Papadimitrakopoulou V A, Dimery I W, Lee J J, Perez C, Hong W K, Lippman S M
University of Texas M.D. Anderson Cancer Center Department of Thoracic/Head and Neck Medical Oncology, Houston 77030-4095, USA.
Cancer J Sci Am. 1997 Mar-Apr;3(2):92-9.
To determine the efficacy of the combination of cisplatin, fluorouracil, and high-dose l-leucovorin (PFL) as organ-preserving induction therapy followed by radiotherapy in untreated patients with advanced squamous cell carcinoma of the head and neck.
This was a phase II study of PFL in 47 patients with resectable stage III (n = 20) and IV (n = 27) M0 squamous cell carcinoma of the head and neck, including larynx (n = 20), hypopharynx (n = 14), and oropharynx (n = 13). The PFL regimen consisted of cisplatin 25 mg/m2 on days 1 through 5, fluorouracil 800 mg/m2 CI on days 2 through 6, and l-leucovorin 250 mg/m2 on days 1 through 6, all by continuous intravenous infusion every 21 to 28 days for three courses. The primary study endpoint was initial response to and local disease control rate with PFL as induction chemotherapy, with an aim to confirm the previously reported complete response rate of 60% to 70%.
Of 47 patients enrolled, 46 were evaluable for response to PFL, 14 (30%) achieved a complete response, and 25 (54%) achieved a partial response, for an overall response rate of 84%. Of 39 patients evaluable for response after radiation therapy, 27 (69%) achieved a complete response and 11 (28%) a partial response. Local disease control was achieved in 37 of 46 (80%). Grade 3 or 4 toxic effects occurred frequently, with neutropenia in 27 (59%) of 46 evaluable patients, thrombocytopenia in 30%, mucositis in 41%, diarrhea in 13%, and nausea/ vomiting in 13%, but there were no treatment-related deaths. With a median follow-up of 35 months there have been nine recurrences (four local/regional and five distant) and 17 deaths (12 in patients with disease progression and five not directly related to the primary tumor). Second primary tumors have developed in six patients. At 3 years 62% of the patients remain alive with no disease progression, and the 3-year survival estimate with preserved organ function is 66%.
PFL induction chemotherapy produced only a modest complete response rate, possibly due to suboptimal dose intensity, and was associated with substantial, although not life-threatening, toxicity. Newer regimens and treatment modalities are still needed in the management of advanced squamous cell carcinoma of the head and neck.
确定顺铂、氟尿嘧啶和高剂量左亚叶酸（PFL）联合方案作为保器官诱导治疗，随后进行放疗，用于未经治疗的晚期头颈部鳞状细胞癌患者的疗效。
这是一项关于PFL的II期研究，入组了47例可切除的III期（n = 20）和IV期（n = 27）M0头颈部鳞状细胞癌患者，包括喉癌（n = 20）、下咽癌（n = 14）和口咽癌（n = 13）。PFL方案包括第1至5天顺铂25mg/m²、第2至6天氟尿嘧啶800mg/m²持续静脉输注、第1至6天左亚叶酸250mg/m²，每21至28天为一个疗程，共三个疗程。主要研究终点是PFL作为诱导化疗的初始反应和局部疾病控制率，旨在确认先前报道的60%至70%的完全缓解率。
47例入组患者中，46例可评估对PFL的反应，14例（30%）达到完全缓解，25例（54%）达到部分缓解，总缓解率为84%。39例可评估放疗后反应的患者中，27例（69%）达到完全缓解，11例（28%）达到部分缓解。46例中有37例（80%）实现了局部疾病控制。3或4级毒性反应频繁发生，46例可评估患者中有27例（59%）出现中性粒细胞减少，30%出现血小板减少，41%出现黏膜炎，13%出现腹泻，13%出现恶心/呕吐，但无治疗相关死亡。中位随访35个月，有9例复发（4例局部/区域复发和5例远处复发）和17例死亡（12例因疾病进展，5例与原发肿瘤无直接关系）。6例患者发生了第二原发性肿瘤。3年时，62%的患者无疾病进展存活，保留器官功能的3年生存率估计为66%。
PFL诱导化疗的完全缓解率仅为中等程度，可能是由于剂量强度欠佳，且伴有严重但不危及生命的毒性。在晚期头颈部鳞状细胞癌的治疗中仍需要更新的方案和治疗模式。
