Maluf F C, Leiser A L, Aghajanian C, Sabbatini P, Pezzulli S, Chi D S, Wolf J K, Levenback C, Loh E, Spriggs D R
Developmental Chemotherapy Service and Gynecologic Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Int J Gynecol Cancer. 2006 May-Jun;16(3):1165-71. doi: 10.1111/j.1525-1438.2006.00454.x.
The aim of this study was to evaluate the activity and toxicity of a tirapazamine (TPZ)/cisplatin drug combination in patients with stage IV or recurrent cervical cancer. The chemotherapy was administered for a maximum of eight cycles every 21 days. TPZ was administered intravenously at 330 mg/m(2) over a 2-h infusion, followed 1 h later by cisplatin intravenously at 75 mg/m(2) over 1 h on day 1. All patients received antiemetics including dexamethasone, ondansetron, and lorazepam. Subsequent doses were unchanged, reduced, or omitted according to observed toxicity and protocol guidelines. Response evaluation was performed every two cycles. Thirty-six patients with stage IV or recurrent cervical cancer were treated. Ninety-four percent of patients had prior radiotherapy. Two patients had prior chemotherapy. There were two complete responses and eight partial responses (27.8%). An additional 11 patients (30.6%) had stable disease as their best response. Response rate was greater in tumors outside of the previously radiated field (44.4% vs 11.1%). The median time to progression was 32.7 weeks. The most frequent grade 3 or 4 adverse events were nausea, vomiting, and fatigue, which occurred in 30.6%, 25%, and 22% of subjects, respectively. Anemia was the most frequent grade 3 or 4 hematologic toxicity at 8.3%. We conclude that the combination of cisplatin and TPZ was reasonably well tolerated in patients with recurrent or advanced cervical cancer. Further evaluation of this drug combination may be warranted.
本研究旨在评估替拉扎明（TPZ）/顺铂联合用药对IV期或复发性宫颈癌患者的活性和毒性。化疗每21天进行，最多8个周期。TPZ以330mg/m²静脉滴注2小时，1小时后在第1天静脉滴注顺铂75mg/m²，持续1小时。所有患者均接受包括地塞米松、昂丹司琼和劳拉西泮在内的止吐药。后续剂量根据观察到的毒性和方案指南不变、减少或省略。每两个周期进行一次疗效评估。36例IV期或复发性宫颈癌患者接受了治疗。94%的患者曾接受过放疗。2例患者曾接受过化疗。有2例完全缓解和8例部分缓解（27.8%）。另外11例患者（30.6%）病情稳定，为最佳反应。先前放疗区域外的肿瘤缓解率更高（44.4%对11.1%）。中位进展时间为32.7周。最常见的3级或4级不良事件是恶心、呕吐和疲劳，分别发生在30.6%、25%和22%的受试者中。贫血是最常见的3级或4级血液学毒性，发生率为8.3%。我们得出结论，顺铂和TPZ联合用药在复发性或晚期宫颈癌患者中耐受性较好。可能有必要对这种联合用药进行进一步评估。
