Lowenbraun S, Birch R, Buchanan R, Krauss S, Durant J, Perez C, Mill W, Vollmer R, Ogden L
Cancer. 1984 Dec 1;54(11):2344-50. doi: 10.1002/1097-0142(19841201)54:11<2344::aid-cncr2820541106>3.0.co;2-c.
From April, 1979 to November, 1981, 293 patients with small cell lung carcinoma (SCLC) were entered on a randomized, controlled study comparing the two induction regimens of high-dose CAV (HD-CAV) (cyclophosphamide [CTX] 1200 mg/m2, doxorubicin [ADR] 70 mg/m2 and vincristine [VCR] 1 mg/m2 intravenously (IV) on days 1 and 21) versus, conventional-dose CAV + VP-16 (etoposide) (CAV-VP) (CTX 1000 mg/m2, ADR 40 mg/m2, VCR 1 mg/m2 IV on days 1 and 21 with VP-16 100 mg/m2 on days 1-3, and 21-23). Responding and stable patients were continued on conventional-dose CAV for 5 consolidation courses. Prophylactic brain irradiation delivered after the first consolidation course in responders was optional. Patients were included in the study if they had extensive disease (i.e., beyond one hemithorax), no prior chemotherapy, or radiotherapy and performance status of 50 or above. After 2 induction courses, 215 cases are evaluable. Of these, 76 of 106 (72%) patients treated with HD-CAV have responded (greater than 50% regression), including 13 complete responders (CRs) versus 80 of 108 (74%) patients on CAV-VP, including 15 CRs. Of the 130 evaluable patients who have completed consolidation (HD-CAV, 65; CAV-VP, 65), an additional 22 patients achieved CR (HD-CAV, 12; CAV-VP, 10) for an overall CR rate of 24%. Median duration of remission was 33.6 weeks for HD-CAV and 35.6 weeks for CAV-VP (P = 0.61). Median duration of complete response for HD-CAV was 33.8 weeks and for CAV-VP 36.7 weeks (P = 0.81). Survival curves were similar for the two regimens, with medians of 42.1 weeks for HD-CAV and 42.3 weeks for CAV-VP (P = 0.35). Survival correlated with performance status and quality of response. As anticipated, the major toxicity for both induction regimens was leukopenia. During induction, granulocyte nadirs of less than 500/mm3 occurred in 81% of patients on HD-CAV and 77% of patients on CAV-VP. Thus, dose intensification appears to produce high response rates and modest complete response rates in extensive SCLC, but it does not appear to improve materially survival compared to prior reports of conventional-dose therapy.
1979年4月至1981年11月，293例小细胞肺癌（SCLC）患者进入一项随机对照研究，比较两种诱导方案：大剂量CAV（HD-CAV）（环磷酰胺[CTX]1200mg/m²、阿霉素[ADR]70mg/m²和长春新碱[VCR]1mg/m²，于第1天和第21天静脉注射[IV]）与传统剂量CAV + VP-16（依托泊苷）（CAV-VP）（CTX 1000mg/m²、ADR 40mg/m²、VCR 1mg/m²，于第1天和第21天静脉注射，VP-16 100mg/m²于第1 - 3天和第21 - 23天静脉注射）。缓解和病情稳定的患者继续接受传统剂量CAV进行5个巩固疗程。对缓解者在第一个巩固疗程后进行预防性脑照射为可选方案。若患者患有广泛期疾病（即超过一侧胸腔）、未曾接受过化疗或放疗且体能状态为50或以上，则纳入本研究。经过2个诱导疗程后，215例患者可进行评估。其中，接受HD-CAV治疗的106例患者中有76例（72%）有反应（缓解率大于50%），包括13例完全缓解者（CR）；而接受CAV-VP治疗的108例患者中有80例（74%）有反应，包括15例CR。在完成巩固治疗的130例可评估患者中（HD-CAV组65例；CAV-VP组65例），又有22例患者实现CR（HD-CAV组12例；CAV-VP组10例），总CR率为24%。HD-CAV组的中位缓解持续时间为33.6周，CAV-VP组为35.6周（P = 0.61）。HD-CAV组的中位完全缓解持续时间为33.8周，CAV-VP组为36.7周（P = 0.81）。两种方案的生存曲线相似，HD-CAV组的中位生存期为42.1周，CAV-VP组为42.3周（P = 0.35）。生存与体能状态和缓解质量相关。正如预期的那样，两种诱导方案的主要毒性均为白细胞减少。在诱导期间，HD-CAV组81%的患者中性粒细胞最低点低于500/mm³，CAV-VP组77%的患者如此。因此，剂量强化似乎在广泛期SCLC中产生高反应率和适度的完全缓解率，但与先前传统剂量治疗的报告相比，似乎并未实质性地改善生存。
