Hochberg F, Prados M, Russell C, Weissman D, Evans R, Cook P, Burton G, Eisenberg P D, Valenzuela R, Verkh L
Massachusetts General Hospital, Boston, USA.
J Neurooncol. 1997 Mar;32(1):45-55. doi: 10.1023/a:1005727204169.
To evaluate the toxicity and response rate following BCNU with oxygen inhalation and escalating dosages of fluosol administered to patients with radiographic progression of malignant glioma after definitive surgery and radiotherapy.
This single arm, phase I-II multicenter trial, enrolled 99 patients with malignant gliomas recurrent after definitive surgery and radiotherapy. All patients received a fixed dose (200 mg/m2) of BCNU along with 100% oxygen and fluosol, a perfluorochemical. Fluosol doses were escalated between patients (150, 275, 400 and 600 ml/m2). Treatment was repeated every 6 weeks for a maximum of 6 cycles. Patients were assessed for toxicity at the time of infusion and sequentially thereafter. Response was evaluated clinically and radiologically at least every 6 weeks.
Treatment was well tolerated. Dose reductions were required at least once in 18 patients, treatment delays were necessary at least once in 33 patients. Grade 3-4 leukopenia occurred in 6 patients (12 events), grade 3-4 thrombocytopenia in 10 patients (25 events) and grade 3-4 liver enzymes elevations in 18 patients (31 events). Higher fluosol dosages did not produce increases in toxicity or responses. Response or stabilization was seen in 57% (38% were stabilizations) of the patients who entered the trial with progressive disease. The median time to progression was 45 weeks, and median survival was 66 weeks for patients who had response or stabilization. For patients with glioblastoma response/stabilization was seen in 45% with a mean duration of 24 weeks, for patients with anaplastic astrocytoma response/stabilization was seen in 68% with a mean duration of 50 weeks.
This treatment regimen is well tolerated. Our results suggest fluosol may enhance the effectiveness of BCNU for the treatment of recurrent malignant gliomas. Future studies will be performed using fluosol at the dose of 400 ml/m2.
评估在恶性胶质瘤患者接受根治性手术和放疗后出现影像学进展时，给予卡莫司汀（BCNU）联合吸氧以及递增剂量氟碳化合物（氟索）后的毒性和缓解率。
本单臂I-II期多中心试验纳入了99例根治性手术和放疗后复发的恶性胶质瘤患者。所有患者均接受固定剂量（200mg/m²）的卡莫司汀，同时吸入100%氧气并使用氟索（一种全氟化合物）。患者之间氟索剂量递增（150、275、400和600ml/m²）。每6周重复治疗一次，最多进行6个周期。在输注时及之后依次评估患者的毒性。至少每6周进行一次临床和影像学缓解评估。
治疗耐受性良好。18例患者至少需要一次剂量减少，33例患者至少需要一次治疗延迟。6例患者（12次事件）出现3-4级白细胞减少，10例患者（25次事件）出现3-4级血小板减少，18例患者（31次事件）出现3-4级肝酶升高。更高剂量的氟索并未导致毒性增加或缓解率提高。在入组时病情进展的患者中，57%（38%为病情稳定）出现缓解或病情稳定。进展的中位时间为45周，出现缓解或病情稳定的患者中位生存期为66周。对于胶质母细胞瘤患者，45%出现缓解/病情稳定，平均持续时间为24周；对于间变性星形细胞瘤患者，68%出现缓解/病情稳定，平均持续时间为50周。
该治疗方案耐受性良好。我们的结果表明氟索可能增强卡莫司汀治疗复发性恶性胶质瘤的有效性。未来将使用400ml/m²剂量的氟索进行研究。
