-
Journal of Clinical Oncology : Official... May 2023
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Docetaxel; Lung Neoplasms; Antineoplastic Agents; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37196428
DOI: 10.1200/JCO.22.02871 -
Expert Opinion on Drug Metabolism &... Mar 2017Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human... (Review)
Review
Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities. Here, we summarize the pharmacogenomic information reported so far for genes involved in antifolate metabolism and transport and in MTX-related toxicity in HGOS patients. Expert opinion: Identification and validation of genetic biomarkers that significantly impact clinical antifolate treatment response and related toxicity may provide the basis for a future treatment modulation based on the pharmacogenetic and pharmacogenomic features of HGOS patients.
Topics: Antimetabolites, Antineoplastic; Bone Neoplasms; Folic Acid Antagonists; Humans; Methotrexate; Neoplasm Grading; Osteosarcoma; Pemetrexed; Pharmacogenetics; Trimetrexate
PubMed: 27758143
DOI: 10.1080/17425255.2017.1246532 -
ESMO Open Oct 2021Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed...
BACKGROUND
Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS).
PATIENTS AND METHODS
Patients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR).
RESULTS
From January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival.
CONCLUSIONS
Combination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.
Topics: Cisplatin; Humans; Ifosfamide; Pemetrexed; Sarcoma; Soft Tissue Neoplasms
PubMed: 34482181
DOI: 10.1016/j.esmoop.2021.100249 -
European Journal of Hospital Pharmacy :... Nov 2022To determine the physicochemical stability of pemetrexed diarginine in original vials, and after dilution in two commonly used infusion fluids (0.9% sodium chloride, 5%...
OBJECTIVES
To determine the physicochemical stability of pemetrexed diarginine in original vials, and after dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in polyolefin bags, stored under refrigeration (2-8°C) or at ambient temperature (22-25°C) exposed to light.
METHODS
Stability of pemetrexed diarginine injection concentrate was determined in the original glass vials with closed-system transfer device. Diluted pemetrexed diarginine infusion solutions were aseptically prepared by dilution of pemetrexed diarginine concentrate with either 0.9% sodium chloride or dextrose 5% in polyolefin bags, in amounts yielding pemetrexed diarginine concentrations of 4, 9 and 12 mg/mL. Test solutions were stored under refrigeration (2-8°C) or at ambient temperature (22-25°C) exposed to light. Pemetrexed diarginine concentrations were determined throughout a 14-day storage period using a stability-indicating HPLC assay. In addition, test solutions were visually examined for colour change and precipitation.
RESULTS
Pemetrexed diarginine injection concentrate with closed-system transfer device is shown to be physicochemically stable for up to 4 days when stored under refrigeration and for 1 day at room temperature. A browning of the pemetrexed diarginine concentrate solutions appeared 0n day 2 when stored at ambient temperature and on day 5 under refrigeration. Pemetrexed diarginine diluted in dextrose 5% and 0.9% sodium chloride was physicochemically stable for up to 4 days when stored under refrigeration and for 1 day at room temperature. A browning of the diluted solutions appeared on day 2 when stored at room temperature and on day 5 when stored under refrigeration.
CONCLUSIONS
Pemetrexed diarginine concentrate for solution stored under refrigeration with closed-system transfer device can be retained as a residual to reduce product losses. The analytical stability of pemetrexed diarginine in dextrose 5% and 0.9% sodium chloride under refrigeration enables our centralised unit to prepare this drug in advance.
Topics: Pemetrexed; Drug Storage; Drug Stability; Sodium Chloride; Drug Packaging; Pharmaceutical Solutions; Glucose
PubMed: 33658227
DOI: 10.1136/ejhpharm-2020-002620 -
World Journal of Surgical Oncology Jun 2022Prognosis in malignant peritoneal mesothelioma (MPM) remains poor, and the associated factors are unclear. Therefore, this study aimed to investigate the prognostic...
