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Sorafenib

Antineoplastic Agents
CATEGORIES

Antineoplastic Agents


ALIASES

Nexavar, Sorafenib


SUBSTANCES

sorafenib tosilate


ENVIRONMENTAL CONCERN: MODERATE
Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer). It has also received "Fast Track" designation by the FDA for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials. Sorafenib is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway.

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MODERATE
The T-value in the score for hazard refers to chronic toxicity. Underlying data for P, B and T comes from assessment report, see below. "The compound is considered as vP and vB."

Below is Hazard and Risk according to data from the assessment report for assessment report for Nexavar (sorafenib) 25 April 2014 EMA/CHMP/220738/2014


Hazard
Persistence: "There was no degradation after 28 days. DT50 (transformation in soil) - 187 days." Conclusion: vP.

Bioaccumulation: BCF = 7 250 "ratio fish/water concentration at the end of exposure." Conclusion: vB.

Chronic toxicity: There is NOEC /EC10 for 3 trophic levels, lowest NOEC /EC10 for fish 0,17 microg/L.

"The compound is considered as vP and vB."

Risk
The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = 0.0378 microg/L

PNEC = Lowest NOEC/EC10: 0.17 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.017 mikrog/L

PEC/PNEC = 2.224

Fass environmental information for Nexavar (sorafenib) (downloaded 2018-06-27)


Hazard
Persistence: "Sorafenib showed no degradation in a water-sediment system (OECD 308). Sorafenib is potentially persistent."

Bioaccumulation: "The BCFs was determined with 5300 for the higher concentration and >7300 for the lower concentration, where no steady-state was reached."

Chronic toxicity: here is NOEC /EC10 for 3 trophic levels, lowest NOEC /EC10 (EC10/28d; mortality) for fish 0.17 microg/L.

Risk
PEC/PNEC is based on sales data in Sweden in year 2015. PEC/PNEC = 0.2 which gives the environmental risk low. As stated above: "The compound is considered as vP and vB."

REFERENCES

  1. European Medicines Agency. European public assessment reports (EPAR).
  2. Fass.se för vårdpersonal