Skip to main content
WoMWeb of Medicine
SearchGraphHistory
Oncology›Condition·Updated Apr 22, 2026·v1

Sorafenib

Sorafenib is an oral multikinase inhibitor used for advanced hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma. It works by inhibiting tumor growth and blood supply. Key management involves monitoring for hand-foot skin reactions, hypertension, and liver function, with specific dose reductions required for toxicity.

High Evidence88 references·3,873 words·16 min read·v1
oncologyhepatologytyrosine kinase inhibitorHCCRCC

Quick Reference

RxDrug of choiceFirst-line systemic therapy for unresectable HCC (Child-Pugh A) and RAI-refractory DTC.
AltAlternativesLenvatinib, Atezolizumab/Bevacizumab (HCC); Sunitinib, Pazopanib (RCC); Lenvatinib (DTC).
⊘AvoidSquamous cell lung cancer (when used with carboplatin/paclitaxel); severe hypersensitivity.
DxTest of choiceChild-Pugh Score (for HCC eligibility); Baseline ECG (for QTc).
ScKey scoreChild-Pugh Class A (required for optimal safety/efficacy in HCC).
→When to referRefer for Grade 3/4 hypertension, cardiac ischemia, GI perforation, or severe DILI.
Sorafenib is a foundational oral multikinase inhibitor for HCC, RCC, and DTC, requiring careful monitoring for skin toxicity and hypertension.
Sorafenib is an oral multikinase inhibitor that revolutionized the treatment of advanced [[hepatocellular carcinoma]] (HCC), becoming the first systemic agent to demonstrate a significant survival benefit in unresectable liver cancer. It exerts a dual mechanism of action by inhibiting the Raf/MEK/ERK signaling pathway to suppress tumor cell proliferation and targeting receptor tyrosine kinases (VEGFR and PDGFR) to disrupt tumor [[angiogenesis]]. Beyond HCC, sorafenib is a standard therapy for advanced [[renal cell carcinoma]] (RCC) and radioactive iodine-refractory [[differentiated thyroid carcinoma]] (DTC). While newer immunotherapy combinations have emerged as first-line options, sorafenib remains a global benchmark and a vital alternative for patients with contraindications to immune checkpoint inhibitors. Its clinical use is characterized by a manageable but distinct toxicity profile, including [[hand-foot skin reaction]], diarrhea, and [[hypertension]], which requires proactive monitoring and stepwise dose titration.

Overview and Recommendations

Key Facts

  • •Recognize sorafenib as a pioneering biaryl urea multikinase inhibitor that targets both the intracellular Raf serine/threonine kinases (CRAF, BRAF, and mutant BRAF) and cell surface receptor tyrosine kinases (VEGFR-1, -2, -3, PDGFR-beta, KIT, and FLT-3).
  • •Identify the primary clinical indications: unresectable (HCC), advanced (RCC), and locally recurrent or metastatic (DTC) that is refractory to radioactive iodine treatment.
  • •Understand the landmark clinical impact established by the SHARP trial, which demonstrated that sorafenib extended median overall survival in HCC patients with preserved liver function, specifically those classified as Class A.
  • •Note the emerging role of sorafenib as maintenance therapy in FLT3-mutated (AML) following allogeneic hematopoietic cell transplantation to reduce the risk of relapse.
  • •Consider the pharmacokinetic profile, which features a mean elimination half-life of 25 to 48 hours and primary hepatic metabolism via and , necessitating caution with strong enzyme inducers or inhibitors.

Clinical Use

  • •Suspect the need for sorafenib in patients with advanced solid tumors that have progressed beyond surgical or locoregional options, particularly hypervascular malignancies like HCC and RCC.
  • •Assess liver function rigorously before initiation using the ; sorafenib is primarily validated for Class A patients, as safety in Class B or C is less established and carries a higher risk of toxicity.
  • •Obtain baseline laboratory studies including a complete blood count (CBC), liver function tests (ALT, AST, bilirubin), serum lipase, and amylase to monitor for drug-induced elevations or asymptomatic pancreatitis.
  • •Screen for cardiovascular risk factors and obtain a baseline electrocardiogram (ECG) to evaluate the , as sorafenib can cause modest QTc prolongation (mean increase of 8.5 ms).
  • •Monitor blood pressure weekly during the first 6 weeks of therapy to detect early-onset , a common class effect of VEGF inhibition.
  • •Evaluate for the presence of esophageal varices in HCC patients prior to starting therapy, as the risk of hemorrhage may be elevated in the setting of portal hypertension.
  • •Perform a baseline dermatologic exam of the palms and soles to prepare for the monitoring of (HFSR), which typically appears within the first six weeks of treatment.
  • •Verify pregnancy status in females of reproductive potential, as sorafenib is highly teratogenic and requires strict adherence to effective .
  • •Review the patient's current medication list for strong CYP3A4 inducers like rifampin or anticonvulsants, which can significantly decrease sorafenib exposure and efficacy.
  • •Order an International Normalized Ratio (INR) at baseline and regularly thereafter for patients taking concomitant , as sorafenib can increase the risk of clinical bleeding and INR fluctuations.

