Schornagel J H, Verweij J, de Mulder P H, Cognetti F, Vermorken J B, Cappelaere P, Armand J P, Wildiers J, de Graeff A, Clavel M
Netherlands Cancer Institute, Amsterdam.
J Clin Oncol. 1995 Jul;13(7):1649-55. doi: 10.1200/JCO.1995.13.7.1649.
To compared the response rates and the toxicity of the new antifolate edatrexate (EDX) with that of methotrexate (MTX) in a randomized trial in patients with metastatic or recurrent squamous cell cancer of the head and neck (SCC) and to compare the durations of response and survival.
Two hundred seventy-three patients with SCC were randomized to receive either EDX or MTX as a weekly intravenous (IV) bolus injection. Doses of EDX were initially 80 mg/m2/wk, but because of the toxicity, this was later reduced to 70 mg/m2/wk. MTX was administered at a dose of 40 mg/m2/wk throughout. In both arms, two dose increments of 10% were scheduled in case of no toxicity.
Of 264 eligible patients, 131 were treated with EDX and 133 with MTX. There were five treatment-related deaths: four on EDX and one on MTX. Overall, toxicity was similar in both arms; however, stomatitis, skin toxicity, and hair loss were more pronounced on the EDX arm. The overall response rate was 21% (six complete responses [CRs] and 21 partial responses [PRs]) for EDX and 16% (nine CRs and 12 PRs) for MTX (P = .392). Responses were mainly seen in patients with locoregional disease. Tumors that originated from the hypopharynx responded poorly in comparison to tumors from other sites. The median duration of response was 6.1 months for EDX and 6.4 months for MTX (log-rank P = .262). There was no difference in overall or progression-free survival. The median survival duration was 6 months on both treatment groups.
Both EDX and MTX are moderately active against SCC. In this large phase III study, response rates, time to treatment failure, and overall survival appeared to be similar for both antifolates. However, EDX had more side effects than MTX and therefore cannot be recommended for routine palliative treatment of patients with SCC.
在一项针对转移性或复发性头颈部鳞状细胞癌（SCC）患者的随机试验中，比较新型抗叶酸药物依达曲沙（EDX）与甲氨蝶呤（MTX）的缓解率和毒性，并比较缓解持续时间和生存期。
273例SCC患者被随机分为两组，分别接受EDX或MTX每周一次的静脉推注。EDX的初始剂量为80mg/m²/周，但由于毒性反应，随后降至70mg/m²/周。MTX全程剂量为40mg/m²/周。若未出现毒性反应，两组均计划增加两个10%的剂量。
264例符合条件的患者中，131例接受EDX治疗，133例接受MTX治疗。有5例与治疗相关的死亡：EDX组4例，MTX组1例。总体而言，两组的毒性相似；然而，EDX组的口腔炎、皮肤毒性和脱发更为明显。EDX的总体缓解率为21%（6例完全缓解[CR]和21例部分缓解[PR]），MTX为16%（9例CR和12例PR）（P = 0.392）。缓解主要见于局部区域疾病患者。与其他部位的肿瘤相比，起源于下咽的肿瘤反应较差。EDX的中位缓解持续时间为6.1个月，MTX为6.4个月（对数秩检验P = 0.262）。总生存期或无进展生存期无差异。两个治疗组的中位生存期均为6个月。
EDX和MTX对SCC均有中等活性。在这项大型III期研究中，两种抗叶酸药物的缓解率、治疗失败时间和总生存期似乎相似。然而，EDX的副作用比MTX多，因此不推荐用于SCC患者的常规姑息治疗。
