Tomudex (raltitrexed) / Pfizer, AstraZeneca - LARVOL DELTA

Second-line raltitrexed plus irinotecan (SALIRI) with bevacizumab, cetuximab, or alone for metastatic colorectal cancer: a prospective multicenter cohort-based secondary analysis of the SALLY trial. (PubMed, J Gastrointest Oncol) - "The observed favorable outcomes in the SALIRI + Cet subgroup should be interpreted cautiously because of nonrandom treatment allocation. Future prospective, biomarker-driven and randomized studies are warranted to define the optimal clinical positioning of SALIRI-based combinations."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Conversion therapy with Tislelizumab plus Gemcitabine and Cisplatin (GemCis) combined with Hepatic Arterial Infusion Chemotherapy (HAIC) using Raltitrexed for locally advanced unresectable intrahepatic cholangiocarcinoma: A phase II, single-arm, prospective study. (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Synchronous multiple primary colorectal cancer with discordant RAS status between primary lesions: a case report in an elderly patient. (PubMed, Front Surg) - "Given the patient's advanced age and intolerance to standard chemotherapy, a staged, multimodal integrated strategy was adopted: synchronous surgery for three primary lesions, minimally invasive ESD of the transverse colon lesion, artificial ascites-assisted percutaneous microwave ablation (AA-MWA) for liver metastases, and individualized adjustment of chemotherapy (switched from CAPEOX to oxaliplatin plus raltitrexed because of intolerance). This case demonstrates that primary lesions in SMPCRC can harbor substantial molecular heterogeneity, such that single-lesion testing may be insufficient to guide treatment decisions in complex scenarios. For elderly patients intolerant to standard regimens, a staged, multimodal integrated approach (synchronous surgery + ESD + AA-MWA + individualized chemotherapy adjustment) may serve as a feasible comprehensive treatment option."

Journal • Colon Cancer • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CEACAM5 • KRAS • NRAS • PIK3CA

Radiation-Associated Small Intestinal Angiosarcoma Presenting as Small Bowel Obstruction in a Gastric Cancer Survivor (ACG 2026) - "She received 6 cycles of neoadjuvant SOX (S-1 plus oxaliplatin) followed by total gastrectomy in October 2017 and subsequent adjuvant oral S-1. In November 2017 the disease progressed with enlargement of retroperitoneal nodes; she received 6 cycles of paclitaxel plus raltitrexed, then concurrent S-1 and volumetric modulated arc therapy (VMAT; 50 Gy in 25 fractions to the retroperitoneal region) in 2018, followed by oral apatinib until 2019...(C) MYC: nuclear positivity in approximately 20â30% of tumor cells, supporting a radiation-associated origin. (D) Ki-67: elevated proliferation index (approximately 30â40%), consistent with a high-grade, highly proliferative tumor."

Angiosarcoma • Cachexia • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Disorder • Oncology • Sarcoma • Solid Tumor • CD31 • MYC • PECAM1

Specificity of the Interactions of Folate-Based Vectors with Folate Receptor-α. (PubMed, J Phys Chem B) - "The study explores the molecular-level binding of a set of vector ligands─folate, methotrexate, raltitrexed, pemetrexed, 5-methyltetrahydrofolate, and pteroyl ornithine─to the membrane-embedded folate receptor-α, a relevant target in cancer therapy. On the basis of the performed analyses, general guidelines for ligands to bind to the active site of the protein are formulated. Among the addressed ligands, only folate and raltitrexed comply with the requirements and bind sustainably to the receptor active site, outlining them as effective vectors for folate-based drug-delivery systems."

Journal • Oncology • FOLR1

Patient-Derived Organoid and Single-Cell Multiomics Reveal Evolution Driven by CEACAM6/KRT19-Mediated Heterogeneity. (PubMed, FASEB J) - "To dissect chemoresistance mechanisms, six organoids representing extreme phenotypes (three sensitive and three resistant, based on IC50 difference for irinotecan + raltitrexed) were selected from this cohort for single-cell transcriptomic analysis. Our multi-omics framework establishes organoid-guided chemoresistance mechanisms while proposing ITH quantification targeting as precision strategies. This study bridges critical gaps in CRC therapeutic personalization, offering clinically actionable insights for overcoming treatment failure."