Safety

  • •Administer sorafenib at the standard starting dose of 400 mg (two 200 mg tablets) orally twice daily, ensuring the patient takes it on an empty stomach (1 hour before or 2 hours after a meal).
  • •Avoid high-fat meals during administration, as they can reduce the bioavailability of the drug by approximately 29% compared to the fasted state.
  • •Implement a stepwise dose reduction for toxicity in HCC or RCC: first decrease to 400 mg once daily, then to 200 mg once daily or 400 mg every other day if symptoms persist.
  • •Utilize a three-step reduction for DTC: first to 600 mg daily (400 mg morning/200 mg evening), then to 200 mg twice daily, and finally to 200 mg once daily.
  • •Manage (HFSR) by using urea-based creams and topical steroids; for Grade 2 or 3 reactions, interrupt therapy until symptoms resolve to Grade 0-1, then resume at a reduced dose.
  • •Attempt dose re-escalation for dermatologic toxicity if the patient remains stable at a reduced dose for at least 28 days; approximately 50% of patients will tolerate the higher dose upon resumption.
  • •Treat diarrhea, the most common gastrointestinal side effect (55%), promptly with anti-diarrheal agents like loperamide to prevent dehydration and electrolyte imbalances.
  • •Discontinue sorafenib permanently if the patient develops perforation, Grade 4 hypertension, or Grade 2 or higher cardiac ischemia/infarction.
  • •Monitor for (DILI) and stop therapy if AST or ALT levels exceed 5 times the upper limit of normal or if bilirubin increases significantly in a hepatocellular pattern.
  • •Interrupt therapy at least 10 days prior to major elective surgery to minimize the risk of impaired wound healing and perioperative bleeding.
  • •Advise females to use effective contraception during treatment and for 6 months after the final dose; males with partners of reproductive potential should use contraception for 3 months post-treatment.
  • •Contraindicate the use of sorafenib in combination with carboplatin and paclitaxel for patients with squamous cell lung cancer due to an observed increase in mortality.
  • •Avoid breastfeeding during therapy and for at least 2 weeks following the last dose due to the potential for serious adverse reactions in the infant.
  • •Refer patients to a specialist if they develop unstable angina or congestive heart failure, as these require immediate cessation of the drug.
  • •Monitor lipase levels regularly; while asymptomatic elevations are common, clinical pancreatitis (occurring in <1% of patients) requires treatment interruption.

Board Review — High Yield

  • •Hand-foot skin reaction (HFSR) — A hallmark side effect of sorafenib, localized to high-pressure areas of palms/soles, distinct from the diffuse hand-foot syndrome of 5-FU.
  • •Mechanism of Action — Dual inhibition of Raf kinases (proliferation) and VEGFR/PDGFR (angiogenesis).
  • •SHARP Trial — The landmark study that established sorafenib as the first systemic agent to improve survival in advanced HCC.
  • •Squamous Cell Lung Cancer — Sorafenib is contraindicated in this population when combined with carboplatin/paclitaxel due to increased mortality.
  • •Empty Stomach — Must be taken 1 hour before or 2 hours after meals to avoid decreased bioavailability from high-fat food.
  • •QTc Prolongation — A known pharmacodynamic effect; requires monitoring, especially if used with other QT-prolonging drugs.
  • •Dose Modification — Stepwise reduction (e.g., 400mg BID to 400mg QD) is the primary strategy for managing Grade 2/3 toxicities.

Deep Dive — Evidence Details

References

  1. [1]

    Shi Y, Han G, Zhou J et al.. “Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial.” The lancet. Gastroenterology & hepatology (2025). PMID: 40409323 ↗

    L1RCTCited in: Introduction and Chemical Structure, Indications and Clinical Use
  2. [2]

    Zhen S. “High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay.” Journal of medical virology (2025). PMID: 40400495 ↗

    L5REVIEW_NARRATIVECited in: Introduction and Chemical Structure
  3. [3]

    Kennedy VE, Touya M, Spalding J et al.. “Real-world treatment adherence and persistence of FLT3 inhibitors as post-alloHCT maintenance therapy in patients with AML in the United States: a cohort study using administrative claims data.” Leukemia & lymphoma (2025). PMID: 41041900 ↗

