Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
Cancer. 2012 Oct 1;118(19):4694-705. doi: 10.1002/cncr.27449. Epub 2012 Mar 20.
Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN.
In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m(2) ) plus cisplatin (75 mg/m(2) ; n = 398) or placebo plus cisplatin (75 mg/m(2) ; n = 397) to assess overall survival (OS) and secondary endpoints.
Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P = .082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors.
Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers.
复发性或转移性头颈部鳞状细胞癌（SCCHN）的生存率较差。铂类化疗通常是一线治疗。培美曲塞在 SCCHN 中具有单药活性，并与顺铂联合用于其他肿瘤。本试验研究了培美曲塞联合顺铂治疗 SCCHN 的疗效。
在一项双盲 3 期试验中，既往未接受转移性疾病系统治疗的复发性或转移性 SCCHN 患者被随机分配至培美曲塞（500mg/m2）+顺铂（75mg/m2；n=398）或安慰剂+顺铂（75mg/m2；n=397）组，以评估总生存期（OS）和次要终点。
培美曲塞联合顺铂组的中位 OS 为 7.3 个月，安慰剂联合顺铂组为 6.3 个月（风险比[HR]，0.87；95%置信区间[CI]，0.75-1.02；P=0.082）。两组的中位无进展生存期（PFS，月）相似（培美曲塞联合顺铂组，3.6；安慰剂联合顺铂组，2.8；HR，0.88；95%CI，0.76-1.03；P=0.166）。在体能状态 0 或 1 的患者中，培美曲塞联合顺铂（n=347）组的 OS 和 PFS 长于安慰剂联合顺铂（n=343）组（8.4 与 6.7 个月；HR，0.83；P=0.026；4.0 与 3.0 个月；HR，0.84；P=0.044）。在口咽癌患者中，培美曲塞联合顺铂（n=86）组的 OS 和 PFS 长于安慰剂联合顺铂（n=106）组（9.9 与 6.1 个月；HR，0.59；P=0.002；4.0 与 3.4 个月；HR，0.73；P=0.047）。培美曲塞联合顺铂的毒性与其他肿瘤的研究一致。
与安慰剂联合顺铂相比，培美曲塞联合顺铂并未显著改善意向治疗人群的生存。然而，在预先指定的亚组分析中，培美曲塞联合顺铂在体能状态 0 或 1 或口咽癌患者中显示出 OS 和 PFS 优势。
