Dreyfuss A I, Clark J R, Wright J E, Norris C M, Busse P M, Lucarini J W, Fallon B G, Casey D, Andersen J W, Klein R
Dana-Faber Cancer Institute, Boston, Massachusetts.
Ann Intern Med. 1990 Feb 1;112(3):167-72. doi: 10.7326/0003-4819-112-3-167.
To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck.
Nonrandomized, prospective trial.
A comprehensive cancer center.
Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity.
Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy.
A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L.
Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.
研究持续输注顺铂、5-氟尿嘧啶和高剂量亚叶酸钙（PFL）作为诱导化疗方案，用于治疗既往未经治疗的晚期头颈部鳞状细胞癌患者的疗效。
非随机前瞻性试验。
一家综合癌症中心。
35例患者（Ⅲ期4例[11%]；Ⅳ期[M0]31例[89%]），所有患者均对疗效和毒性可进行评估。
在确定性局部区域治疗（手术和放疗或单纯放疗）前进行2至3个周期的PFL化疗。化疗包括顺铂持续静脉输注（25mg/m²体表面积，第1至5天）；5-氟尿嘧啶（800mg/m²体表面积，第2至6天）；亚叶酸钙（500mg/m²体表面积，第1至6天），每28天重复一次。通过手术切除或活检评估病理反应。在化疗开始前及开始后18小时测定血清亚叶酸水平。
35例患者中有28例（80%）对PFL化疗有临床反应：23例（66%）患者完全缓解（90%CI，50%至79%），5例（14%）患者部分缓解。19例患者中有14例（74%）经病理证实完全缓解。最常见的毒性反应是黏膜炎（2至3级；94%的患者）。11例（31%）患者因毒性反应需要降低剂量。无治疗相关死亡病例。对7例患者测定了亚叶酸钙和（6S）5-甲基四氢叶酸的血清水平。18小时后，亚叶酸钙的平均水平（±标准差）为34.3±1.5μmol/L，其中只有8.0±0.5%是活性6S异构体。血清（6S）5-甲基四氢叶酸的平均水平为9.2±0.6μmol/L。
持续输注顺铂、5-氟尿嘧啶和高剂量亚叶酸钙是一种新的、高活性的化疗方案，可使相当比例的晚期局部区域头颈部鳞状细胞癌患者获得临床及病理证实的完全缓解。需要进一步研究以证实PFL方案的活性，并确定其对局部肿瘤控制、无病生存期和总生存期的潜在影响。
