leucovorin calcium / Generic mfg. - LARVOL DELTA

RASolute 302: Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P3 | N=501 | Active, not recruiting | Sponsor: Revolution Medicines, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Safety and feasibility of high dose methotrexate addition to R-CHOP chemotherapy for prophylaxis and treatment of secondary cns involvement by large B-cell lymphoma in a community-based hospital setting (ASH 2025) - "HDMTX is administered in a hospital setting with continuous intravenous fluids, urine alkalinization, drug level monitoring, and leucovorin rescue... Addition of HDMTX to R-CHOP for prophylaxis and treatment of SCNSL is feasible and safe in a community-based hospital setting. Clinical outcomes in our SCNSL cohort are similar to real-world reports from academic centers. Administering HDMTX prophylaxis concurrently with R-CHOP early in the course of treatment may minimize the risk of CNS relapse in high-risk LBCL patients."

Clinical • Acute Kidney Injury • B Cell Lymphoma • CNS Disorders • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mucositis • Nephrology • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Renal Disease • Secondary Central Nervous System Lymphoma

Impact of Neoadjuvant Chemotherapy on Perioperative Tumor Marker Dynamics and Postoperative Recovery in Patients Undergoing Laparoscopic Radical Resection for Rectal Cancer. (PubMed, J Gastrointest Cancer) - "Neoadjuvant chemotherapy prior to laparoscopic radical resection for rectal cancer was associated with improved anus preservation, enhanced postoperative recovery, and greater biochemical and functional benefits without increasing major complication rates, although it was linked to higher hematologic adverse events and postoperative declines in immune cell counts."

Biomarker • Journal • Retrospective data • Colorectal Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Rectal Cancer • Solid Tumor • CA 19-9 • CD4 • CD8

Surgery for Locally Advanced Pancreatic Cancer: Oncological Landmarks for Venous and Arterial Reconstruction. (PubMed, Ann Surg Oncol) - "We implement an extended neoadjuvant regimen-typically a minimum of eight cycles of FOLFIRINOX-aiming for normalization of CA19-9 levels...IMV, inferior mesenteric vein; LGV, left gastric vein; SMA, superior mesenteric artery artery; SV, splenic vein; SMV, superior mesenteric vein; RHA, right hepatic artery Prioritizing tumor biology, meticulous preoperative planning, and attention to key vascular technical details to ensure radical resection represent our three core oncologic landmarks. Further international, multicenter studies are needed to validate and promote the standardization of surgery for BR-PC and LAPC."

Journal • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9

HSV-1 infection as a rare trigger of methotrexate toxicity: A diagnostic and therapeutic challenge (ASH 2025) - "Four days earlier, she was seen in an outpatient clinic for a cold sore near the corner of her right lip and was prescribed valacyclovir 500 mg twice daily for three days for HSV infection. Her home medications included prednisone 2.5 mg, leucovorin 5 mg and methotrexate 12.5 mg weekly along with adalimumab 40 mg every 14 days...Intravenous hydrocortisone 50 mg twice daily was initiated...After a five-day course of IV steroids and a seven-day course of IV cefepime, she was discharged home on oral acyclovir to complete a 14-day total antiviral course... This case suggests that corticosteroids may be a valuable adjunct in patients with suspected methotrexate toxicity who do not respond to leucovorin. Further studies are needed to evaluate the role of corticosteroids in such cases."

Cardiovascular • Congestive Heart Failure • Diabetes • Endocrine Disorders • Febrile Neutropenia • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Herpes Simplex • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Neutropenia • Renal Disease • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis • Thrombocytopenia • Type 2 Diabetes Mellitus

Trilaciclib for the prevention of chemotherapy-induced myelosuppression: A systematic review and meta-analysis (ASH 2025) - "Chemotherapy regimens were heterogeneous and included etoposide-platinum (E/P) (either cisplatin or carboplatin) (n=5), gemcitabine/carboplatin (GCb) (n=2), topotecan (n=2), FOLFOXIRI (n=1), and Carboplatin/Paclitaxel/Tislelizumab (n=1)...It also showed a positive impact on progression-free and overall survival, without compromising chemotherapy effectiveness or increasing toxicity. These findings highlight Trilaciclib's potential as a valuable adjunct to chemotherapy in appropriately selected patients."

