Hasbini A, Mahjoubi R, Fandi A, Chouaki N, Taamma A, Lianes P, Cortès-Funes H, Alonso S, Armand J P, Cvitkovic E, Raymond E
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Ann Oncol. 1999 Apr;10(4):421-5. doi: 10.1023/a:1008342828496.
This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT).
Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria.
Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity.
Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months.
The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.
本II期研究旨在探讨在常规蒽环类药物-顺铂和5-氟尿嘧啶为基础的化疗方案中加入丝裂霉素对复发和转移性鼻咽型未分化癌（UCNT）的潜在益处。
1989年7月至1991年12月，44例连续的复发或转移性UCNT患者（男/女36/8；中位年龄：45岁，范围20 - 72岁；体能状态（PS）0：20例患者，PS 1：14例患者，PS 2：10例患者）在完成临床、生物学和放射学的治疗前检查后进入本研究。化疗（FMEP方案）包括第1天至第4天持续输注800mg/m²/天的5-氟尿嘧啶，联合第1天给予70mg/m²表柔比星、10mg/m²丝裂霉素和100mg/m²顺铂，每四周进行六个周期。丝裂霉素仅在第1、3和5周期使用。11例患者为孤立性局部复发，12例患者为局部复发伴远处转移，21例患者仅有转移。根据世界卫生组织标准评估毒性和反应。
在212个可评估周期中的122个（57%）以及44例患者中的39例（89%）观察到3 - 4级中性粒细胞减少；16例患者（36%）和24个周期（11.3%）出现发热性中性粒细胞减少。27例患者（61%）和45个周期（21%）观察到3 - 4级血小板减少，其中45个周期中的27个（60%）与丝裂霉素有关。18例患者（40%）和23个周期（11%）出现3级贫血，其中23个周期中的18个（78%）与丝裂霉素有关。25个周期（11%）和14例患者（32%）出现3 - 4级粘膜炎，主要发生在先前接受过头颈部放疗的患者中。有4例治疗相关死亡（9%）；其中3例与中性粒细胞减少相关，1例与心脏毒性相关。
44例患者可评估反应：44例中有23例客观反应（52%），包括6例完全缓解（13%）和17例部分缓解（38%）。在记录到反应后，13例患者接受了额外的放疗：鼻咽肿瘤 + 颈部淋巴结（8例患者）和/或骨转移部位（5例患者）；纵隔淋巴结（1例患者）。中位随访87个月（范围71 - 100个月），5例患者存活且持续完全缓解。中位生存时间为14个月，中位进展时间为9个月。
所研究的方案对复发/转移性UCNT有效，但毒性过大。
