Trial reportPloS one2016
Phase I/II Trial of Sorafenib in Combination with Vinorelbine as First-Line Chemotherapy for Metastatic Breast Cancer.
Trial report in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00764972 (A Phase IB/II Trial of Combination of Vinorelbine With Sorafenib), which is not on this map. Cited by 8 papers.
What it found
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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.
A Phase IB/II Trial of Combination of Vinorelbine With Sorafenib (BAY 43-9006) as First-Line Treatment in Patients With Metastatic Breast Cancer
Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Identifying mitigating strategies for endothelial cell dysfunction and hypertension in response to VEGF receptor inhibitors.Clinical science (London, England : 1979) · 2024Article
- Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories.Biomolecules · 2023Review
- Inhibition of Hepatic CYP2D6 by the Active N-Oxide Metabolite of Sorafenib.The AAPS journal · 2019Article
- Sorafenib-Induced Acute Pancreatitis: Case Report and Review of the Literature.Journal of gastrointestinal cancer · 2019Review
- Sorafenib N-Oxide Is an Inhibitor of Human Hepatic CYP3A4.The AAPS journal · 2019Article
- A Pharmacokinetic Interaction Study of Sorafenib and Iced Teas in Rats Using UPLC-MS/MS: An Illustration of Beverage-Drug Interaction.BioMed research international · 2019Article
- Targeting protein quality control pathways in breast cancer.BMC biology · 2017Review
- Hepatocellular Carcinoma: Etiology and Current and Future Drugs.Journal of clinical and experimental hepatologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPreclinical models have reported a synergistic interaction between sorafenib and vinorelbine. We investigated the toxicity, efficacy, and pharmacokinetics interaction of this combination as first-line treatment for patients with metastatic breast cancer.
methodsPatients were HER2-negative and treated with vinorelbine 30 mg/m2 IV days 1,8 every 21 plus daily oral sorafenib. In the phase I portion (3+3 design) patients received sorafenib 200 mg BID (cohort 1) or 400 mg BID (cohort 2). In the phase II expansion, 21 more evaluable patients were planned to receive the maximum tolerated dose (MTD). Pharmacokinetic analysis was performed in 6 patients: blood concentrations were compared for each drug in the presence or absence of the other drug.
resultsIn cohort 1, one patient experienced a dose-limiting toxicity (DLT) (grade 3 pancreatitis), requiring the expansion of this cohort to 6 patients, without further documented DLTs. In cohort 2, one patient of six experienced a grade 4 DLT (asymptomatic rise in amylase not requiring drug discontinuation), establishing this dose level as the MTD (sorafenib 400 mg BID). After expansion at the MTD, a total of 27 patients (median age 57) were treated for a median of 8 cycles. One grade 5 febrile neutropenia occurred. With repeated cycles, 52% of patients required at least 1 dose reduction of either drug. One patient experienced a sustained grade 3 fatigue resulting in treatment discontinuation. The response rate was 30%. Median PFS was 5.7 months (95% CI 4.4-7.6), and clinical benefit (absence of disease progression at 6 months) was 48%. PK analysis showed a significant interaction between the two drugs, resulting in a higher Cmax of vinorelbine in the presence of sorafenib.
conclusionThe combination of sorafenib and vinorelbine at full doses is feasible but not devoid of toxicity, likely also due to a significant PK interaction.
trial registrationClinicalTrials.gov NCT00764972.
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