    L2COHORTCited in: Introduction and Chemical Structure
  4. [4]

    Sun M, Mao H, Luo Y et al.. “Multi-Omics and Machine Learning-Uncovered FLT1-Mediated Epithelial-Endothelial Crosstalk in Cellular Senescence Driving Clear Cell Renal Cell Carcinoma Malignancy.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2026). PMID: 41999263 ↗

    L5OTHERCited in: Introduction and Chemical Structure
  5. [5]

    Soliman AM, Khalil A, Ghorab MM. “Novel methoxyquinazoline sulfonamide derivatives as angiogenesis inhibitors and radiosensitizers.” European journal of medicinal chemistry (2026). PMID: 41936795 ↗

    L5OTHERCited in: Introduction and Chemical Structure, Dose and Administration, Dose Modification
  6. [6]

    Li TZ, Li FJ, Hu MM et al.. “Synthesis and discovery of guaianolide - eudesmanolide heterodimers as CDK2 inhibitors for the treatment of hepatocellular carcinoma.” European journal of medicinal chemistry (2026). PMID: 41344115 ↗

    L5OTHERCited in: Introduction and Chemical Structure, Dose and Administration, Dose Modification
  7. [7]

    Aref MMA, Abdallah AE, Dahab MA et al.. “Design, synthesis, anticancer evaluation, biological screening, and computational study of novel 6,7-dimethoxyquinazoline derivatives as VEGFR-2 inhibitors and apoptotic inducers.” European journal of medicinal chemistry (2026). PMID: 41014811 ↗

    L5OTHERCited in: Introduction and Chemical Structure, Dose and Administration, Dose Modification
  8. [8]

    Luce A, Bocchetti M, Cossu AM et al.. “Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.” Journal of translational medicine (2025). PMID: 40993657 ↗

    L5OTHERCited in: Introduction and Chemical Structure
  9. [9]

    Vishwa R, Sailo BL, BharathwajChetty B et al.. “Enhancing Anticancer Treatment Efficacy With Lycopene: A Comprehensive Review of Clinical and Preclinical Evidence.” Journal of biochemical and molecular toxicology (2025). PMID: 41140031 ↗

    L1SR_OBSCited in: Mechanism of Action
  10. [10]

    Su P, Yang Y, Zheng H. “The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.” Frontiers in immunology (2026). PMID: 41816347 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  11. [11]

    Elmetwalli A. “Ferroptosis and the cGAS-STING pathway into precision nano-immuno-theranostics: A mechanistic paradigm for reversing drug resistance in hepatocellular carcinoma.” Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy (2026). PMID: 41275854 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  12. [12]

    Yang Y, Zhao P, Chen H et al.. “Novel Strategies against Hepatocellular Carcinoma through Lipid Metabolism.” Oncology research (2025). PMID: 41179299 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  13. [13]

    Zhao L, Cheng J, Zheng Y et al.. “Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.” International journal of cancer (2026). PMID: 40818043 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  14. [14]

    Yousef EH, El Gayar AM, El-Magd NFA. “Insights into Sorafenib resistance in hepatocellular carcinoma: Mechanisms and therapeutic aspects.” Critical reviews in oncology/hematology (2025). PMID: 40389183 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  15. [15]

    Carvalho MJ, Santos F, Vieira V et al.. “Targeting endometrial stem cell in endometriosis treatment, a scoping review.” Journal of gynecology obstetrics and human reproduction (2026). PMID: 41570918 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  16. [16]

    Ahmed EA. “The Potential Therapeutic Role of Beta-Caryophyllene as a Chemosensitizer and an Inhibitor of Angiogenesis in Cancer.” Molecules (Basel, Switzerland) (2025). PMID: 40333803 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action, Drug Interactions
  17. [17]

    Wang Z, Su X, Zhan Z et al.. “miR-660: A novel regulator in human cancer pathogenesis and therapeutic implications.” Gene (2025). PMID: 40120868 ↗

    L5REVIEW_NARRATIVECited in: Mechanism of Action
  18. [18]

    Wu Y, Ju G, Zhou X et al.. “Targeting WTAP sensitizes hepatocellular carcinoma to sorafenib by inhibiting the ERK signaling pathway.” Journal of Zhejiang University. Science. B (2026). PMID: 41847736 ↗

    L5OTHERCited in: Mechanism of Action
  19. [19]

    Chen SX, Qi X, Zheng XT et al.. “LCN2 aggravates sepsis-induced ALI by inhibiting MUC1 to activate ER-stress-autophagy induced ferroptosis via lactate/MCT1/AMPK/mTOR axis.” Apoptosis : an international journal on programmed cell death (2026). PMID: 41838195 ↗

