Pfister D G, Bajorin D, Motzer R, Scher H, Louison C, Harrison L, Shah J, Strong E, Bosl G
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
Arch Otolaryngol Head Neck Surg. 1994 Jan;120(1):89-95. doi: 10.1001/archotol.1994.01880250077011.
To evaluate the activity and toxicity of the drug combination cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin calcium (PFL) as induction chemotherapy in patients with advanced and untreated squamous cell head and neck (SCHN) cancer.
Nonrandomized, prospective trial.
Referral center (comprehensive cancer center).
Twenty-two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment would have required total laryngectomy.
Three cycles of PFL were administered prior to local-regional therapy (concomitant cisplatin and radiation and/or neck dissection, with total laryngectomy reserved for nonresponse or relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL combination was administered every 21 days.
Clinical response to chemotherapy and observed toxic effects during chemotherapy.
Five patients were inevaluable for response, with three early deaths (infection in two and sudden death in one), one cerebrovascular accident, and one patient declining further chemotherapy. Of the remaining 17 patients, 10 had a major response to chemotherapy, but in only five patients (29%) was this complete (95% confidence interval, 8% to 51%). Other significant toxic effects included grade 3 to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10.
While PFL is active in patients with SCHN cancer, we were unable to reproduce the high complete response rates reported by other centers. Its use can be associated with significant toxic effects. We do not recommend the use of PFL for the treatment of patients with SCHN cancer outside the context of a clinical trial until there is further critical assessment of its activity and toxicity.
评估顺铂、持续输注氟尿嘧啶和大剂量口服亚叶酸钙（PFL）联合用药作为晚期未治疗的头颈部鳞状细胞癌（SCHN）患者诱导化疗的活性和毒性。
非随机前瞻性试验。
转诊中心（综合癌症中心）。
22例III期（n = 7）和IV期（n = 15）M0的SCHN癌症患者，其中喉癌（n = 13）、下咽癌（n = 7）和口咽癌（n = 2），其标准治疗本需全喉切除术。
在局部区域治疗（顺铂同步放疗和/或颈部清扫术，全喉切除术留待无反应或复发时进行）之前给予三个周期的PFL。化疗包括第1天短时间静脉输注顺铂（100 mg/m²）；第1至5天持续输注氟尿嘧啶（800 mg/m²）；每4小时口服亚叶酸（100 mg），共30剂。PFL联合用药每21天进行一次。
化疗的临床反应及化疗期间观察到的毒性作用。
5例患者无法评估反应情况，其中3例早期死亡（2例死于感染，1例猝死），1例发生脑血管意外，1例患者拒绝进一步化疗。其余17例患者中，10例对化疗有主要反应，但仅5例（29%）完全缓解（95%置信区间，8%至51%）。其他显著的毒性作用包括8例3至4级黏膜炎和10例3至4级中性粒细胞减少。
虽然PFL对SCHN癌症患者有活性，但我们未能重现其他中心报道的高完全缓解率。其使用可能伴有显著的毒性作用。在对其活性和毒性进行进一步严格评估之前，我们不建议在临床试验之外使用PFL治疗SCHN癌症患者。
