Gemcitabine combined with oxaliplatin in pretreated patients with malignant pleural mesothelioma: an observational study

Abstract

BackgroundThe aim of this study was to investigate the efficacy and safety of oxaliplatin ± gemcitabine in patients with diffuse malignant pleural mesothelioma (MPM) pretreated with pemetrexed.MethodsThe study enrolled consecutive patients with relapsed MPM, all of them pretreated with a platin-pemetrexed-based chemotherapy. Oxaliplatin 80 mg/m2 was administered as monotherapy or in combination with gemcitabine 1000 mg/m2 given on day 1 and 8. Cycles were repeated every 21 days. The primary endpoints were response rate and disease control rate. Secondary endpoints included overall survival (OS), time to tumour progression (TTP), progression-free survival (PFS), time to treatment failure (TTF), and toxicity.ResultsBetween February 2005 and September 2007 29 patients (median age: 65.0 years, World Health Organisation (WHO) performance status: 0–3) were enrolled. The follow-up period encompassed 5.4 to 97.4 weeks (median: 24.3 weeks). Out of these 29 patients, 15 were treated in second, 10 in third, 3 in fourth and 1 in fifth line, respectively. The majority of the patients received the combination oxaliplatin and gemcitabine (n = 25 vs. 4; 86.2 vs. 13.8%).The median overall survival (OS) was 71.7 weeks (30.6–243.3 weeks), whereas survival from the start of oxaliplatin/gemcitabine-treatment was 24.3 weeks (5.4–97.3 weeks). Median time to tumour progression (TTP) was 9.3 weeks (3.0–67.6 weeks).Partial response (PR) was observed in 2 patients (6.9%), stable disease (SD) for at least three courses of treatment in 11 patients (37.9%). Thus, disease control rate was 44.8%, whereas 16 of 29 patients exhibited progressive disease (55.2%).The toxicity profile was favourable, with no WHO grade 4-toxicities, only few dose-reductions were performed due to non-symptomatic haematotoxicities (neutropenia, thrombopenia). Mild WHO grade 2 neurotoxicity was seen in 6 patients.ConclusionPemetrexed-pretreated patients with progressive MPM may benefit from a consecutive chemotherapy with oxaliplatin and gemcitabine without significant toxicity.

Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: A mono-institutional experience

“…The association of gemcitabine and oxaliplatin showed a disease control rate of 44.8%, with 2 (7%) partial responses and 11 (38%) disease stabilizations; overall survival and median time to tumor progression were 24.3 and 9.3 weeks respectively [22].…”

Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma

“… 29 Furthermore, for pemetrexed pretreated patients, the combination of dual-agents treatment with gemcitabine–vinorelbine or gemcitabine–oxaliplatin are reasonable palliative options. 30 , 31 Besides, re-treatment with pemetrexed is a feasible option in fit patients, especially in patients with longer PFS (>12 months) after first-line pemetrexed treatment. 32 The efficacy of second-line therapy remains unanswered at present and it is still an unmet need in this patient population.…”

Synergistic Antitumor Activity of Recombinant Human Apo2L/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in Combination with Carboplatin and Pemetrexed in Malignant Pleural Mesothelioma

“…Since 2003, when antifolate agents were introduced in the clinical management of this disease, the standard procedure chemotherapy is a platinum-based doublet plus pemetrexed or raltitrexed. [30][31][32][33] Recent studies tested biologic agents that target key oncogenic pathways, including phosphatidylinositol3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways, histone deacetylases, nuclear factor kB, and neoangiogenesis. 29 After the standard first-line pemetrexed/platinum combination, there is not a defined regimen for the secondline treatment of MPM, and the clinical benefits are uncertain.…”