Heterogeneity • Journal • Colorectal Cancer • Oncology • Solid Tumor • CEACAM6 • KRT18 • KRT18 • KRT19 • TFF1 • TFF3

A Phase II Clinical Trial of Chemotherapy Rechallenge with or without Targeted Therapy in Refractory Metastatic Colorectal Cancer. (PubMed, Oncol Res) - "Patients received rechallenge chemotherapy (oxaliplatin-, irinotecan-, or raltitrexed-based) with or without targeted agents (bevacizumab or cetuximab). Grade 3 or 4 adverse events were reported in 39.5% of patients, with no severe adverse events or treatment-related deaths observed. Chemotherapy rechallenge strategies, particularly when combined with targeted agents, demonstrated promising clinical activity and acceptable safety in selected heavily pretreated patients with mCRC who previously achieved sustained disease control."

Journal • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Modified iTACE combined with atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma: A prospective single-center study (ESMO-GI 2026) - "Here we report results of modified iTACE (TACE plus HAIC with raltitrexed and oxaliplatin [HAICROX]) combined with atezo+bev in uHCC.Methods This prospective study enrolled 69 patients (pts) with CNLC stage IIb-IIIb uHCC and Child-Pugh A liver function at Fudan University Shanghai Cancer Center (Nov 2022-Jan 2026). Grade 3+ AEs occurred in 14.5%, including thrombocytopenia (n=3), islet function loss (n=1), myasthenia gravis (n=1), hypertensive crisis (n=1), ketoacidosis (n=1), severe hypothyroidism (n=1), GI perforation (n=1) and GI bleeding (n=2, 1 fatal).Conclusions Modified iTACE combined with atezo+bev demonstrated encouraging anti-tumor activity (ORR 78.2%), conversion potential (13.0%) and a manageable safety profile in uHCC. These findings warrant validation in multicenter controlled studies."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Case Report: Exchange transfusion for hemolytic anemia and acute kidney injury associated with hepatic arterial infusion chemotherapy with raltitrexed and oxaliplatin in a patient with hepatocellular carcinoma. (PubMed, Front Med (Lausanne)) - "In this report, we present a case of severe hemolytic anemia and acute kidney injury in a patient with hepatocellular carcinoma after hepatic arterial infusion chemotherapy with raltitrexed plus oxaliplatin therapy, which was suspected to be oxaliplatin-related. The patient achieved complete clinical resolution through two personalized sessions of exchange transfusion, supplemented with artificial liver support therapy."

Journal • Acute Kidney Injury • Anemia • Colorectal Cancer • Hematological Disorders • Hepatocellular Cancer • Nephrology • Oncology • Renal Disease • Solid Tumor

Thymidylate synthase inhibitory drugs induce p53-dependent pathways differently. (PubMed, PLoS One) - "Thymidylate synthase (TS) is a key enzyme in thymidylate biosynthesis and an established target of chemotherapeutics such as 5-fluoro-2'-deoxyuridine (5FdUR) and raltitrexed (RTX)...Moreover, co-immunoprecipitation coupled to sequencing revealed direct RNA partners of TS, highlighting its possible post-transcriptional regulatory role. Our findings underscore the multifaceted impact of TS inhibition, linking enzymatic disruption to RNA-level regulation and revealing drug-specific differences in cellular responses."

