Tomudex (raltitrexed) / Pfizer, AstraZeneca 
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  • ||||||||||  Preclinical, Journal:  Anticancer Drugs for Intra-Arterial Treatment of Colorectal Cancer Liver Metastases: In-Vitro Screening after Short Exposure Time. (Pubmed Central) -  Aug 7, 2021   
    The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations...Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
  • ||||||||||  methotrexate / Generic mfg.
    Journal:  Initial Stages of Spontaneous Binding of Folate-Based Vectors to Folate Receptor-α Observed by Unbiased Molecular Dynamics. (Pubmed Central) -  Aug 6, 2021   
    Only folate, 5-methyltetrahydrofolate, and raltitrexed bind selectively at the active site of the receptor...Pemetrexed adsorbs nonspecifically on the protein surface, while methotrexate and pteroyl ornithine couple much less to the receptor...Analysis of the interactions between the ligands and FRα shows that in order to accomplish specific binding to the active site, a combination of hydrogen bonding, π-stacking, and van der Waals and Coulomb attraction should be feasible simultaneously for the vector molecule. The reported results demonstrate that it is possible to observe receptor-ligand binding without applying bias by representing the local environment as close as possible and contain important molecular-level guidelines for the design of folate-based systems for targeted delivery of anticancer drugs.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Exposure-Response Analysis of Raltitrexed Assessing Liver Toxicity. (Pubmed Central) -  Jul 28, 2021   
    Completing this trial as planned would provide further valuable insights. These results advocate for the use of creatinine clearance and sex to determine the RTX dose instead of BSA.
  • ||||||||||  methotrexate / Generic mfg.
    Preclinical, Journal:  Mechanical stress induced protein precipitation method for drug target screening. (Pubmed Central) -  Jun 8, 2021   
    Besides, DHFR was demonstrated to be a target of Raltitrexed, which has not been revealed by any other modification-free drug target discovery method yet. Thus, MSIPP is a complementary method to other drug target screening methods.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  A pure molecular drug hydrogel for post-surgical cancer treatment. (Pubmed Central) -  May 15, 2021   
    Delivered as a hydrogel, raltitrexed could effectively decrease tumor recurrence rate and promote the inhibition of tumor growth in vivo. This raltitrexed self-delivery hydrogel has the potential to serve as a powerful auxiliary implement for preventing postoperative local tumor recurrence.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Structural Bases for the Synergistic Inhibition of Human Thymidylate Synthase and Ovarian Cancer Cell Growth by Drug Combinations. (Pubmed Central) -  May 1, 2021   
    To show that crystallographic and inhibition kinetic information can provide indicators of cancer cell growth inhibition by combinations of two anti-human thymidylate synthase (hTS) drugs, we obtained the X-ray crystal structure of the hTS:raltitrexed:5-fluorodeoxyuridine monophosphate (FdUMP) complex...When administered in combination to A2780 and A2780/CP ovarian cancer cells, the two drugs inhibited ovarian cancer cell growth additively/synergistically. Together, these results support the idea that X-ray crystallography can provide structural indicators for designing combinations of hTS (or any other target)-directed drugs to accelerate preclinical research for therapeutic application.
  • ||||||||||  AiTan (rivoceranib) / HLB Bio Group, Avastin (bevacizumab) / Roche, AiRuiKa (camrelizumab) / Incyte
    [VIRTUAL] Camrelizumab plus apatinib combined with TACE and cryoablation in the first-line treatment of advanced hepatocellular carcinoma. () -  Apr 28, 2021 - Abstract #ASCO2021ASCO_1572;    
    The IMbrave 50 trial has reported the successful efficacy of atezolizumab and bevacizumab combination therapy in advanced hepatocellular carcinoma, which indicate the potential efficacy of combination of immunotherapy and antiangiogenesis therapy in HCC patients...TACE was administrated at the first treatment cycles on day 1or 2, the chemotherapy regimens included 100-150mg oxaliplatin, 750-1000mg fluorouracil, or 30-50 mg lobaplatin, raltitrexed 2-4mg, and epirubicin 40-80 mg...TACE and cryoablation was given as combination therapy and the periods were assessed by the investigator . The primary endpoint is objective response rate (complete or partial response according to mRECIST) and Progression-Free-Survival (Time ranges from random to the first occurrence of disease progression or death from any cause).
