Miller V A, Rigas J R, Pisters K M, Grant S C, Pfister D G, Heelan R T, Kris M G
Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Am J Clin Oncol. 1995 Aug;18(4):303-6. doi: 10.1097/00000421-199508000-00007.
This study determined the maximum tolerated dose (MTD) of ifosfamide that could be given with high-dose cisplatin to non-small cell lung cancer (NSCLC) patients previously treated with non-platin-containing chemotherapy and to assess the efficacy of this combination. Twenty-three patients with inoperable NSCLC treated with one prior chemotherapy regimen received continuous infusion ifosfamide 1.2 g/m2 per day with MESNA for 5 days every 35 days and cisplatin 120 mg/m2. After one patient who received cisplatin as a single dose developed grade 4 nephrotoxicity and myelosuppression, cisplatin was given in four divided doses (30 mg/m2 per day) and the ifosfamide dose was lowered to 1.0 g/m2 per day, infused over 4 days. Dose-limiting grades 3 and 4 leukopenia was seen in 43%. A major objective response rate of 9% was observed. The 1-year survival was 30%, with a median survival of 6.4 months. The MTD of ifosfamide administered with cisplatin (30 mg/m2 per day for 4 consecutive days) to this population of patients is 1.0 g/m2 daily for 4 days. This combination produced limited anticancer activity and significant toxicity. Excessive toxicity was observed when cisplatin was given as a single dose with ifosfamide, and this schedule should not be used.
本研究确定了异环磷酰胺与大剂量顺铂联合应用于先前接受过不含铂化疗的非小细胞肺癌（NSCLC）患者时的最大耐受剂量（MTD），并评估了该联合方案的疗效。23例接受过一种先前化疗方案治疗的无法手术的NSCLC患者，每35天接受5天的连续静脉输注异环磷酰胺1.2 g/m²/天并加用美司钠，以及顺铂120 mg/m²。在1例接受单次剂量顺铂治疗的患者出现4级肾毒性和骨髓抑制后，顺铂改为分4次给药（30 mg/m²/天），异环磷酰胺剂量降至1.0 g/m²/天，输注4天。43%的患者出现了3级和4级剂量限制性白细胞减少。观察到主要客观缓解率为9%。1年生存率为30%，中位生存期为6.4个月。对于该组患者，异环磷酰胺与顺铂（连续4天每天30 mg/m²）联合应用时的MTD为每天1.0 g/m²，共4天。该联合方案产生的抗癌活性有限且毒性显著。当顺铂与异环磷酰胺单次给药时观察到过度毒性，不应采用该给药方案。