    L5OTHERCited in: Mechanism of Action
  20. [20]

    Sen S, Duong VT, Hwang Y et al.. “COPG1 Is a Selectively Essential Regulator of Cancer Progression and Chemoresistance via Redox Modulation and AKT Signaling.” International journal of molecular sciences (2026). PMID: 41751842 ↗

    L5OTHERCited in: Mechanism of Action
  21. [21]

    Zhao Y, Zhang X, Ding X et al.. “Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials.” Frontiers in pharmacology (2024). PMID: 38828446 ↗

    L1TRIAL_NONRANDOMCited in: Pharmacokinetics (LADME)
  22. [22]

    Song S, Bai M, Li X et al.. “Early predictive value of circulating biomarkers for sorafenib in advanced hepatocellular carcinoma.” Expert review of molecular diagnostics (2022). PMID: 35234564 ↗

    L5SR_OBSCited in: Pharmacokinetics (LADME)
  23. [23]

    Lennernäs H, Brisander M, Liljebris C et al.. “Enhanced Bioavailability and Reduced Variability of Dasatinib and Sorafenib with a Novel Amorphous Solid Dispersion Technology Platform.” Clinical pharmacology in drug development (2024). PMID: 38808617 ↗

    L2RCTCited in: Pharmacokinetics (LADME)
  24. [24]

    Cheng Z, Wei-Qi J, Jin D. “New insights on sorafenib resistance in liver cancer with correlation of individualized therapy.” Biochimica et biophysica acta. Reviews on cancer (2020). PMID: 32522600 ↗

    L5REVIEW_NARRATIVECited in: Pharmacokinetics (LADME)
  25. [25]

    Swm AM, Mita SR, Husni P. “Spray Drying for Pharmaceutical Raw Materials: A Systematic Review on Enhancing Bioavailability and Stability.” Drug design, development and therapy (2025). PMID: 41458252 ↗

    L1SR_OBSCited in: Pharmacokinetics (LADME)
  26. [26]

    Chaurawal N, Estrada AR, Pors K et al.. “Innovative Nanocarriers of Sorafenib in the Optimisation of Therapeutic Outcome: Challenges and Applications in Breast Cancer.” AAPS PharmSciTech (2026). PMID: 41857404 ↗

    L5REVIEW_NARRATIVECited in: Pharmacokinetics (LADME)
  27. [27]

    Mateen A, Khan A, Khan I et al.. “Formulation development, characterization, and evaluation of sorafenib-loaded PLGA-chitosan nanoparticles.” Frontiers in pharmacology (2024). PMID: 39444599 ↗

    L5OTHERCited in: Pharmacokinetics (LADME)
  28. [28]

    Li Z, Kim W, Utturkar S et al.. “DDX5 deficiency drives non-canonical NF-κB activation and NRF2 expression, influencing sorafenib response and hepatocellular carcinoma progression.” Cell death & disease (2024). PMID: 39122708 ↗

    L5OTHERCited in: Pharmacokinetics (LADME)
  29. [29]

    Wang Q, Sun X, Fang X et al.. “Dual-molecular targeting nanomedicine upregulates synergistic therapeutic efficacy in preclinical hepatoma models.” Acta biomaterialia (2024). PMID: 38838902 ↗

    L5OTHERCited in: Pharmacokinetics (LADME)
  30. [30]

    Kim YJ, Lim B, Kim SY et al.. “Remodeling of sorafenib as an orally bioavailable ferroptosis inducer for Lung Cancer by chemical modification of adenine-binding motif.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2024). PMID: 38796972 ↗

    L5OTHERCited in: Pharmacokinetics (LADME)
  31. [31]

    Jia XM, Hao H, Zhang Q et al.. “The bioavailability enhancement and insight into the action mechanism of poorly soluble natural compounds from co-crystals preparation: Oridonin as an example.” Phytomedicine : international journal of phytotherapy and phytopharmacology (2024). PMID: 37925890 ↗

    L5OTHERCited in: Pharmacokinetics (LADME)
  32. [32]

    Yu Y, Shen X, Xiao X et al.. “Butyrate Modification Promotes Intestinal Absorption and Hepatic Cancer Cells Targeting of Ferroptosis Inducer Loaded Nanoparticle for Enhanced Hepatocellular Carcinoma Therapy.” Small (Weinheim an der Bergstrasse, Germany) (2023). PMID: 37165608 ↗

    L5OTHERCited in: Pharmacokinetics (LADME)
  33. [33]

    Peng TR, Huang YH, Wu TW et al.. “Comparative efficacy of immune checkpoint inhibitor-based regimens versus tyrosine kinase inhibitors in advanced hepatocellular carcinoma stratified by etiology: a systematic review and meta-analysis.” International journal of clinical oncology (2026). PMID: 41701457 ↗

