Bedikian A Y, Legha S S, Eton O, Buzaid A C, Papadopoulos N, Coates S, Simmons T, Neefe J, von Roemeling R
Department of Melanoma/Sarcoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, USA.
Ann Oncol. 1997 Apr;8(4):363-7. doi: 10.1023/a:1008249232000.
A phase II study was undertaken to determine the efficacy of tirapazamine (TPZ) combined with cisplatin (cDDP) in patients with metastatic melanoma.
Between June 1994 and November 1995, 48 patients with metastatic melanoma were treated with TPZ (260 mg/m2, administered intravenously over two hours) followed in one-hour by cDDP (75 mg/m2 over one hour) every 21 days. Sixteen patients had received prior chemotherapy, and 13 of these had failed to respond to prior cDDP. None of the patients had symptomatic brain metastasis.
Nine patients had partial responses, with an overall response rate of 19% (95% confidence interval (95% CI) of 9%-33%). The median duration of response was six months. None of the responders had received prior chemotherapy. Responses were seen in 8 (33%, confidence interval of 16%-55%) of 24 patients with primary cutaneous melanoma who had received no prior chemotherapy and in the only patient with previously untreated conjunctival melanoma. There were no responders among the seven patients with choroidal melanoma and 16 patients with previously treated cutaneous melanoma. Two patients with partial responses were rendered free of gross disease surgically three months after completing eight courses of TPZ-cDDP; they remain free of tumor recurrence. Responses were seen in lymph nodes (27%), lung (26%), skin (20%), adrenal gland (20%), soft tissues (17%) and liver (17%). Common toxicities included muscle cramps, fatigue, gastrointestinal effects and peripheral neuropathy. Fatigue, nausea, vomiting, anorexia, and muscle cramps were grade 3 or 4 in less than 10% of the courses. Neutropenia and thrombocytopenia were rare.
The TPZ-cDDP combination has definite activity against chemotherapy-naïve patients with cutaneous melanoma and warrant further studies in combination with other cytotoxic agents.
开展一项II期研究，以确定替拉扎明（TPZ）联合顺铂（cDDP）治疗转移性黑色素瘤患者的疗效。
1994年6月至1995年11月期间，48例转移性黑色素瘤患者接受TPZ治疗（260mg/m²，静脉滴注2小时），1小时后接着每21天接受cDDP治疗（75mg/m²，静脉滴注1小时）。16例患者曾接受过化疗，其中13例对先前的cDDP治疗无反应。所有患者均无有症状的脑转移。
9例患者出现部分缓解，总缓解率为19%（95%置信区间（95%CI）为9%-33%）。缓解的中位持续时间为6个月。所有缓解者均未接受过先前的化疗。在24例未接受过先前化疗的原发性皮肤黑色素瘤患者中有8例（33%，置信区间为16%-55%）出现缓解，在唯一1例先前未治疗的结膜黑色素瘤患者中也出现了缓解。7例脉络膜黑色素瘤患者和16例先前接受过治疗的皮肤黑色素瘤患者中均无缓解者。2例部分缓解患者在完成8个疗程的TPZ-cDDP治疗3个月后通过手术实现无肉眼可见疾病；他们仍无肿瘤复发。在淋巴结（27%）、肺（26%）、皮肤（20%）、肾上腺（20%）、软组织（17%）和肝脏（17%）中均观察到缓解。常见毒性包括肌肉痉挛、疲劳、胃肠道反应和周围神经病变。疲劳、恶心、呕吐、厌食和肌肉痉挛在不到10%的疗程中为3级或4级。中性粒细胞减少和血小板减少很少见。
TPZ-cDDP联合方案对未接受过化疗的皮肤黑色素瘤患者有确切活性，值得与其他细胞毒性药物联合进行进一步研究。
