Lynch T J, Clark J R, Kalish L A, Fallon B G, Elias A D, Skarin A, Frei E
Division of Clinical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215.
Cancer. 1992 Oct 1;70(7):1880-5. doi: 10.1002/1097-0142(19921001)70:7<1880::aid-cncr2820700713>3.0.co;2-3.
Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC:
Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen).
Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2.
PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy.
顺铂和5-氟尿嘧啶在临床前系统中已显示出协同作用。作者将甲氨蝶呤与静脉输注顺铂和5-氟尿嘧啶联合使用,试图制定一种在晚期非小细胞肺癌中具有更高活性的治疗方案:
26例先前未接受过治疗的非小细胞肺癌门诊患者接受持续静脉输注顺铂(25mg/m²/天,共5天)、5-氟尿嘧啶(800mg/m²/天,共5天)和中剂量甲氨蝶呤(在第15天、第22天给予200mg/m²),随后进行亚叶酸解救(PFM方案)。
患者接受的中位治疗周期数为4个。2例患者完全缓解,10例部分缓解(总缓解率为46.2%,即26例中的12例)。治疗失败的中位时间为22.5周;从化疗开始计算的中位生存期为55周。没有因化疗导致的毒性死亡。血小板减少是唯一的4级毒性(27%)。26例患者中有17例(66%)发生1/4级和2/4级周围神经病变,且与顺铂累积剂量超过300mg/m²有关。
PFM方案(使用持续静脉输注顺铂)产生了较高的缓解率,但导致低级周围神经病变的发生率较高。