    L1SR_OBSCited in: Pharmacodynamics, Adverse Effects and Toxicity
  34. [34]

    Li Q, Li H, Ma H et al.. “Efficacy and safety of first-line immunotherapy and targeted therapy in advanced HCC: a network meta-analysis with subgroup analysis based on HBV and HCV infection.” Frontiers in immunology (2026). PMID: 41694404 ↗

    L1SR_OBSCited in: Pharmacodynamics, Adverse Effects and Toxicity
  35. [35]

    Qi H, Huang Y, Zhang W et al.. “Immune checkpoint inhibitor-based first-line therapies for advanced or unresectable hepatocellular carcinoma: a network meta-analysis and cost-effectiveness analysis.” Therapeutic advances in medical oncology (2026). PMID: 41804358 ↗

    L1SR_OBSCited in: Pharmacodynamics
  36. [36]

    Michelon I, do Rêgo Castro CE, Querino Belluco AP et al.. “Multi-Targeted TKIs in Patients with Advanced Ewing Sarcoma: A Systematic Review and Single-Arm Meta-Analysis.” Cancers (2026). PMID: 41681938 ↗

    L2SR_OBSCited in: Pharmacodynamics, Adverse Effects and Toxicity
  37. [37]

    Cho Y, Lee JH, Ryoo BY et al.. “Second-Line and Subsequent Therapies after Atezolizumab Plus Bevacizumab Treatment in Hepatocellular Carcinoma: A Multicenter Prospective Cohort Study.” Gut and liver (2026). PMID: 41944032 ↗

    L2COHORTCited in: Pharmacodynamics
  38. [38]

    Sherazi AW, Rasool MF, Jiao Z et al.. “A systematic review on clinical pharmacokinetics and pharmacodynamics of antiangiogenic tyrosine kinase inhibitors (TKIs) with high TDM scores.” Expert review of anticancer therapy (2026). PMID: 41947705 ↗

    L2SR_OBSCited in: Pharmacodynamics
  39. [39]

    Bruzzese A, Lofaro D, Martino EA et al.. “Comparative efficacy of different therapeutic approaches in treatment naïve FLT3-mutated AML eligible for intensive chemotherapy: a Bayesian network meta-analysis of randomized trials.” Annals of hematology (2026). PMID: 41940985 ↗

    L1SR_OBSCited in: Pharmacodynamics
  40. [40]

    Li W, Wan L, He S. “Cost-effectiveness of first-line immune checkpoint inhibitor therapies, alone or combined with targeted agents, for unresectable hepatocellular carcinoma in China: an economic evaluation using network meta-analysis.” Immunotherapy (2026). PMID: 41860583 ↗

    L1SR_OBSCited in: Pharmacodynamics
  41. [41]

    Bo W, Wang Z, Dong X et al.. “Systematic review of the efficacy and safety of lenvatinib vs. sorafenib as first-line treatments for hepatocellular carcinoma.” Clinics (Sao Paulo, Brazil) (2026). PMID: 41720053 ↗

    L1SR_OBSCited in: Pharmacodynamics
  42. [42]

    Remitha NPSI, Sasmana IGAP, Kusuma IKWA et al.. “A Network Meta-Analysis Comparing the Efficacy of Lenvatinib, Atezolizumab plus Bevacizumab, and Sorafenib in the Treatment of Unresectable Hepatocellular Carcinoma.” Asian Pacific journal of cancer prevention : APJCP (2026). PMID: 41945955 ↗

    L1SR_OBSCited in: Pharmacodynamics
  43. [43]

    Payo-Serafín T, Méndez-Blanco C, Fernández-Palanca P et al.. “Risk versus Benefit of Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Clinical pharmacology and therapeutics (2024). PMID: 38803056 ↗

    L1SR_MA_RCTCited in: Indications and Clinical Use
  44. [44]

    Dercle L, Geyer S, Nixon AB et al.. “Radiomic signatures to estimate survival in patients with advanced hepatocellular carcinoma treated with sorafenib: Cancer and Leukemia Group B 80802 (Alliance).” ESMO open (2025). PMID: 41337859 ↗

    L1RCTCited in: Indications and Clinical Use
  45. [45]

    Qin S, Gu S, Chan SL et al.. “Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study.” The Lancet. Oncology (2025). PMID: 41308676 ↗

    L1RCTCited in: Indications and Clinical Use, Adverse Effects and Toxicity
  46. [46]

