Trial reportBritish journal of cancer2012
Sorafenib in advanced melanoma: a critical role for pharmacokinetics?
Trial report in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02636426 (Sorafenib Administered Using a High-dose, Pulsatile Regimen in Patients With Advanced Solid Malignancies), which is not on this map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sorafenib Administered Using a High-dose, Pulsatile Regimen in Patients With Advanced Solid Malignancies: a Phase I Exposure Escalation Study
Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer.Endocrine-related cancer · 2015Trial
- A Phase II Study of Sorafenib Combined With Cetuximab in EGFR-Expressing, KRAS-Mutated Metastatic Colorectal Cancer.Clinical colorectal cancer · 2015Trial
- Insufficient ferroptosis in radiation-induced tumor cells promote Treg cell generation to induce radiotherapy resistance.Communications biology · 2026Article
- Inhibiting melanoma tumor growth: the role of oxidative stress-associatedFrontiers in immunology · 2025Article
- Pharmacokinetics and apparent Michaelis constant for metabolite conversion of sorafenib in healthy and hepatocellular carcinoma-bearing rats.Bioanalysis · 2024Article
- Arginase 2 negatively regulates sorafenib-induced cell death by mediating ferroptosis in melanoma.Acta biochimica et biophysica Sinica · 2022Article
- Relevance of Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in Routine Clinical Practice: A Pilot Study.Pharmaceutics · 2022Article
- Population Pharmacokinetic Modelling and Simulation to Determine the Optimal Dose of Nanoparticulated Sorafenib to the Reference Sorafenib.Pharmaceutics · 2021Article
- Nuances to precision dosing strategies of targeted cancer medicines.Pharmacology research & perspectives · 2020Review
- Sorafenib administered using a high-dose, pulsatile regimen in patients with advanced solid malignancies: a phase I exposure escalation study.Cancer chemotherapy and pharmacology · 2020Article
- Clinical development of targeted and immune based anti-cancer therapies.Journal of experimental & clinical cancer research : CR · 2019Review
- CLC-Pred: A freely available web-service for in silico prediction of human cell line cytotoxicity for drug-like compounds.PloS one · 2018Article
- Commentary on: "Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide".Clinical and translational science · 2017Article
- How 'Optimal' are Optimal Sampling Times for Tyrosine Kinase Inhibitors in Cancer? Practical Considerations.Clinical pharmacokinetics · 2016Review
- Alternative scheduling of pulsatile, high dose sunitinib efficiently suppresses tumor growth.Journal of experimental & clinical cancer research : CR · 2016Article
- The cutting edge of metastatic melanoma therapy.Melanoma management · 2016Review
- Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma.Cancer research · 2015Article
- Emerging targeted therapies for melanoma treatment (review).International journal of oncology · 2014Review
- A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2014Article
- Exposure-toxicity relationship of sorafenib in Japanese patients with renal cell carcinoma and hepatocellular carcinoma.Clinical pharmacokinetics · 2014Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInter-patient pharmacokinetic variability can lead to suboptimal drug exposure, and therefore might impact the efficacy of sorafenib. This study reports long-term pharmacokinetic monitoring of patients treated with sorafenib and a retrospective pharmacodynamic/pharmacokinetic analysis in melanoma patients. PATIENTS AND
methodsHeavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid). In the absence of limiting toxicity, dose escalation of 200 mg bid levels was done every 2 weeks. Plasma sorafenib measurement was performed at each visit, allowing a retrospective pharmacodynamic/pharmacokinetic analysis for safety and efficacy.
resultsIn all, 19 of 30 patients underwent dose escalation over 400 mg bid, and 28 were evaluable for response. The overall disease control rate was 61% (95% confidence interval (CI): 42.6-78.8), including three confirmed responses (12%). Disease control rate and progression-free survival (PFS) were improved in patients with high vs low exposure (80% vs 32%, P=0.02, and 5.25 vs 2.5 months, P=0.005, hazard ratio (HR)=0.28 (95% CI: 0.11-0.73)). In contrast, drug dosing had no effect on PFS. In multivariate analysis, drug exposure was the only factor associated with PFS (HR=0.36 (95% CI: 0.13-0.99)). Diarrhoea and anorexia were correlated with drug dosing, while hypertension and hand-foot skin reaction were correlated with drug exposure.
conclusionsAlthough sorafenib had modest efficacy in melanoma, these results suggest a correlation between exposure and efficacy of sorafenib. Therefore, dose optimisation in patients with low exposure at standard doses should be evaluated in validated indications.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.