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Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective study of induction therapy for primary central nervous system lymphoma in Chinese.

ABSTRACT: We performed a retrospective study of 49 patients with newly diagnosed primary central nervous system lymphoma (PCNSL), to compare the efficacy and safety of different high-dose methotrexate (HD-MTX) based systemic chemotherapy regimens as induction therapy. 25 patients received AB?±?R alternative regimen (consist methotrexate, ifosfamide, vindesine, dexamethasone, carmustine and teniposide), while others received HD-MTX?±?R regimen. The complete response rate and overall response rate of AB?±?R group and HD-MTX?±?R group were 36.83% vs. 33.33%, and 68.42% vs. 71.43%, while the 2-year OS and PFS rate were 71.43% vs. 74.62%, and 42.86% vs. 54.64%, respectively. In Age?>?60 subgroup, the 2-year OS and PFS rate of AB?±?R group and HD-MTX?±?R group were 81.82% vs. 33.33%, and 54.55% vs. 33.33%. No significant differences were found in grade 3 or 4 toxicity rate. Generally, HD-MTX?±?R regimen was not inferior to AB?±?R alternative regimen, but AB?±?R alternative regimen seemed achieving more survival benefits in the elderly. We suggest to adjust HD-MTX?±?R regimen by changing the dose-reduction strategy especially in elderly patients and adding other powerful drugs that can well penetrate blood-brain barrier to improve the efficacy.

SUBMITTER: Han X

PROVIDER: S-EPMC5719046 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective study of induction therapy for primary central nervous system lymphoma in Chinese.

Han Xiao X Ji Yali Y Ouyang Mingqi M Zhu Tienan T Zhou Daobin D

Scientific reports 20171206 1

We performed a retrospective study of 49 patients with newly diagnosed primary central nervous system lymphoma (PCNSL), to compare the efficacy and safety of different high-dose methotrexate (HD-MTX) based systemic chemotherapy regimens as induction therapy. 25 patients received AB ± R alternative regimen (consist methotrexate, ifosfamide, vindesine, dexamethasone, carmustine and teniposide), while others received HD-MTX ± R regimen. The complete response rate and overall response rate of AB ± R ...[more]

PMID: 29213063

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Project description:Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment.

Project description:Background:Primary central nervous system lymphomas (PCNSL) are extranodal malignant non-Hodgkin lymphomas (NHL) that arise exclusively in central nervous system (CNS). Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype. Purpose:To evaluate whether nano drug-loading system-mediated magnetic-targeted thermochemotherapy could produce a better therapeutic effect than single chemotherapy while reducing the use of chemotherapeutic drugs. Methods:Six groups (control, Fe3O4, MTX, Fe3O4@MTX, Fe3O4 with hyperthermia and Fe3O4@MTX with hyperthermia) were set. Tumor cell apoptosis in each treatment group was detected by flow cytometry. Apoptosis-related gene expressions Caspase-3, Bax and Bcl-2 were detected by qPCR and Western blot; intracranial tumor model of PCNSL was established by intracranial injection of OCI-LY18 tumor cells into BALB/c-Nude mice. Magnetic resonance imaging (MRI) was used to monitor tumor progression and H&E staining was used to observe pathological changes of the tumor tissue. Results:In vitro, compared with chemotherapy alone, apoptosis rate of Fe3O4@MTX mediated thermochemotherapy group was significantly increased, and expression of apoptosis-inducing gene Caspase-3 and Bax were significantly upregulated in OCI-LY18 cells, while expression of apoptosis-inhibiting Bcl-2 gene was significantly downregulated. In vivo, MRI showed successful generation of intracranial tumor, and tumor volume was significantly smaller in combined thermochemotherapy group than in single chemotherapy group. H&E staining result of tumor tissues in each group was consistent with MRI; tumor cells were significantly reduced in thermochemotherapy group. Expression of apoptosis-related gene Caspase-3 and Bax were significantly upregulated in tumor tissues, while expression of Bcl-2 gene was significantly downregulated. Conclusion:These results demonstrated in vivo and in vitro that the combined thermochemotherapy of Fe3O4@MTX MNPs was superior to the single MTX chemotherapy with less dosage, which may promote apoptosis of DLBCL cells through the mitochondrial apoptotic pathway and provided a new way for the treatment of PCNSL.

Dataset Information

Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective study of induction therapy for primary central nervous system lymphoma in Chinese.

Publications

Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective study of induction therapy for primary central nervous system lymphoma in Chinese.

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