    Hattenhauer T, Mispelbaum R, Heine A et al.. “On-treatment modified Glasgow Prognostic Score (mGPS) in hepatocellular carcinoma treated with atezolizumab and bevacizumab provides prognostic information.” Frontiers in immunology (2025). PMID: 41142780 ↗

    L1RCTCited in: Indications and Clinical Use, Adverse Effects and Toxicity
  47. [47]

    Neoh CF, Yong MK, Rowley L et al.. “Antifungal prophylaxis in patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia receiving sorafenib during initial induction and consolidation treatment in ALLG AMLM16 trial.” The Journal of antimicrobial chemotherapy (2025). PMID: 41133432 ↗

    L1RCTCited in: Indications and Clinical Use, Adverse Effects and Toxicity
  48. [48]

    Xu XQ, Li WM, Shi LC et al.. “Impact of temporary atezolizumab and bevacizumab interruption on survival in advanced HCC: an IMbrave150 analysis.” The oncologist (2025). PMID: 40891895 ↗

    L1RCTCited in: Indications and Clinical Use
  49. [49]

    Chen QF, Jiang X, Hu Y et al.. “Interventional arterial chemotherapy versus sorafenib for advanced hepatocellular carcinoma in China: a health economic evaluation of open-label, randomised, phase 3 study.” BMJ open (2025). PMID: 40436447 ↗

    L1RCTCited in: Indications and Clinical Use
  50. [50]

    Lau G, Sangro B, Cheng AL et al.. “Immune-mediated adverse events and overall survival with tremelimumab plus durvalumab and durvalumab monotherapy in unresectable HCC: HIMALAYA phase III randomized clinical trial.” Hepatology (Baltimore, Md.) (2026). PMID: 40384092 ↗

    L1RCTCited in: Indications and Clinical Use
  51. [51]

    Zhou J, Bai L, Luo J et al.. “Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): a randomised, controlled, phase 3 trial.” The Lancet. Oncology (2025). PMID: 40349716 ↗

    L1RCTCited in: Indications and Clinical Use
  52. [52]

    Yau T, Galle PR, Decaens T et al.. “Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial.” Lancet (London, England) (2025). PMID: 40349714 ↗

    L1RCTCited in: Indications and Clinical Use
  53. [53]

    Haruna Y, Yakushijin T, Yamakawa M et al.. “Anticancer effects of vitamin K combined with transarterial chemoembolization in hepatocellular carcinoma, a randomized controlled trial.” British journal of cancer (2025). PMID: 40263401 ↗

    L1RCTCited in: Indications and Clinical Use
  54. [54]

    Rimassa L, Chan SL, Sangro B et al.. “Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC.” Journal of hepatology (2025). PMID: 40222621 ↗

    L1RCTCited in: Indications and Clinical Use
  55. [55]

    Gao Y, Cheng AL, Li LX et al.. “Evaluation of hyperprogressive disease with atezolizumab plus bevacizumab for hepatocellular carcinoma: A secondary analysis of the IMbrave150 trial.” International journal of cancer (2025). PMID: 40079683 ↗

    L1RCTCited in: Indications and Clinical Use
  56. [56]

    Zugman M, McDermott DF, Escudier BJ et al.. “Updated overall survival in patients with prior checkpoint inhibitor therapy in the phase III TIVO-3 study.” The oncologist (2025). PMID: 39912344 ↗

    L1RCTCited in: Indications and Clinical Use
  57. [57]

    Lim HY, Heo J, Peguero JA et al.. “Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC.” Hepatology (Baltimore, Md.) (2025). PMID: 39141577 ↗

    L4TRIAL_NONRANDOMCited in: Dose and Administration, Dose Modification
  58. [58]

    Li TZ, Huang FD, Yan JX et al.. “Discovery of dimeric guaianolides with all carbon linkers as potential antihepatoma agents.” European journal of medicinal chemistry (2025). PMID: 40972424 ↗

    L5OTHERCited in: Dose and Administration, Dose Modification
  59. [59]

    Wang R, Yao SX, Pang YW et al.. “Design, synthesis and biological evaluation of novel platelet-derived growth factor receptor-α (PDGFR-α) inhibitors based on 4-anilinoquinoline and 4-anilinoquinazoline scaffolds.” European journal of medicinal chemistry (2025). PMID: 40749254 ↗

    L5OTHERCited in: Dose and Administration, Dose Modification
  60. [60]

    Ay EN, Çakır F, Akyüz S et al.. “Synthesis, characterization, In vitro and In silico investigations of novel 1,2,3-triazole substituted salicylic acid phenolic hydrazones hybrids targeting TGF-β2 expression in colorectal carcinoma.” European journal of medicinal chemistry (2025). PMID: 40582189 ↗

