Cobo-Dols M, Gil-Calle S, Villar-Chamorro E, Alés-Díaz I, Carabantes-Ocón F, Alcalde-García J, Gutiérrez-Calderón V, Montesa-Pino A, Bretón-García J J, Benavides-Orgaz M
Medical Oncology Section, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
Clin Transl Oncol. 2006 Jul;8(7):519-24. doi: 10.1007/s12094-006-0052-6.
In this Phase I/II trial, the maximumtolerated dose (MTD) and activity of cisplatin plus vinorelbine (VRL) administered in continuous infusion as first-line treatment of advanced non small cell lung cancer (NSCLC) was determined in 12 consecutive chemotherapy-naive patients with advanced NSCLC.
The dose of cisplatin was 100 mg/m(2) in all patients, and vinorelbine was administered as an initial intravenous (iv) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous iv infusion at 4 different 24 h dose levels (DLs) to be repeated every 21 days. All 12 patients (47 cycles) were evaluable for response and toxicity.
The MTD was 8 mg/m(2) bolus followed by a continuous iv infusion of 8 mg/m(2) per day over 4 days. The dose limiting toxicities (DLT) were febrile neutropenia in 4 patients and grade 3 mucositis in 1 patient. There was less neuro-toxicity and compared to the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Partial responses were observed in 6 patients; an overall response rate of 50% (95% CI: 30-65%). Median time to progression was 5,5 months (95% CI: 1,5-11 months) and median survival was 11 months (95% CI: 5-20 months).
The results demonstrate that, in this setting of first-line treatment of NSCLC, cisplatin plus vinorelbine at 8 mg/m(2) bolus followed by a continuous infusion of 8 mg/m(2) per day over 4 days is the recommended schedule. Further trials would be useful to establish activity of this combination.
在这项I/II期试验中，对12例初治的晚期非小细胞肺癌（NSCLC）患者连续给予顺铂加长春瑞滨（VRL）持续静脉输注作为一线治疗，确定其最大耐受剂量（MTD）和活性。
所有患者顺铂剂量为100mg/m²，长春瑞滨于第1天静脉推注8mg/m²作为初始剂量，随后在4个不同的24小时剂量水平（DLs）进行4天持续静脉输注，每21天重复一次。所有12例患者（47个周期）均可评估疗效和毒性。
MTD为静脉推注8mg/m²，随后4天每天持续静脉输注8mg/m²。剂量限制性毒性（DLT）为4例患者出现发热性中性粒细胞减少，1例患者出现3级黏膜炎。与每周推注方案相比，神经毒性较小。3个周期后无明显累积毒性。6例患者观察到部分缓解；总缓解率为50%（95%CI：30 - 65%）。中位疾病进展时间为5.5个月（95%CI：1.5 - 11个月），中位生存期为11个月（95%CI：5 - 20个月）。
结果表明，在NSCLC一线治疗中，推荐的方案是顺铂加长春瑞滨，静脉推注8mg/m²，随后4天每天持续静脉输注8mg/m²。进一步的试验对于确定该联合方案的活性将是有用的。
