Efficacy and safety of pemetrexed on recurrent primary central nervous system lymphomas in China: a prospective study

Abstract

BackgroundPemetrexed, a new and novel agent for primary central nervous system lymphomas (PCNSLs), has shown to be efficient as a savage therapy for recurrent PCNSLs. However, more studies are needed. A prospective study was performed on 17 recurrent PCNSL patients with pemetrexed at Shandong Tumor Hospital in China to assess the efficacy and safety of pemetrexed for recurrent PCNSL patients.Materials and methodsThe medical records and imaging data on all the cases of recurrent PCNSL patients with pemetrexed in our study were collected during August 2012 and April 2015. Folic acid, B12, and dexamethasone were used to induce toxicities related to pemetrexed. Patients were treated with pemetrexed at a dose of 900 mg/m2 intravenously every 3 weeks, and one cycle consists of 6 weeks.ResultsA total of 17 cases of recurrent PCNSL patients were enrolled in our study, including 10 males and 7 females with a median age of 66.2 years (ranging from 35 to 81). After the treatment, five cases had complete remission, with partial remission in five cases, stable disease in four cases, and progressive disease in three cases. Consequently, the overall response rate was 58.8%, and the disease control rate was 82.4%. The median overall survival was 7.8 months (95% confidence interval: 5.9–9.6 months) in the study of recurrent PCNSL patients.ConclusionThis study has been the first clinical trial that applied pemetrexed to treat recurrent PCNSL patients in China, and results indicated that chemotherapy using large pemetrexed may become an effective treatment for PCNSL recurrence with modest toxicity.

Pemetrexed exerts anticancer effects by inducing G0/G1‑phase cell cycle arrest and activating the NOXA/Mcl‑1 axis in human esophageal squamous cell carcinoma cells

“…It is able to inhibit the synthesis of purine and pyrimidine by blocking dihydrofolate reductase, thymidylate synthase and glycinamide ribonucleotide formyltransferase (25). Recently, pemetrexed has been reported to exhibit antitumor effects in various solid tumors (19,25). The present study aimed to determine whether pemetrexed was able to exert anticancer effects in ESCC and to elucidate the underlying molecular mechanism.…”

“…Pemetrexed is a clinically available multi-target antifolate cytotoxic agent (19). It is able to inhibit the synthesis of purine and pyrimidine by blocking dihydrofolate reductase, thymidylate synthase and glycinamide ribonucleotide formyltransferase (25). Recently, pemetrexed has been reported to exhibit antitumor effects in various solid tumors (19,25).…”

<p>Systemic Approach to Recurrent Primary CNS Lymphoma: Perspective on Current and Emerging Treatment Strategies</p>

“…Survival data and toxicity profile were comparable as well. 35 A retrospective study of pemetrexed as salvage for not only relapsed PCNSL (n=17 evaluable PCNSL) but also secondary CNSL (SCNSL; n=12) illustrated an OR rate of 64.7% (all CR) and 59.3% (with 2 CR), respectively, further illustrating efficacy of this drug in the setting of relapsed CNS lymphoma. 36 Treatment of pemetrexed has also been studied in combination with rituximab in a prospective trial with 27 patients, showed an ORR of 62.9% with 22% of patients reaching a CR.…”

Primary central nervous system lymphoma

“…Pemetrexed, a folate antimetabolite with a broader spectrum of activity than MTX demonstrated activity in a case series of 17 patients with recurrent PCNSL and an overall radiographic response rate of 58.8% and a median OS of 7.8 months; three patients died of infection. 76 As with MTX, the main side effects include myelosuppression, gastrointestinal reactions and infections; doses up to 900 mg/m 2 are relatively well tolerated. 77 In elderly patients, pemetrexed (600 mg/m 2 ) as induction therapy appears to be feasible and well tolerated, with a median OS of 19.5 months in a case series.…”