Chua Susan L, Rosenthal Mark A, Wong Shirley S, Ashley David M, Woods Anne-Marie, Dowling Anthony, Cher Lawrence M
Centre for Developmental Cancer Therapeutics, Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Neuro Oncol. 2004 Jan;6(1):38-43. doi: 10.1215/S1152851703000188.
Temozolomide has established activity in the treatment of recurrent glioblastoma multiforme (GBM). Caelyx (liposomal doxorubicin) has established activity in a broad range of tumors but has not been extensively evaluated in the treatment of GBM. Phase 1 data suggest that temozolomide and Caelyx can be combined safely at full dose. In this phase 2 study, combination temozolomide (200 mg/m(2) orally, days 1-5) and Caelyx (40 mg/m(2) i.v., day 1) was given every 4 weeks to a cohort of 22 patients with recurrent GBM, who received a total of 109 cycles (median 3.5 cycles). The median age of the patients was 55 years (range, 31-80 years), and 17 were male. All patients had received radiotherapy, but only 2 had received prior chemotherapy. One patient (5%) had a complete response, 3 patients (14%) had a partial response, and 11 patients (50%) had stable disease. The median time to progression for the cohort was 3.2 months (range, 1-13 months). Median overall survival was 8.2 months (range, 1-16+ months). Seven patients (32%) were progression free at 6 months. Hematological toxicity included grade 3/4 neutropenia in 4 patients (18%) and grade 3/4 thrombocytopenia in 4 patients (18%). Grade 3 non-hematologic toxicity included rash in 3 patients (14%), nausea and vomiting in 1 patient (4%), hypersensitivity reaction to Caelyx in 3 patients (14%), and palmar-plantar toxicity in 1 patient (4%). We conclude that the combination of temozolomide and Caelyx is well tolerated, results in a modest objective response rate, but has encouraging disease stabilization in the treatment of recurrent GBM.
替莫唑胺已被证实对复发性多形性胶质母细胞瘤（GBM）有治疗活性。凯莱英（脂质体阿霉素）对多种肿瘤有治疗活性，但尚未在GBM治疗中得到广泛评估。1期数据表明替莫唑胺和凯莱英可以全剂量安全联合使用。在这项2期研究中，对22例复发性GBM患者每4周给予替莫唑胺（口服200mg/m²，第1 - 5天）和凯莱英（静脉注射40mg/m²，第1天）联合治疗，这些患者共接受了109个周期（中位周期数3.5个）。患者的中位年龄为55岁（范围31 - 80岁），其中17例为男性。所有患者均接受过放疗，但只有2例接受过先前的化疗。1例患者（5%）完全缓解，3例患者（14%）部分缓解，11例患者（50%）病情稳定。该队列的中位进展时间为3.2个月（范围1 - 13个月）。中位总生存期为8.2个月（范围1 - 16 +个月）。7例患者（32%）在6个月时无进展。血液学毒性包括4例患者（18%）出现3/4级中性粒细胞减少和4例患者（18%）出现3/4级血小板减少。3级非血液学毒性包括3例患者（14%）出现皮疹，1例患者（4%）出现恶心和呕吐，3例患者（14%）对凯莱英出现过敏反应，1例患者（4%）出现手足毒性。我们得出结论，替莫唑胺和凯莱英联合使用耐受性良好，客观缓解率适中，但在复发性GBM治疗中疾病稳定情况令人鼓舞。
