Samuels B L, Herndon J E, Harmon D C, Carey R, Aisner J, Corson J M, Suzuki Y, Green M R, Vogelzang N J
Lutheran General Hospital, Park Ridge, Illinois 60068, USA.
Cancer. 1998 Apr 15;82(8):1578-84.
In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro-5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population.
Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation.
Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers.
The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.
在先前一项针对晚期、未经治疗的间皮瘤患者的癌症与白血病B组（CALGB）II期试验中，二氢-5-氮杂胞苷（DHAC）显示出17%的缓解率，包括1例完全缓解，且仅有轻度骨髓抑制。本II期研究（CALGB 9031）旨在确定在同一患者群体中，顺铂与DHAC联合使用的有效性和毒性。
36例患者接受同步治疗，DHAC以1500 mg/m²/天持续输注5天，顺铂15 mg/m²/天，共5天。每3周重复一次治疗。如果毒性最小，后续周期顺铂剂量将增至20 mg/m²/天。治疗持续至疾病进展或毒性过大需要停药。
总体而言，在29例可评估患者中观察到5例客观缓解（客观缓解率为17%）。缓解持续时间中位数为6.6个月。中位生存期为6.4个月，临床失败的中位时间为2.7个月。主要毒性为明显的胸痛/心包痛，与单独使用DHAC时观察到的情况相同。分别在治疗第9天和第17天有2例不明原因的早期死亡。29%的患者出现明显的白细胞减少，但无中性粒细胞减少性发热。
对于间皮瘤患者，顺铂与DHAC联合使用并未比单独使用DHAC提高缓解率；然而，它确实增加了毒性，尤其是白细胞减少。不建议将这种联合方案用于涉及间皮瘤患者的进一步研究。
