Simon George R, Verschraegen Claire F, Jänne Pasi A, Langer Corey J, Dowlati Afshin, Gadgeel Shirish M, Kelly Karen, Kalemkerian Gregory P, Traynor Anne M, Peng Guangbin, Gill John, Obasaju Coleman K, Kindler Hedy L
Thoracic Oncology Program and Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, MRC-4W, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.
J Clin Oncol. 2008 Jul 20;26(21):3567-72. doi: 10.1200/JCO.2007.15.2868.
Pemetrexed in combination with cisplatin is approved for the treatment of pleural mesothelioma and is active in malignant peritoneal mesothelioma (MPeM). Pemetrexed and gemcitabine are synergistic in preclinical models, but the activity of this combination in MPeM is unknown. This clinical study assessed safety and efficacy of pemetrexed plus gemcitabine in chemotherapy-naïve patients with MPeM.
Treatment consisted of gemcitabine 1,250 mg/m(2) on days 1 and 8, and pemetrexed 500 mg/m(2) on day 8, administered immediately before gemcitabine. Treatment was repeated every 21 days for six cycles or until disease progression. All patients received folic acid, vitamin B(12), and dexamethasone supplementation. End points included tumor response, toxicity, time to disease progression (TTPD), and overall survival (OS). Disease control rate (DCR) was also calculated.
Twenty patients were enrolled between December 2002 and May 2004. The confirmed response rate was 15% (95% CI, 3.2% to 37.9%), with three patients experiencing a partial response. The DCR was 50% (95% CI, 27.2% to 72.8%). The most common grade 3 to 4 nonhematologic toxicities included fatigue (20%), constipation (10%), vomiting (10%), and dehydration (10%). Hematologic toxicities included grade 3 to 4 neutropenia (60%) and febrile neutropenia (10%). One patient death was attributed to treatment. Median TTPD and OS times were 10.4 months and 26.8 months, respectively.
The combination of pemetrexed plus gemcitabine was active in patients with MPeM with a notably high incidence of neutropenia. Median TTPD and OS seem promising. This regimen may provide an alternative to standard therapies, especially for patients who cannot tolerate a platinum-based regimen.
培美曲塞联合顺铂已被批准用于治疗胸膜间皮瘤，且对恶性腹膜间皮瘤（MPeM）有效。培美曲塞和吉西他滨在临床前模型中具有协同作用，但该联合方案在MPeM中的活性尚不清楚。本临床研究评估了培美曲塞加吉西他滨在未经化疗的MPeM患者中的安全性和疗效。
治疗方案为第1天和第8天给予吉西他滨1250mg/m²，第8天给予培美曲塞500mg/m²，在吉西他滨给药前立即给予。每21天重复治疗6个周期或直至疾病进展。所有患者均接受叶酸、维生素B12和地塞米松补充治疗。终点指标包括肿瘤反应、毒性、疾病进展时间（TTPD）和总生存期（OS）。还计算了疾病控制率（DCR）。
2002年12月至2004年5月期间共纳入20例患者。确认的缓解率为15%（95%CI，3.2%至37.9%），3例患者出现部分缓解。DCR为50%（95%CI，27.2%至72.8%）。最常见的3至4级非血液学毒性包括疲劳（20%）、便秘（10%）、呕吐（10%）和脱水（10%）。血液学毒性包括3至4级中性粒细胞减少（60%）和发热性中性粒细胞减少（10%）。1例患者死亡归因于治疗。中位TTPD和OS时间分别为10.4个月和26.8个月。
培美曲塞加吉西他滨联合方案对MPeM患者有效，中性粒细胞减少发生率显著较高。中位TTPD和OS似乎很有前景。该方案可能为标准治疗提供替代方案，尤其是对于不能耐受铂类方案的患者。