Retrospective data • Review • Breast Cancer • Colorectal Cancer • Febrile Neutropenia • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • Triple Negative Breast Cancer

Increased incidence of delayed methotrexate elimination in pediatric patients with Philadelphia-chromosome positive (Ph+) or ABL-class fusion positive (ABL-Class) acute lymphoblastic leukemia treated with imatinib: Results of a retrospective cohort study by the italian association of pediatric hematology-oncology (AIEOP) (ASH 2025) - P3 | "The two protocols had very similar supportive care guidelines for the managementof HDMTX: hyperhydration (3000 ml/m²/day) with sodium bicarbonate (100 mEq/m²/day) and folinic acidadministration (7.5 mg/m²/dose IV levo-product) at fixed time points (42h, 48h, and 54h post-infusion).Based on serum MTX levels measured at the time points (T24, T42, T48h post-infusion), hyperhydrationand folinic acid rescue could be modified by protocol... This is the largest currently available study reporting the clinical and pharmacologicaleffects of imatinib given during HDMTX. Our findings suggest that the concurrent administration ofimatinib during HDMTX is associated with an increased rate of mild to severe DME but does notsignificantly increase the incidence of typical HDMTX-related toxicities. Further prospective studies areneeded to determine whether a short discontinuation of imatinib during HDMTX may contribute to asafer HDMTX administration without..."

Retrospective data • Acute Kidney Injury • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Mucositis • Nephrology • Pediatrics • Renal Disease

Finding ferritin footprints in 5-fluorouracil-induced cardiotoxicity (ASH 2025) - "MethodsWe performed a retrospective chart review on patients aged 18 and older receiving 5-FU-basedintravenous chemotherapy (including 5-FU, FOLFOXIRI, FOLFIRI, FOLFIRINOX) at a single academic centerfrom June 1, 2022 to June 1, 2024...Should ferritin be elevated, we advise clinicians to maintaina high index of suspicion for obstructive CAD and heart failure. Larger multi-institutional studies onbiomarkers predicting cancer therapy-related cardiovascular toxicity or treatment failure rates meritfuture consideration."

Congestive Heart Failure • Coronary Artery Disease • Gastrointestinal Cancer • Heart Failure

Combination therapy with methotrexate, ifosfamide, cytarabine, dexamethasone and rituximab (R-MIAD) improves clinical outcomes in primary central nervous system lymphoma: A monocentric retrospective observational study (ASH 2025) - "The R-MIAD regimen was planned as: rituximab 375 mg/m² d0, MTX 3.5 g/m² d1 [for those >65 years old,partially discretionary to 3g/m2 depending on the general condition of the patient], ifosfamide (IFO) 1.5g/m² d2, cytarabine (HD-AraC) 2 g/m² d3, dexamethasone (DEX) 10 mg d1-3, every 21 days as 1 cycle.Calcium folinate salvage was started every 6 h for a total of 8 doses after 24 h of MTX administrationevery 6 h for a total of 8 times, while with regular monitoring of the blood MTX concentration of MTX.During ifosfamide administration, 300 mg/m² of mesna was administered simultaneously at time 0, 4hours, and 8 hours for urinary tract protection... Our results suggest that R-MIAD regimen is a feasible, safety-manageable, and effectivecombination therapy for patients with newly diagnosed PCNSL. Prospective clinical trials are still neededfor further verification of R-MIAD regimen in first-line treatment of PCNSL."

Clinical data • Combination therapy • Observational data • Retrospective data • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Thrombocytopenia • BCL6 • IRF4 • MME

Early methotrexate level thresholds predictive of acute kidney injury in patients with b cell lymphomas receiving high-dose methotrexate (ASH 2025) - "To our knowledge, this is the largest study to identify 2 AKI in pts receiving HD-MTX for B cell lymphoma. This challenges thenotion established by historical studies that time points prior 48 hours do not correlate with MTX-AKI.Use of higher MTX concentration thresholds and limiting cohort to those receiving similar durations ofMTX infusion in our study likely contributed to this finding. Earlier assessments of MTX levels may helpguide who most benefits from early supportive measures including more frequent Cr monitoring,adjustment of leucovorin dose, early glucarpidase administration, and/or MTX dose reduction forsubsequent cycles."

Clinical • Acute Kidney Injury • Acute Lymphocytic Leukemia • B Cell Lymphoma • CNS Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Renal Disease • Secondary Central Nervous System Lymphoma • Solid Tumor

CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis (ASH 2025) - "We hypothesized that by protecting HSPCs from the cytotoxic effects of chemotherapy,trilaciclib might also reduce the clonal expansion of TP53-mutant CH during chemotherapy.We obtained serial blood samples from healthy controls (n=176) and three placebo-controlledrandomized clinical trials of trilaciclib including patients with (1) SCLC (n=65) receiving carboplatin andetoposide, (2) metastatic colorectal cancer (mCRC) (n=125) receivingleucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) plus bevacizumab, and (3) metastatic triplenegative breast cancer (mTNBC) (n=34) receiving gemcitabine and carboplatin...Similar effectswere seen with the oral CDK4/6 inhibitor palbociclib and using a dominant negative form of CDK6introduced into p53 mutant HSPCs.Single cell RNA-seq of chimeric mice treated with carboplatin with trilaciclib or single agent controlsrevealed that CDK4/6 inhibition treatment promotes HSC and myeloid progenitor quiescence whilemitigating the myeloid..."

