Jänne Pasi A, Simon George R, Langer Corey J, Taub Robert N, Dowlati Afshin, Fidias Panos, Monberg Matthew, Obasaju Coleman, Kindler Hedy
Dana Farber Cancer Institute, Lowe Center for Thoracic Oncology, 44 Binney St, Dana D820A, Boston, MA 02115, USA.
J Clin Oncol. 2008 Mar 20;26(9):1465-71. doi: 10.1200/JCO.2007.14.7611.
Pemetrexed and gemcitabine have single-agent activity in malignant pleural mesothelioma (MPM). The combination of pemetrexed/gemcitabine has not previously been studied in MPM to our knowledge.
Patients with histologic or cytologic diagnosis of MPM were included. Cohort 1 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 8, and cohort 2 received gemcitabine 1,250 mg/m(2) on days 1 and 8, with pemetrexed 500 mg/m(2) on day 1. Cycles were repeated every 21 days; all patients were supplemented with folic acid and vitamin B(12) and received dexamethasone.
One hundred eight patients (cohort 1, n = 56; cohort 2, n = 52) with pleural mesothelioma were enrolled. Among assessable patients, response rate was 26.0% in cohort 1 and 17.1% in cohort 2. Median time to disease progression was 4.34 months for cohort 1 and 7.43 months for cohort 2. Median survival was 8.08 months for cohort 1 (1-year survival = 31.14%) and 10.12 months for cohort 2 (1-year survival = 45.80%). In cohorts 1 and 2, incidence of grade 4 neutropenia was 25.0% and 29.4%, grade 4 thrombocytopenia was 14.3% and 3.9%, grade 3 or 4 anemia was 5.4% and 5.9%, and grade 3 or 4 fatigue was 23.2% and 15.7%, respectively.
The combination of pemetrexed and gemcitabine resulted in moderate clinical activity in MPM. However, the median survival times are similar to those with single-agent pemetrexed and inferior to outcomes observed with cisplatin in combination with an antifolate.
培美曲塞和吉西他滨在恶性胸膜间皮瘤（MPM）中具有单药活性。据我们所知，培美曲塞/吉西他滨联合用药此前尚未在MPM中进行过研究。
纳入经组织学或细胞学诊断为MPM的患者。第1组在第1天和第8天接受吉西他滨1250mg/m²，在第8天接受培美曲塞500mg/m²；第2组在第1天和第8天接受吉西他滨1250mg/m²，在第1天接受培美曲塞500mg/m²。每21天重复一个周期；所有患者均补充叶酸和维生素B12，并接受地塞米松治疗。
108例胸膜间皮瘤患者（第1组n = 56；第2组n = 52）入组。在可评估的患者中，第1组的缓解率为26.0%，第2组为17.1%。第1组疾病进展的中位时间为4.34个月，第2组为7.43个月。第1组的中位生存期为8.08个月（1年生存率 = 31.14%），第2组为10.12个月（1年生存率 = 45.80%）。在第1组和第2组中，4级中性粒细胞减少的发生率分别为25.0%和29.4%，4级血小板减少的发生率分别为14.3%和3.9%，3级或4级贫血的发生率分别为5.4%和5.9%，3级或4级疲劳的发生率分别为23.2%和15.7%。
培美曲塞和吉西他滨联合用药在MPM中产生了适度的临床活性。然而，中位生存时间与培美曲塞单药治疗相似，且低于顺铂联合抗叶酸药物的治疗效果。
