Lin J C, Jan J S, Hsu C Y
Department of Radiation Oncology, Taichung Veterans General Hospital, School of Medicine, China Medical College, Taiwan.
Cancer. 1998 Aug 15;83(4):635-40. doi: 10.1002/(sici)1097-0142(19980815)83:4<635::aid-cncr2>3.0.co;2-j.
Distant metastasis is a more common pattern of failure than locoregional recurrence after adequate radiotherapy in patients with nasopharyngeal carcinoma (NPC). The objective of this Phase II study was to assess the efficacy and toxicity of weekly chemotherapy in NPC patients with distant metastasis.
Patients with a histologic diagnosis of NPC and documented distant metastasis were eligible, including those who 1) had metastatic disease at presentation; 2) had developed metastatic disease during or at any time after local radiotherapy; or 3) had developed progressive disease or recurrence of metastasis after prior chemotherapy. The weekly chemotherapy regimen was comprised of 5-fluorouracil (5-FU), 1250 mg/m2, plus cisplatin, 25 mg/m2, as a 24-hour continuous intravenous infusion via a subcutaneous implanted port, using an ambulatory pump in an outpatient setting for the first 19 patients. Because of the low incidence and reduced severity of toxicity, the dosage of chemotherapy was escalated to 5-FU, 1667 mg/m2, plus cisplatin, 33.3 mg/m2, for the subsequent 25 patients.
Between October 1992 and June 1996, a total of 44 patients with metastatic NPC were studied. They were 36 males and 8 females with a median age of 48 years (range, 30-72 years). Poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic types. Twenty-six patients had single organ metastasis, whereas 18 patients had multiple organ involvement. Locoregional disease existed simultaneously in 16 patients. The majority of patients had received previous radiotherapy (33 patients) and chemotherapy (23 patients: 16 as concurrent therapy for localized disease, 6 as salvage therapy for metastatic disease, and 1 for a postradiation adjuvant purpose). Among 38 patients with measurable disease, 8 obtained a complete response (CR) (21.1%), 12 obtained a partial response (PR) (31.6%), 17 had stable disease (SD) (44.7%), and 1 had progressive disease (2.6%). The median duration of CR, PR, and SD were 6.5 months, (range, 2-12 months), 5.5 months (range, 2-9 months), and 2.5 months (range, 1-6 months), respectively. Toxicity was found to be very mild. Only one patient developed a World Health Organization (WHO) Grade 1 mucositis. No visible alopecia and no treatment-related deaths occurred. WHO Grade 3-4 hematologic toxicities occurred in 1.0% of patients for leukopenia, 4.1% for anemia, and 2.9% for thrombocytopenia.
Data from the current study indicate that 24-hour weekly infusion of 5-FU plus cisplatin has moderate activity but very low toxicity for NPC patients with distant metastasis. Further study is necessary to find more effective therapy.
远处转移是鼻咽癌（NPC）患者在接受充分放疗后比局部区域复发更常见的失败模式。本II期研究的目的是评估每周化疗对远处转移的NPC患者的疗效和毒性。
组织学诊断为NPC且有远处转移记录的患者符合条件，包括那些1）初诊时已有转移性疾病；2）在局部放疗期间或之后任何时间出现转移性疾病；或3）在先前化疗后出现疾病进展或转移复发的患者。每周化疗方案包括5-氟尿嘧啶（5-FU），1250mg/m²，加顺铂，25mg/m²，通过皮下植入端口进行24小时持续静脉输注，前19例患者在门诊使用便携式泵。由于毒性发生率低且严重程度降低，后续25例患者的化疗剂量增加至5-FU，1667mg/m²，加顺铂，33.3mg/m²。
1992年10月至1996年6月，共研究了44例转移性NPC患者。他们中男性36例，女性8例，中位年龄48岁（范围30-72岁）。低分化表皮样癌或未分化癌是主要病理类型。26例患者有单个器官转移，而18例患者有多器官受累。16例患者同时存在局部区域疾病。大多数患者曾接受过放疗（33例）和化疗（23例：16例作为局部疾病的同步治疗，6例作为转移性疾病的挽救治疗，1例作为放疗后辅助治疗）。在38例可测量疾病的患者中，8例获得完全缓解（CR）（21.1%），12例获得部分缓解（PR）（31.6%），17例病情稳定（SD）（44.7%），1例病情进展（2.6%）。CR、PR和SD的中位持续时间分别为6.5个月（范围2-12个月）、5.5个月（范围2-9个月）和2.5个月（范围1-6个月）。发现毒性非常轻微。只有1例患者出现世界卫生组织（WHO）1级黏膜炎。未出现明显脱发，也未发生与治疗相关的死亡。WHO 3-4级血液学毒性在白细胞减少患者中发生率为1.0%，贫血患者中为4.1%，血小板减少患者中为2.9%。
本研究数据表明，对于远处转移的NPC患者，每周24小时输注5-FU加顺铂具有中等活性但毒性非常低。有必要进一步研究以找到更有效的治疗方法。