Breast Cancer • Colorectal Cancer • Eye Cancer • Hematological Malignancies • Lung Cancer • Retinal Disorders • Retinoblastoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • PTPRC • TP53

Outcomes in children and adolescents with down syndrome and B-lymphoblastic leukemia: A report from Children's oncology group study AALL1731 (ASH 2025) - "HR DS patients on AALL1131 received a chemotherapyregimen with DS-specific modifications: leucovorin rescue after intrathecal methotrexate (MTX), reducedinduction anthracycline, intermediate-dose MTX, and enhanced supportive care. Patients with DS and B-ALL continue to have inferior outcomes compared to those withoutDS due to both relapse and TRM. At a median follow-up of 4 years, DFS and OS on AALL1731 werepreserved but not improved compared to AALL1131 with use of 3 cycles of blinatumomab andmoderately de-intensified chemotherapy. However, the CI of relapse is significantly lower on AALL1731and to date, late relapses seen in previous cohorts of DS patients have not been observed."

Clinical • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia

Safety evaluation for less restrictive discharge criteria for patients receiving high dose methotrexate (ASH 2025) - "Patients received HD MTX alone or in combination with Cytarabine, R-CHOP, Blinatumomab, Vincristine or CODOX-M/IVAC... Our study shows that it is safe to discharge patients w/ MTX < 0.30 Umol/L compared to ourprior standard of 0.10 Umol/L or less with leucovorin and sodium bicarbonate for three days afterdischarge. Patients discharged early had stable renal function on discharge as well as on follow up labs,no difference in LFTs and no readmissions. While there was a higher incidence of cytopenias, it wasmostly grade 1 and 2 and did not result in treatment delays or other complications."

Clinical • Acute Kidney Injury • Acute Lymphocytic Leukemia • B Cell Lymphoma • Burkitt Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Renal Disease

Pembrolizumab and pralatrexate for relapsed or refractory peripheral T-cell lymphomas (ASH 2025) - "Supportive care, including leucovorin, was provided per institutional standards.Dose-limiting toxicities (DLTs) were defined as grade ≥4 hematologic or grade ≥3 non-hematologictreatment-related adverse events, with protocol-specified exceptions, occurring during the first twocycles of therapy. Furthermore,the ORR observed with this combination was lower than historical benchmarks for pralatrexatemonotherapy, which may be attributable to the reduced pralatrexate dosing in this study and potentialdirect growth stimulation of malignant T cells by pembrolizumab. Given the limited efficacy and safetyconcerns, further development of this regimen as studied is not warranted."

Cutaneous T-cell Lymphoma • Dermatology • Follicular Lymphoma • Hypertension • Lymphoma • Mycosis Fungoides • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Overall survival (OS) in patients with metastatic colorectal cancer (mCRC) following persistent chemotherapy-induced thrombocytopenia (pCIT) (ASH 2025) - "pCIT was defined as the first occurrence of a platelet countmeasurement ≤85×109/L, ≥13 days after the nearest prior chemotherapy administration with fluorouraciland oxaliplatin (FOLFOX) or fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI); or ≥ 20 days afteroxaliplatin and capecitabine (CAPOX)... The median OS for mCRC patients following the first pCIT ranges from 9.7 to 23.5 months,with 6-month survival probabilities between 64% and 90%, across different LOTs. Multiple factors, suchas LOT, ECOG, age, CIT grade, and bevacizumab use, are associated with clinically relevant differences insurvival in patients with pCIT. These findings provide clinically relevant benchmarks for survival and maybe useful in assessing the need for supportive therapy."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • Thrombocytopenia

Case Report: Successful Surgical Resection of PVTT Vp4 Hepatocellular Carcinoma Following Hepatic Arterial Infusion Chemotherapy Combined with Cadonilimab Plus Donafenib. (PubMed, Pharmgenomics Pers Med) - "Following multidisciplinary team evaluation, the patient received conversion therapy consisting of hepatic artery infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin, in combination with cadonilimab and donafenib...This regimen may substantially improve oncological outcomes and enable curative resection. This case provides compelling evidence to support further clinical investigation of this multimodal therapeutic combination."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • Thrombosis • AFP

A Study of GSK5764227 in Combination With Standard of Care (SoC) or Other Agents in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=72 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P1/2 trial • Oncology • Prostate Cancer • Solid Tumor

COLUMBIA 1: COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC (clinicaltrials.gov) - P1/2 | N=61 | Active, not recruiting | Sponsor: MedImmune LLC | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

Efficacy and safety of perioperative durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma in Asia: A subgroup analysis of the MATTERHORN trial (ESMO Asia 2025) - P3 | "Consistent with global MATTERHORN results, D + FLOT improved efficacy vs P + FLOT with a manageable safety profile in Asian pts with resectable G/GEJ adenocarcinoma."