Journal • MYC • TYMS

TACE Combined with Ralox-HAIC (Oxaliplatin Puls Raltitrexed) and System Therapy in Patients with Unresectable Hepatocellular Carcinoma. (PubMed, J Hepatocell Carcinoma) - "No Grade 4 treatment-related adverse events or treatment-related deaths occurred. TACE combined with Ralox-HAIC and systemic therapy demonstrated a high ORR and DCR with manageable safety in uHCC, warranting further prospective studies for validation."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Metronomic Capecitabine Triggers Ferroptosis in Hepatocellular Carcinoma Cells Through Inhibition of TYMS. (PubMed, Cancer Med) - "CAP targets TYMS to induce ferroptosis by activating NOX, thereby inhibiting HCC progression."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • TYMS

Raltitrexed in Hepatocellular Carcinoma: Mechanistic Rationale and Clinical Evidence from Arterial-Based Therapies. (PubMed, J Hepatocell Carcinoma) - "Compared with 5-fluorouracil, raltitrexed offers distinct pharmacokinetic and practical advantages, including prolonged intracellular retention and a short infusion schedule...Accumulating evidence from retrospective studies, prospective single-arm trials, and limited comparative analyses suggests that raltitrexed-based regimens demonstrate meaningful antitumor activity in conventional and drug-eluting bead TACE, as well as in oxaliplatin-based HAIC, with objective response rates, disease control, and survival outcomes comparable to established chemotherapy protocols...Overall, raltitrexed represents a rational and increasingly utilized component of arterial-based therapies for unresectable HCC. However, current evidence is predominantly derived from retrospective and single-arm studies, and well-designed randomized trials and biomarker-driven approaches are required to define its optimal role in clinical practice."

IO biomarker • Journal • Review • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TYMS

Effect and safety analysis of raltitrexed peritoneal perfusion in patients with intermediate and advanced colorectal cancer. (PubMed, Oncol Lett) - "In conclusion, raltitrexed peritoneal infusion chemotherapy is effective and safe for the treatment of patients with intermediate and advanced CC; it can effectively reduce serum tumour marker levels and adverse reaction incidence and improve the survival quality of patients. Raltitrexed peritoneal infusion chemotherapy thus exhibits high clinical application value."

Journal • Colorectal Cancer • Embryonal Tumor • Oncology • Solid Tumor • CA 19-9 • CEACAM5

A Prospective, Single-Arm Study of Nimotuzumab plus Camrelizumab, Irinotecan Liposome (II) and Raltitrexed as First-Line Treatment for Locally Advanced or Metastatic Pancreatic Cancer (ChiCTR) - P=N/A | N=42 | Sponsor: Chongqing Medical University First Affiliated Hospital; Chongqing Medical University First Affiliated Hospital

New trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Real-World Study of anti-PD-1 Combined with Regorafenib and Raltitrexed as Third-Line Therapy in Colorectal Cancer. (PubMed, J Gastrointest Cancer) - No abstract available

Journal • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor

Simultaneous analysis of various anticancer drugs by supercritical fluid chromatography-mass spectrometry. Part II: Method validation and comparison with liquid chromatography. (PubMed, J Pharm Biomed Anal) - "The selected drugs were the following: 5-fluorouracil, azacitidine, busulfan, carboplatin, cisplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, mitomycin, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine and vincristine. Furthermore, although the developed SFC-MS/MS method was characterized by a lower sensitivity, it allowed the quantification of compounds that were difficult to analyze by UHPLC-MS/MS, such as azacitidine and cisplatin, with analytical performance comparable to that obtained for the other CADs analyzed. This feature highlights the complementarity of the two chromatographic approaches in the context of CAD determination in a hospital environment."

Journal • Oncology

Hyperthermic intraperitoneal chemotherapy with raltitrexed for peritoneal recurrence presenting with massive ascites following radical surgery for advanced gastric cancer: a case report. (PubMed, Front Oncol) - "The patient experienced significant clinical improvement, characterized by the resolution of ascites, alleviation of symptoms, and prolonged survival, thereby creating an opportunity for subsequent comprehensive treatment. It is hoped that this case can provide a treatment option for patients with peritoneal recurrence after radical gastrectomy for GC."