BACKGROUND
Prognosis in malignant peritoneal mesothelioma (MPM) remains poor, and the associated factors are unclear. Therefore, this study aimed to investigate the prognostic factors of MPM.
METHODS
A total of 52 female MPM patients treated in 2012-2017 were retrospectively analyzed. Kaplan-Meier survival curves were generated for survival analysis by the log-rank test. The Cox regression model was used for univariate and multivariate analyses.
RESULTS
Univariate analysis showed that median survival time (MST) was longer in the epithelioid type compared with the sarcomatoid type (12 months vs 5 months); cumulative survival rates at 12 months were 45.7% and 0%, respectively (P=0.005). MST was longer in patients with proliferating cell nuclear antigen (Ki67) ≤ 10% compared with those with Ki67 > 10% (15 months vs 11 months). Cumulative survival rates at 12 months were 60.0% and 28.1%, respectively (P=0.036). MSTs in patients administered peritoneal biopsy or adnexectomy + paclitaxel + platinum perfusion, peritoneal biopsy (or adnexectomy) + pemetrexed + platinum perfusion, cytoreductive surgery + paclitaxel + platinum perfusion, and cytoreductive surgery + pemetrexed + platinum perfusion were 6, 11, 12, and 24 months, respectively, with cumulative survival rates at 12 months of 0%, 35.7%, 45.5%, and 73.3%, respectively. Survival time after cytoreductive surgery combined with pemetrexed + platinum was the longest. In multivariate analysis, pathological type, T staging, and therapeutic regimen were independent prognostic factors of MPM (P < 0.05).
CONCLUSIONS
Prognosis in MPM is associated with pathological subtype, clinical staging, cytoreductive surgery, and subsequent pemetrexed use. Radical cytoreductive surgery and postoperative use of pemetrexed prolong survival.
Topics: Female; Humans; Ki-67 Antigen; Mesothelioma, Malignant; Paclitaxel; Pemetrexed; Peritoneal Neoplasms; Platinum; Prognosis; Retrospective Studies
PubMed: 35765009
DOI: 10.1186/s12957-022-02688-x -
Journal of Thoracic Oncology : Official... Sep 2021
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Pemetrexed
PubMed: 34242787
DOI: 10.1016/j.jtho.2021.06.021 -
Journal of Clinical Pharmacy and... Feb 2022Whether maintenance therapy with bevacizumab (Bev) + pemetrexed (Pem) can achieve greater clinical benefits than Bev or Pem alone for stage IIIB/IV nonsquamous non-small... (Meta-Analysis)
Meta-Analysis Review
The efficacy and toxicity of maintenance therapy with bevacizumab plus pemetrexed versus bevacizumab/pemetrexed alone for stage IIIB/IV nonsquamous non-small cell lung cancer: A meta-analysis of randomized controlled trials.
WHAT IS KNOWN AND OBJECTIVE
Whether maintenance therapy with bevacizumab (Bev) + pemetrexed (Pem) can achieve greater clinical benefits than Bev or Pem alone for stage IIIB/IV nonsquamous non-small cell lung cancer (NSCLC) remains unclear. We assessed the antitumour effect and toxicity of maintenance Bev+Pem versus maintenance with single-agent Bev/Pem in this meta-analysis.
METHODS
Appropriate randomized controlled trials (RCTs) were screened using electronic databases (Google Scholar, PubMed, Embase, Scopus, ScienceDirect, Ovid MEDLINE, Cochrane and Web of Science). The endpoints were progression-free survival (PFS), overall survival (OS) and adverse events (AEs).
RESULTS AND DISCUSSION
We included six RCTs that contained 2,447 patients receiving induction therapy with platinum-based combination therapies. The maintenance therapy Bev+Pem group had prolonged PFS (HR = 0.74, 95% CI 0.69-0.80, p < 0.00001) and OS (HR = 0.91, 95% CI 0.83-0.99, p = 0.02) compared with the Bev/Pem group. Moreover, we further analysed the PFS rate (PFSR) and OS rate (OSR) and found that the Bev+Pem group exhibited improved PFSR-0.5y, PFSR-1y, PFSR-1.5y, PFSR-2y and OS-2y, with preferable trends in OS-1y, OS-3y and OS-4y compared with the Bev/Pem single-agent maintenance therapy. In addition, subgroup analyses indicated that the Bev+Pem group had greater PFS and OS among patients aged <65 years, patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, and patients who never smoked. Regarding adverse events (AEs), the Bev+Pem group exhibited an increased occurrence of anaemia, fatigue, thrombocytopenia and anorexia.