Clinical • Gastroesophageal Junction Adenocarcinoma • Oncology

Synchronous Malignancy: Gastric Cancer and Cholangiocarcinoma (ESMO Asia 2025) - "Synchronous gastric adenocarcinoma and intrahepatic cholangiocarcinoma are exceptionally rare and present diagnostic and therapeutic challenges. This first Philippine case highlights the value of thorough histologic evaluation, molecular profiling, and a multidisciplinary approach in guiding individualized, patient-centered treatment."

Biliary Cancer • Cholangiocarcinoma • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • HER-2

Frequency of dihydropyrimidine dehydrogenase (DPD) deficiency in patients receiving fluoropyrimidine-based chemotherapy for solid tumors: A single-centre experience in Dubai, UAE (ESMO Asia 2025) - "Background: Dihydropyrimidine dehydrogenase (DPD) deficiency, caused by variants in the DPYD gene, is found in 3-5% of the population and significantly increases the risk of severe toxicity in patients receiving fluoropyrimidine chemotherapy such as 5-fluorouracil (5-FU)...The most frequently used regimens were CAPOX (n = 34, 33%), FOLFOX (n = 32, 31%), single-agent capecitabine (n = 18, 17%), FOLFIRINOX (n = 8, 8%), and FLOT (n = 5, 4%)... In our cohort, the prevalence of clinically significant DPYD mutations was lower than reported in global literature. These findings highlight the need for larger, region-specific studies to better understand DPYD variant frequencies in the Gulf region and to optimize individualized chemotherapy dosing."

Clinical • Colorectal Cancer • Oncology • Solid Tumor • DPYD

Physician choice multi-agent chemotherapy versus gemcitabine monotherapy for advanced pancreatic adenocarcinomas in frail or elderly patients - A randomized phase III clinical trial (ESMO Asia 2025) - "Background: Pancreatic ductal adenocarcinomas (PDAC) frequently present in an advanced unresectable stage (80-85%).Patients with ECOG PS 2 as well as elderly frail patients are underrepresented in trials evaluating advanced PDAC or patients who are not fit for intensive protocols like FOLFIRINOX...we wish to evaluate the benefit of giving a two-drug regimen in these patients versus administering only gemcitabine.Trial design: Phase III, Randomized, Open-label, parallel design, superiority study Histologically confirmed unresectable or metastatic adenocarcinoma of the pancreas or ampulla, with an ECOG PS 2 and age >/= 18 years OR Age >=70 with G8 screening score < 14 and intermediate/high risk on CARG score and adequate haematological, hepatic and renal function are randomized into one of two arms - Arm A (Physician choice multiagent chemotherapy) The treatment regimens allowed are 1.Gemcitabine 1000 mg/m2 IV plus Nab-paclitaxel 125 mg/m2 IV D1, D 8 and D15 q 28..."

Clinical • Metastases • Monotherapy • P3 data • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Real-world effectiveness of chemotherapy regimens in advanced pancreatic cancer: A nationwide, population-based cohort study in Taiwan (ESMO Asia 2025) - "Individuals receiving systemic chemotherapy within 90 days of diagnosis were categorized into treatment groups based on initial regimens: gemcitabine alone, gemcitabine plus nab-paclitaxel, S-1 alone, S-1 plus gemcitabine, FOLFIRINOX, GSL (gemcitabine plus S-1 plus leucovorin), 5-FU–based (5-FU with or without leucovorin), or other... This real-world study highlights the comparative effectiveness of chemotherapy regimens in APC and supports gemcitabine-based combinations as important options in East Asian clinical practice."

Clinical • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Donafenib, anti-PD-1 antibodies, plus HAIC as conversion therapy in patients with initially unresectable HCC:A prospective, single-arm, phase II study (ESMO Asia 2025) - P4 | "The triple combination of donafenib, anti-PD-1 antibodies, and HAIC exhibits favorable efficacy and tolerability, positioning it as a clinically feasible conversion strategy for initially unresectable HCC."

Clinical • P2 data • Hepatocellular Cancer • Oncology

FOLFOX-HAIC combined with sintilimab and donafenib for advanced hepatocellular carcinoma: A single-arm, phase II study (ESMO Asia 2025) - "The combination of mFOLFOX6-HAIC with sintilimab and donafenib exhibited an encouraging short-term efficacy for advanced HCC by improving the ORR and DCR, with acceptable toxicity. We will report more data in the future."

Metastases • P2 data • Hepatocellular Cancer • Oncology • Solid Tumor