Journal • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor

A short-term, exploratory randomized controlled trial on the safety and feasibility of intraoperative raltitrexed peritoneal chemotherapy in laparoscopic radical resection for advanced colorectal cancer. (PubMed, Front Surg) - "For patients with advanced CRC (T3/T4), laparoscopic radical resection combined with intraoperative raltitrexed IPC is feasible and exhibits an acceptable short-term safety profile. Observed short-term changes in tumor markers are considered exploratory findings and require validation in subsequent, large-scale prospective studies with extended follow-up periods."

Journal • Colorectal Cancer • Hematological Disorders • Oncology • Solid Tumor • CA 19-9 • CEACAM5

ECOG 6293: Phase II Study of Raltitrexed in Advanced Colorectal Cancer. (PubMed, Oncologist) - "In this phase II trial, raltitrexed did not show significant response rates in patients with advanced CRC. Due to limited ORR of raltitrexed, value of TS expression as a biomarker was inconclusive. No new safety signals for raltitrexed were demonstrated."

Journal • P2 data • Colorectal Cancer • Oncology • Solid Tumor • TYMS

Chromobox2 inhibition: a novel activity of alisertib, an aurora A kinase inhibitor. (PubMed, Mol Cancer Ther) - "In vitro validation narrowed compounds of interest to raltitrexed, alisertib, GTX-007, LY315920, and PD0325901. Treatment with alisertib leads to decrease in H2AK119ub and shift in the immune tumor microenvironment. Alisertib efficacy in HGSC is dependent on functional CBX2 and cell target engagement confirms selectivity for CBX2, supporting that alisertib activity involves CBX2 inhibition."

Journal • Oncology • AURKA • CBX2

Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential. (PubMed, Life Sci Alliance) - "Previously, we established that treating HCT116 colon cancer cell lines with either raltitrexed (RTX) or 5-fluoro-2'-deoxyuridine (5FdUR), two potent inhibitors of thymidylate synthase, results in characteristic genomic uracil patterns...The mutational spectra and the clustered nature of these transitions suggested the involvement of APOBEC3 DNA cytidine deaminases, several of which were induced under these conditions. Notably, this mutagenic response coincides with decreased cytotoxicity compared with the low-dose 5FdUR or any efficient doses of RTX, providing insights that may be relevant for personalized cancer therapy."

Journal • Colon Cancer • Oncology • Solid Tumor • TYMS

A Prospective, Safety, and Efficacy Clinical Trial of Pressurized Intraperitoneal Aerosol Therapy for Peritoneal Metastasis of Colorectal Cancer (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor

Design, Synthesis, and Anticancer Assessment of Benzylated Pyrrole-Based Pyrido[2,3-d]Pyrimidines as Thymidylate Synthase Inhibitors. (PubMed, Chem Biol Drug Des) - "Compounds 1c and 2i exhibited potent TS inhibition with IC50 values of 11.50 ± 1.08 nM and 17.12 ± 0.91 nM, respectively, comparable to the standard drug raltitrexed (IC50 = 12.51 ± 0.91 nM)...Additionally, compounds 1c and 2i exhibited good stability in 300 ns molecular dynamics simulations along with acceptable drug-like properties and oral bioavailability. These findings suggest that compounds 1c and 2i are promising lead candidates for the development of TS inhibitors."

Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TYMS

The BEVATOMOX phase II trial: raltitrexed/oxaliplatin/bevacizumab vs mFOLFOX6/bevacizumab in 2nd-line metastatic colorectal cancer. (PubMed, Oncologist) - P2 | "The TOMOX-Bev combination is a feasible second-line mCRC treatment with an acceptable toxicity profile. Recruitment failure prevents efficacy conclusions, but TOMOX-Bev may be an alternative if fluropyrimidines are contraindicated."

Journal • P2 data • Colorectal Cancer • Dermatology • Febrile Neutropenia • Hematological Disorders • Mucositis • Neutropenia • Oncology • Solid Tumor • KRAS