Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): a phase II trial.

The synergistic activity of pemetrexed with platinum agents in non-small cell lung cancer (NSCLC) and the renal safety of carboplatin suggest a balanced benefit/risk profile for this combination in elderly patients. This multicenter, single-arm, phase II study included 62 patients (≥70 years) with chemonaïve advanced NSCLC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and assigned to receive 6 cycles of 3-weekly pemetrexed 500 mg/m(2) and carboplatin AUC 5. The primary endpoint was objective tumor response rate (ORR). Sixty-two patients received at least one dose of chemotherapy. Median age was 76.4 years [70.2-86] and all patients had PS 0 (16.1%) or PS 1 (83.9%). Stage IIIb disease in 21% patients and stage IV in 79% patients. Non-squamous cell carcinoma in 66.1% patients (adenocarcinoma 51.6%, large cell carcinoma 8.1%, other 6.5%) and squamous cell carcinoma in 33.9% patients. ORR was 28.6% (95% confidence interval [CI], 16.58-43.26), all were partial responses. Stable disease rate was 42.9%. Grade 3/4 toxicities related to study drugs were: asthenia 16.1%, anorexia 4.8%, diarrhea 3.2%, neutropenia 51.6%, leucopenia 30.7%, thrombocytopenia 29%, anemia 19.4%. One related fatal septic shock occurred. In advanced NSCLC, pemetrexed use is restricted to non-squamous histology. The combination pemetrexed-carboplatin could be a valuable treatment option in elderly patients. Neutropenia was the most common toxicity. The ORR is within the range of data reported for pemetrexed-carboplatin in the general NSCLC population (24-31%).

Gervais R ，Robinet G ，Clément-Duchêne C ，Denis F ，El Kouri C ，Martin P ，Chouaki N ，Bourayou N ，Morère JF ... -  《-》

Phase II study of carboplatin and pemetrexed in advanced non-squamous, non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0902.

Kim YH ，Hirabayashi M ，Togashi Y ，Hirano K ，Tomii K ，Masago K ，Kaneda T ，Yoshimatsu H ，Otsuka K ，Mio T ，Tomioka H ，Suzuki Y ，Mishima M ... -  《-》

Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2.

Zukin M ，Barrios CH ，Pereira JR ，Ribeiro Rde A ，Beato CA ，do Nascimento YN ，Murad A ，Franke FA ，Precivale M ，Araujo LH ，Baldotto CS ，Vieira FM ，Small IA ，Ferreira CG ，Lilenbaum RC ... -  《-》

A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer.

Pemetrexed plus cisplatin was approved for first-line treatment of non-small-cell lung cancer (NSCLC) in patients with nonsquamous histology after initiation of this study. This phase II study evaluated pemetrexed plus cisplatin and pemetrexed plus carboplatin as first-line treatments for stage IIIB/IV NSCLC. The patients were randomized (1:1) to 2 parallel arms: pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) or pemetrexed (500 mg/m(2)) plus carboplatin (area under the curve 6) day 1 every 3 weeks (maximum, 6 cycles). Progression-free survival (PFS) was the primary objective; secondary objectives included overall survival (OS), 1-year survival, and safety. Sixty-five patients were randomized to each treatment arm. The patients treated with pemetrexed plus cisplatin had a median age of 64 years and were predominantly men (42 [64.6%]) with nonsquamous histology (53 [81.5%]), stage IV (61 [92.4%]) disease, and a performance status of 0 (40 [61.5%]). Median PFS was 6.0 months, 6-month PFS rate was 50.5%, median OS was 11.7 months, and 1-year survival rate was 47.5%. Drug-related grade 3/4 toxicities included neutropenia (11 [16.9%]), anemia (5 [7.7%]), thrombocytopenia (2 [3.1%]), and nausea (3 [4.6%]). Patients treated with pemetrexed plus carboplatin had a median age of 63 years, were predominantly men (46 [70.8%]) with nonsquamous histology (52 [80.0%]), stage IV (58 [86.6%]) disease, and a performance status of 0 (45 [69.2%]). The median PFS was 4.7 months, the 6-month PFS rate was 34.9%, median OS was 8.9 months, and 1-year survival rate was 39.2%. Drug-related grade 3/4 toxicities included neutropenia (17 [26.2%]), thrombocytopenia (11 [16.9%]), anemia (7 [10.8%]), and nausea (5 [7.7%]). Both the pemetrexed plus cisplatin and pemetrexed plus carboplatin arms met their primary endpoints and demonstrated efficacy and tolerability as first-line therapy in patients with advanced NSCLC. http://ClinicalTrials.gov: NCT00402051.

Schuette WH ，Gröschel A ，Sebastian M ，Andreas S ，Müller T ，Schneller F ，Guetz S ，Eschbach C ，Bohnet S ，Leschinger MI ，Reck M ... -  《-》

Phase II study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer.

Patel JD ，Hensing TA ，Rademaker A ，Hart EM ，Blum MG ，Milton DT ，Bonomi PD ... -  《-》