Musolino Antonino, Perrone Maria Antonietta, Michiara Maria, Delnevo Daniela, Franciosi Vittorio, Di Blasio Beatrice, Ceci Guido, Camisa Roberta, Ardizzoni Andrea, Cocconi Giorgio
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Cancer. 2005 May 15;103(10):2109-17. doi: 10.1002/cncr.21024.
The current study was designed to assess the activity and safety of a novel combination therapy for patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL).
Forty-three consecutive patients with recurrent or refractory aggressive NHL were treated with lomustine (chloroethylnitrosourea [CCNU]; 60 mg/m2 on Day 1), ifosfamide (1.5 g/m(2 on Days 1, 2 and 21, 22), bleomycin (5 mg/m2 on Days 1, 5 and 21, 25), vincristine (1.4 mg/m2 on Days 1, 8 and 21, 28), and cisplatin (25 mg/m2 on Days 3, 4, 5 and 23, 24, 25), every 42 days (CIBO-P regimen).
Thirty-nine patients (91%) were evaluable for response. The median patient age was 63 years. Thirty-five percent of the patients had received > or = 2 lines of previous chemotherapy and 40% had elevated lactate dehydrogenase levels at the time of treatment initiation. The overall objective response rate was 77% (95% confidence interval [95% CI], 63-90%), including 19 (49%) complete (CR) and 11 (28%) partial responses. CIBO-P induced responses in primary refractory disease and in patients treated for second or subsequent disease recurrences. A CR with previous therapy was the most important factor associated with a significantly higher CR rate. The median duration of response was 6 months (95% CI, 4.4-7.7 months) and the median survival duration was 10.7 months (95% CI, 5.9-18.1 months). Five patients (11.6%) remained disease free for > or = 24 months. By multivariate analysis, a CR with previous therapy and average dose intensity of CIBO-P drugs were independent prognostic factors for time-to-treatment failure, whereas a CR with previous therapy and serum lactate dehydrogenase were independent predictors for survival. Myelosuppression was the most frequent serious complication of this regimen. However, none of the patients had hemorrhage with thrombocytopenia, and only 2 patients (5%) had febrile neutropenia.
In the current study, CIBO-P was a novel, highly active, and safe combination therapy for patients with refractory disease with a poor prognosis or for patients with multiply recurrent aggressive NHL.
本研究旨在评估一种新型联合疗法对复发或难治性侵袭性非霍奇金淋巴瘤(NHL)患者的活性和安全性。
43例连续的复发或难治性侵袭性NHL患者接受洛莫司汀(氯乙基亚硝脲[CCNU];第1天60mg/m²)、异环磷酰胺(第1、2、21、22天1.5g/m²)、博来霉素(第1、5、21、25天5mg/m²)、长春新碱(第1、8、21、28天1.4mg/m²)和顺铂(第3、4、5、23、24、25天25mg/m²)治疗,每42天重复(CIBO-P方案)。
39例患者(91%)可评估疗效。患者中位年龄为63岁。35%的患者既往接受过≥2线化疗,40%的患者在开始治疗时乳酸脱氢酶水平升高。总体客观缓解率为77%(95%置信区间[95%CI],63 - 90%),包括19例(49%)完全缓解(CR)和11例(28%)部分缓解。CIBO-P方案在原发性难治性疾病以及接受二线或后续疾病复发治疗的患者中均诱导出缓解。既往治疗达到CR是与显著更高CR率相关的最重要因素。中位缓解持续时间为6个月(95%CI,4.4 - 7.7个月),中位生存持续时间为10.7个月(95%CI,5.9 - 18.1个月)。5例患者(11.6%)无病生存≥24个月。多因素分析显示,既往治疗达到CR以及CIBO-P方案药物的平均剂量强度是治疗失败时间的独立预后因素,而既往治疗达到CR和血清乳酸脱氢酶是生存的独立预测因素。骨髓抑制是该方案最常见的严重并发症。然而,无一例患者出现血小板减少性出血,仅2例患者(5%)出现发热性中性粒细胞减少。
在本研究中,CIBO-P方案是一种针对预后不良的难治性疾病患者或多次复发的侵袭性NHL患者的新型、高活性且安全的联合疗法。