    L5OTHERCited in: Dose and Administration, Dose Modification
  61. [61]

    Siddique A, Shaheen S, Iftikhar A et al.. “Bicyclic 2-aminopyrimidine derivatives as potent VEGFR-2 inhibitors and apoptosis Inducers: Structure-Guided design, synthesis, anticancer assessment, and in-silico exploration.” European journal of medicinal chemistry (2025). PMID: 40378718 ↗

    L5OTHERCited in: Dose and Administration, Dose Modification
  62. [62]

    Ewieda SY, Sonousi A, Kamal AM et al.. “Design, synthesis, and cytotoxicity screening of novel pyrazolopyrimidines over renal cell carcinoma (UO-31 cells) as p38α inhibitors, and apoptotic cells inducing activities.” European journal of medicinal chemistry (2025). PMID: 39527892 ↗

    L5OTHERCited in: Dose and Administration, Dose Modification
  63. [63]

    Moradi M, Mousavi A, Řezníčková E et al.. “Identification of furo[2,3-d]pyrimidin-4-ylsulfanyl-1,3,4-thiadiazole derivatives as novel FLT3-ITD inhibitors.” European journal of medicinal chemistry (2024). PMID: 39427515 ↗

    L5OTHERCited in: Dose and Administration
  64. [64]

    Do Cao C, Godbert Y, Bardet S et al.. “ENDOCAN TUTHYREF network consensus recommendations: Refractory follicular-derived thyroid cancer.” Annales d'endocrinologie (2025). PMID: 40345488 ↗

    L1GUIDELINECited in: Dose Modification
  65. [65]

    Luo J, Li Z, Ge J et al.. “Exploring the optimal regimen in advanced hepatocellular carcinoma: a protocol of individual patient data network meta-analysis of randomized controlled trials.” Frontiers in immunology (2026). PMID: 41988192 ↗

    L5SR_MA_RCTCited in: Adverse Effects and Toxicity
  66. [66]

    Lin Y, Liao Y, Luo B et al.. “First-line immune checkpoint inhibitors plus targeted therapy versus sorafenib or lenvatinib monotherapy for unresectable or advanced hepatocellular carcinoma: a meta-analysis of phase 3 trials.” Frontiers in immunology (2025). PMID: 41169385 ↗

    L1SR_OBSCited in: Adverse Effects and Toxicity
  67. [67]

    Sanduzzi-Zamparelli M, Matilla A, Lledo JL et al.. “Clinical Trial: Early Nivolumab Addition to Regorafenib in Patients With Hepatocellular Carcinoma in Second-Line (The GOING Trial).” Alimentary pharmacology & therapeutics (2026). PMID: 41725391 ↗

    L4TRIAL_NONRANDOMCited in: Adverse Effects and Toxicity
  68. [68]

    Singh K, Rastogi S, Singh A et al.. “Clinico-radiological outcomes after discontinuation of sorafenib in non-abdominal desmoid-type fibromatosis: Final results from a phase-II SORASTOP study from India.” European journal of cancer (Oxford, England : 1990) (2026). PMID: 41610807 ↗

    L4TRIAL_NONRANDOMCited in: Adverse Effects and Toxicity
  69. [69]

    Berthod G, Cisarovsky C, Petrova T et al.. “Sorafenib plus selective internal radiotherapy with 90Y resin microspheres for the treatment of uveal melanoma with liver metastasis: a phase I trial.” British journal of cancer (2026). PMID: 41381843 ↗

    L4TRIAL_NONRANDOMCited in: Adverse Effects and Toxicity
  70. [70]

    Bi F, Qin S, Gu S et al.. “Analysis of common treatment-related adverse events of donafenib and its correlation with efficacy: exploratory analysis of the ZGDH3 study.” European journal of medical research (2025). PMID: 41163129 ↗

    L2RCTCited in: Adverse Effects and Toxicity
  71. [71]

    Ying T, E S, Ying H. “Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis.” Annals of medicine (2026). PMID: 41725538 ↗

    L1SR_OBSCited in: Adverse Effects and Toxicity
  72. [72]

    Crown O, Odubanjo OV, Adeyinka OS et al.. “Cathepsin Inhibitor Suppresses the Growth of Ectopic Hepatocellular Carcinoma Tumors in Mouse Models.” ACS pharmacology & translational science (2026). PMID: 41988376 ↗

    L5OTHERCited in: Adverse Effects and Toxicity
  73. [73]

    Lin KH, Lin YJ, Hong YB et al.. “Glutamic Acid-Chelated Cobalt Stabilizes G-Quadruplexes and Selectively Suppresses Hepatocellular Carcinoma Growth.” Oncology research (2026). PMID: 41930173 ↗

