myers Squibb) was explored and found to be well tolerated and active in patients with extensive and limited-stage disease. Further clinical trials of weekly topotecan and regimens that include weekly topotecan in the SCLC setting are warranted.
小细胞肺癌（SCLC）是一种侵袭性肿瘤，常在原发性癌症被诊断之前就发生转移。SCLC患者通常为老年人，且常常伴有合并症，这些合并症可能使他们在治疗期间易发生不良事件。尽管拓扑替康（Hycamtin；葛兰素史克公司；宾夕法尼亚州费城），以1.5mg/m²/天的剂量在21天周期的第1 - 5天通过30分钟静脉输注给药，是复发性SCLC的标准治疗方法，但该方案可导致显著的中性粒细胞减少，尤其是在先前接受过治疗的患者中。这种血液学毒性是非累积性且可逆的，但其管理在这个预后较差的人群中可能具有挑战性。因此，人们对替代治疗方案进行了研究。每周一次的拓扑替康（4.0mg/m²）目前正处于研究阶段，并且在复发性卵巢癌患者中已显示出有前景的活性和良好的耐受性，卵巢癌是另一种预后较差的侵袭性恶性肿瘤。最近报道了每周一次大剂量拓扑替康（4.0mg/m²）治疗复发性SCLC患者的II期试验的初步结果，该方案总体耐受性良好。此外，每周一次的拓扑替康已成功纳入多种实体瘤患者的几种联合治疗方案中。在未治疗的SCLC患者中，探索了每周一次拓扑替康、紫杉醇（Taxol；百时美施贵宝公司；新泽西州普林斯顿）和顺铂（Platinol；百时美施贵宝公司）的联合方案，发现该方案在广泛期和局限期疾病患者中耐受性良好且有活性。有必要对每周一次拓扑替康以及在SCLC治疗中包含每周一次拓扑替康的方案进行进一步的临床试验。