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Enrollment closed, Trial completion date, Trial primary completion date:  Raltitrexed Concurrent With Radiotherapy for Elderly Chinese Patients With Squamous Cell Carcinoma of Esophagus (clinicaltrials.gov) -  Apr 6, 2021   
    P2,  N=32, Active, not recruiting, 
    The primary endpoint is objective response rate (complete or partial response according to mRECIST) and Progression-Free-Survival (Time ranges from random to the first occurrence of disease progression or death from any cause). Recruiting --> Active, not recruiting | Trial completion date: Jul 2022 --> Mar 2022 | Trial primary completion date: Jul 2019 --> Jan 2022
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Tolerability of pemetrexed and oxaliplatin in the treatment of stage III colon cancer during raltitrexed shortage. (Pubmed Central) -  Mar 30, 2021   
    However, the patient also experienced progressive neuropathy which required a dose reduction and subsequent discontinuation of oxaliplatin. Overall, pemetrexed and oxaliplatin's tolerability seems comparable to other regimens used to treat colorectal cancer and could potentially be an option to consider in the future for alternative treatment of colorectal cancer pending further trials.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    New P1 trial:  Raltitrexed in HIPEC (clinicaltrials.gov) -  Feb 18, 2021   
    P1,  N=15, Recruiting, 
  • ||||||||||  Avastin (bevacizumab) / Roche
    Trial completion, Enrollment change:  Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer (clinicaltrials.gov) -  Feb 3, 2021   
    P2,  N=62, Completed, 
    Our study suggests that raltitrexed combined with cisplatin is a safe and effective concurrent chemotherapy regimen and it might be used as an alternative for cisplatin/5-FU and cisplatin/docetaxel in CCRT for EC patients. Active, not recruiting --> Completed | N=46 --> 62
  • ||||||||||  AiTan (rivoceranib) / HLB Bio Group, Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Raltitrexed Enhances the Antitumor Effect of Apatinib in Human Esophageal Squamous Carcinoma Cells via Akt and Erk Pathways. (Pubmed Central) -  Dec 10, 2020   
    Western blot analysis showed that phosphorylation levels of Erk, Akt, and invasiveness-associated protein matrix metalloproteinases-9 (MMP-9) were decreased in the combination group. Taken together, these results indicate that raltitrexed enhances the antitumor effects of apatinib on human ESCC cells by down-regulating phosphorylation of Akt and Erk, implying a combination of raltitrexed and apatinib might be an effective option for treating esophageal squamous cell carcinoma patients.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Acceleration of interstitial lung disease induced by raltitrexed. (Pubmed Central) -  Oct 28, 2020   
    HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate and advanced stage HCC, and further evaluation is warranted. The clinical pattern of rapid progression with steroid response highlights the potential for significant acceleration of interstitial lung disease by raltitrexed.
  • ||||||||||  Avastin (bevacizumab) / Roche, Tomudex (raltirexed) / Pfizer, AstraZeneca, irinotecan / Generic mfg.
    [VIRTUAL] First-line chemotherapy with raltitrexed in metastatic colorectal cancer: An AGEO multicentre study (On-Demand) -  Jul 21, 2020 - Abstract #ESMO2020ESMO_738;    
    Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapy...The different regimens were: raltitrexed (n=8), TOMOX (n=40), TOMIRI (n=8), raltitrexed bevacizumab (n=1), TOMOX bevacizumab (n=12), TOMIRI bevacizumab (n=4) and TOMOX panitumumab (n=1)...Legal entity responsible for the study: AGEO. Funding: Has not received any funding.
  • ||||||||||  fluorouracil / Generic mfg., Tomudex (raltirexed) / Pfizer, AstraZeneca, irinotecan / Generic mfg.
    P2 data, Journal:  S-1 plus Raltitrexed for Refractory Metastatic Colorectal Cancer: A Phase II Trial. (Pubmed Central) -  May 13, 2020   
    Trial completion date: Sep 2018 --> Sep 2019 | Recruiting --> Terminated; difficultly recruiting S-1 combined with raltitrexed for refractory mCRC showed moderate effect, and it is worthy of further study as third- or later-line therapy in mCRC.
  • ||||||||||  Tomudex (raltirexed) / Pfizer, AstraZeneca
    Biomarker, Journal:  MYC predetermines the sensitivity of gastrointestinal cancer to antifolate drugs through regulating TYMS transcription. (Pubmed Central) -  Mar 22, 2020   
    HAI plus chemo-filtration followed by target therapy, with drug regimens selected by liquid biopsy precision oncotherapy, is a safe and efficacious alternative therapeutic strategy for unresectable CRCLM in progression after two lines of systemic therapy and should be considered for a multicentre prospective phase III study, to fully confirm this potential. Our study unveils a mechanism of how TYMS is transcriptionally regulated by MYC, and provides rationales for the precise use of TYMS inhibitors in the clinic.
  • ||||||||||  Tomudex (raltirexed) / Pfizer, AstraZeneca
    Journal:  Formulation of Folate-Modified Raltitrexed-Loaded Nanoparticles for Colorectal Cancer Theranostics. (Pubmed Central) -  Feb 10, 2020   
    Imaging of the CRC tumors alone showed a higher average fluorescence from NPs accumulated in animals treated with the coated NPs, with the majority of RTX NP-treated animals showing the consistently-highest mean tumoral accumulation. Overall, these results contribute to the development of LbL formulations in CRC theranostic applications.
  • ||||||||||  Tomudex (raltirexed) / Pfizer, AstraZeneca, Jie Bai Shu (nedaplatin) / Simcere
    Retrospective data, Journal:  Concurrent chemoradiotherapy with raltitrexed and nedaplatin regimen for esophageal squamous cell carcinoma. (Pubmed Central) -  Feb 1, 2020   
    Overall, these results contribute to the development of LbL formulations in CRC theranostic applications. Concurrent chemoradiotherapy with raltitrexed and nedaplatin agents frequently caused myelosuppression but was highly active and suggested to be a promising treatment option for locally advanced ESCC.
  • ||||||||||  Tomudex (raltirexed) / Pfizer, AstraZeneca
    PK/PD data, Journal:  Hepatic Artery and Peripheral Vein Pharmacokinetics of Raltitrexed in Swine After the Administration of a Hepatic Arterial Infusion. (Pubmed Central) -  Jan 25, 2020   
    Concurrent chemoradiotherapy with raltitrexed and nedaplatin agents frequently caused myelosuppression but was highly active and suggested to be a promising treatment option for locally advanced ESCC. The pharmacokinetic model could be helpful in quantitatively describing the detailed processes of raltitrexed activity administered by HAI and determining an appropriate dosing regimen for preclinical and clinical studies.