    L5OTHERCited in: Adverse Effects and Toxicity
  74. [74]

    Solana-Altabella A, Megías-Vericat JE, Ballesta-López O et al.. “Drug-drug interactions associated with FLT3 inhibitors for acute myeloblastic leukemia: current landscape.” Expert review of clinical pharmacology (2023). PMID: 36708283 ↗

    L5REVIEW_NARRATIVECited in: Drug Interactions
  75. [75]

    Sharma R, Motedayen Aval L. “Beyond First-Line Immune Checkpoint Inhibitor Therapy in Patients With Hepatocellular Carcinoma.” Frontiers in immunology (2021). PMID: 33790915 ↗

    L5REVIEW_NARRATIVECited in: Drug Interactions
  76. [76]

    Tsang J, Wong JSL, Kwok GGW et al.. “Nivolumab + Ipilimumab for patients with hepatocellular carcinoma previously treated with Sorafenib.” Expert review of gastroenterology & hepatology (2021). PMID: 33666530 ↗

    L5REVIEW_NARRATIVECited in: Drug Interactions
  77. [77]

    Benedicto A, Sanz E, Márquez J. “Ocoxin as a complement to first line treatments in cancer.” International journal of medical sciences (2021). PMID: 33437220 ↗

    L5REVIEW_NARRATIVECited in: Drug Interactions
  78. [78]

    Jung AR, Kim GE, Kim MY et al.. “Novel Therapeutic Strategy for Renal Cell Carcinoma: Niclosamide Enhances Sunitinib Efficacy via DNA Repair and Cell Cycle Pathways.” International journal of molecular sciences (2025). PMID: 41303409 ↗

    L5OTHERCited in: Drug Interactions
  79. [79]

    Liu X, Estaras M, Cosialls E et al.. “Synergistic antitumor activity of sorafenib and the NUPR1 inhibitor LZX-2-73 in multiple cancer models.” Cell death & disease (2025). PMID: 41249113 ↗

    L5OTHERCited in: Drug Interactions
  80. [80]

    Bandini A, Biso L, Viaggi C et al.. “Synergistic combination of the adrenergic antagonist SR59230A with common chemotherapeutic drugs and target therapies in cancer and endothelial cells.” Investigational new drugs (2025). PMID: 41108330 ↗

    L5OTHERCited in: Drug Interactions
  81. [81]

    Griffiths CD, Zhang B, Tywonek K et al.. “Toxicity Profiles of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.” JAMA network open (2022). PMID: 35849393 ↗

    L1SR_OBSCited in: Special Populations and Contraindications
  82. [82]

    Rubnitz JE, Lacayo NJ, Inaba H et al.. “Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2019). PMID: 31246522 ↗

    L1RCTCited in: Special Populations and Contraindications
  83. [83]

    Alonso JC, Casans I, González FM et al.. “Economic evaluations of radioembolization with Itrium-90 microspheres in hepatocellular carcinoma: a systematic review.” BMC gastroenterology (2022). PMID: 35780112 ↗

    L2SR_OBSCited in: Special Populations and Contraindications
  84. [84]

    Mcculloch M, Russin M, Nachat A. “Recurrence of Epithelioid Hemangioendothelioma during Pregnancy: Case Report and Systematic Review.” The Permanente journal (2016). PMID: 27479949 ↗

    L4SR_OBSCited in: Special Populations and Contraindications
  85. [85]

    Meany HJ, Widemann BC, Hinds PS et al.. “Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors.” Pediatric blood & cancer (2021). PMID: 34383370 ↗

    L4TRIAL_NONRANDOMCited in: Special Populations and Contraindications
  86. [86]

    Federico SM, Caldwell KJ, McCarville MB et al.. “Phase I expansion cohort to evaluate the combination of bevacizumab, sorafenib and low-dose cyclophosphamide in children and young adults with refractory or recurrent solid tumours.” European journal of cancer (Oxford, England : 1990) (2020). PMID: 32325418 ↗

    L4TRIAL_NONRANDOMCited in: Special Populations and Contraindications
  87. [87]

    Reed DR, Mascarenhas L, Manning K et al.. “Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies.” Cancer medicine (2016). PMID: 26714427 ↗

    L4TRIAL_NONRANDOMCited in: Special Populations and Contraindications
  88. [88]

    Kim A, Widemann BC, Krailo M et al.. “Phase 2 trial of sorafenib in children and young adults with refractory solid tumors: A report from the Children's Oncology Group.” Pediatric blood & cancer (2015). PMID: 26207356 ↗

    L4TRIAL_NONRANDOMCited in: Special Populations and Contraindications

Revision History

All updates applied to this page

Loading revisions…