Medical Pharmacology Chapter 33-34:  Anticancer Drugs

• Natural Products:  Vinca Alkaloids

  • Vinorelbine (Navelbine)

    • Absorption, Distribution, Biotransformation, Excretion:

      • Vinorelbine (Nevelbine, VRL) exhibits pharmacological properties similar to other vinca alkaloids.

        • Accordingly, after rapid IV administration, vinorelbine plasma levels decline first rapidly and then with a slow elimination phase exhibiting a terminal half-life in the range of 20-50 hours, overall a triphasic curve.⁸

        • Vinorelbine was the initial vinca alkaloid exhibiting oral activity, showing comparable pharmacokinetic properties to the IV administered agent.

          • This formulation is available in certain countries with drug oral bioavailability estimated about 40%.⁸

      • Vinorelbine is substantially bound, about 85%, to plasma proteins, mainly α1-acid glycoprotein, albumin and lipoproteins.

        • Vinorelbine also binds to platelets.

      • Except for the CNS (central nervous system) vinorelbine exhibits wide distribution, penetrating nearly all tissues.¹⁰ 

        • The underlying reason for why distribution is found in the lipophilic character of vinorelbine.

          • Vinorelbine lipophilicity (manifest as ready partitioning into and through cell membrane lipid bilayers) is noted among the highest of the vinca alkaloids.¹⁰

      • Vinorelbine is primarily (as much as 80%) excreted in the feces following hepatic metabolism. The primary cytochrome P450 isoform responsible for vinorelbine biotransformation is CYP3A.

        • Urinary excretion accounts for about 20% of drug disposition, mainly in the form of the parent compound.

        • Most metabolites do not exhibit antineoplastic activity; however, the deacetyl-VRL metabolite may exhibit comparable pharmacological activity as the parent compound.¹⁰

    • Clinical Uses:

      • Vinorelbine exhibits antineoplastic activity against both breast cancer and non-small cell lung cancer (SCLC).¹

         

        • Gefinitib versus Vinorelbine-cisplatin as Adjuvant  Treatment in Non-small Cell Lung Cancer¹¹

          Attribution: Kim E Gefinitib versus vinorelbine-cisplatin as adjuvant treatment in NSCLC. In stage II-IIIA NSCLC with EGFR-activating mutation https://www.youtube.com/watch?v=0MpwA2kY66k (6/2017) OBRoncology Youtube Channel:  https://www.youtube.com/channel/UCn_dOPbmzqeL7glzj1yM1ug

        • Since vinorelbine is metabolized (detoxified) mainly by the liver, a patient exhibiting hepatic dysfunction may require dosage alteration.

          • Dosage change does not appear required in cases of compromised kidney function. ⁸

    • Toxicities:

      • Vinca alkaloids toxicities have been described earlier.

        • Vinorelbine administration is associated with myelosuppression (similar to that seen with vinblastine and by contrast to the neurotoxicity as the prominent vincristine toxicity).⁸

          • The most prominent myelosuppressive toxicity associated with vinorelbine is granulocytopenia.¹ 

            • Limited thrombocytopenia may also be noted.¹

      • Vesicant Chemotherapy Agents⁹

        Alkylating agents	Antitumor antibiotics	Anthracyclines	Taxane	Vinca alkaloids	Non-classical alkylating agent
        Carmustine Dacarbazine Mcchlorethamine Streptozocin Treosulfan	Dactinomycin Mitomycin Mitoxantrone	Daunorubicin Doxorubicin Epirubicin Idarubicin	Paclitaxel	Vinblastine Vincristine Vindesine Vinorelbine	Amsacrine