WHAT IS NEW AND CONCLUSION
For stage IIIB/IV nonsquamous NSCLC patients, maintenance therapy with Bev+Pem offers an increased survival outcome (PFS, OS) compared with monotherapy. However, the increased incidence of AEs should not be neglected.
Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Pemetrexed; Progression-Free Survival; Randomized Controlled Trials as Topic; Sex Factors
PubMed: 34617297
DOI: 10.1111/jcpt.13534 -
Frontiers of Medicine Aug 2022Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the...
Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Pemetrexed; Platinum; Retrospective Studies; Treatment Outcome
PubMed: 35290596
DOI: 10.1007/s11684-021-0827-8 -
Yakugaku Zasshi : Journal of the... 2023Chemotherapy-induced myositis is a severe adverse event caused by chemotherapeutic agents such as immune checkpoint inhibitors (ICIs) or cytotoxic agents. We experienced...
Chemotherapy-induced myositis is a severe adverse event caused by chemotherapeutic agents such as immune checkpoint inhibitors (ICIs) or cytotoxic agents. We experienced a patient with gefitinib-induced myositis with symptoms of muscle cramps and stiffness in the limbs, and reported the treatment process. A 70-year-old woman received four courses of carboplatin (CBDCA)+pemetrexed (PEM)+gefitinib (intravenous CBDCA area under the curve (AUC) 5 and PEM 500 mg/m, every 3 weeks, and oral gefitinib 250 mg daily), for epidermal growth factor receptor (EGFR) mutation-positive stage IV lung cancer treatment; followed by seven courses of PEM+gefitinib, and continued gefitinib monotherapy thereafter. Myositis occurred 5 months after the initiation of gefitinib monotherapy. She developed strong limb cramps despite regular oral administration of 400 mg acetaminophen three times a day and complained of pain on a numeric rating scale of 10/10. Her creatine kinase (CK) was elevated from the second course of CBDCA+PEM+gefitinib but was stable at grade 1-2 thereafter. However, the muscle symptoms disappeared with CK normalization within a few days of gefitinib discontinuation due to disease progression. The Naranjo Adverse Drug Reaction Scale score was 6, suggesting a probable association. Osimertinib (an EGFR tyrosine kinase inhibitor)-induced myositis has been reported, but similar events were first observed with gefitinib in this case. Consequently, when treating with gefitinib, myositis, including the CK variation, should be monitored and appropriately managed with multidirectional treatment.
Topics: Humans; Female; Aged; Myositis; Gefitinib; Muscle Cramp; Lung Neoplasms; Carboplatin; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 37394456
DOI: 10.1248/yakushi.23-00007 -
Frontiers in Immunology 2023Pleural mesothelioma (PM) is an aggressive and rare disease, characterized by a very poor prognosis. For almost two decades, the world standard treatment regimen for... (Review)
Review
Pleural mesothelioma (PM) is an aggressive and rare disease, characterized by a very poor prognosis. For almost two decades, the world standard treatment regimen for unresectable PM has consisted of a platinum-based drug plus pemetrexed, leading to an overall survival of approximately 12 months. The dramatic therapeutic scenario of PM has recently changed with the entry into the clinic of immune checkpoint inhibition, which has proven to be an effective approach to improve the survival of PM patients. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced PM.
Topics: Humans; Mesothelioma; Mesothelioma, Malignant; Immunotherapy; Pleural Neoplasms; Pemetrexed
PubMed: 38259475
DOI: 10.3389/fimmu.2023.1333661