1. DH206: Pharmacology CH 23: Antineoplastic Drugs Lisa Mayo, RDH, BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. Antineoplastic Drugs Outline  Antineoplastic Agents  Classification  Adverse Drug Effects  Dental Implications  Bisphosphates

3. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Antineoplastic Drugs  Designed to treat neoplasms that cannot be treated with surgery  Can be used in combo with surgery & radiation  Called “Cancer chemotherapeutic agents”  Most TOXIC drugs on market – interfere with cellular DNA (healthy & cancer cells)

4. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Antineoplastic Drugs  Some cancers resistant to chemo by: 1. De novo resistance: neoplams was ALWAYS resistant to drugs 2. Acquired resistance: Resistance occurs through mutation of neoplasms

5. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification

6. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification Antineoplastic agents divided into 2 categories 1. Cell-cycle-specific (CCS) antineoplastic agents Affect cells that are actively multiplying 2. Cell-cycle-nonspecific (CCNS) antineoplastic agents Kill cells that are actively multiplying or at rest More toxic than CCS CCS DRUGSACTION AntimetabolitesDNA synthesis inhibitors CCNS DRUGSACTION Alkylating AgentsDNA alkylating drugs Antitumor ABX Plant Alkaloids

7. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification CCS DRUGS ANTIMETABOLITIES Cladribine(Leustatin) Cytarabine(Cytosar-U) Floxuridine(FUDR) Fludarabine phosphate(Fludara) Fluorouracil Gemcitabine(Gemsar) Meracaptopurine(Purinethol) Methotrexate(Mexate) Pentostatin(Nipent) CCNS DRUGS: ALKYLATING AGENTS Altretamine(Hexalen) Busulfan(Myleran) Chloramubucil(Leukeran) Carboplatin(Paraplatin) Cisplatin(Plantinol) Cyclophosphamide(Cytoxan) Ifofamide(Ifex) Lomustine(CeeNU) Melphalan(Alkeran) Mitomycin(Mutamycin) Mechlorethamine HCl(Mustargen) Procarbazine HCl(Matulane) Streptozocin(Zanosar) Thiotepa(Thioplex)

8. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification CCNS DRUGS: ANTITUMOR ABX Bleomycin(Blenoxane) Danunorubicin HCl(Cerubidine) Doxorubicin HCl(Adriamycin) Idaribicin HCl(Idamycin) CCNS DRUGS: PLANT ALKALOIDS Mitotic InhibitorsVinblastine(Velban) Vincristine(Oncovin) Vinorelbine(Navelbine) TaxanesDocetaxel(Taxotere) Paclitaxel(Taxol) Topoisomerase Inhibitors Topotecan(Hycamtin) Etoposide(VePesid) Teniposide(Vumon) Irinotecan(Camptosar)

9. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification Other agents used in tx: DRUGCLASSUSES Flutamide(Eulexin) Leuprolide(Lupron) PrednisoneSystemic steroidLymphomas & Leukemia Tamoxifen(Novadex)AntiestrogenBreast cancer IMMUNOMODULATORS(CYTOKINES) Aldesleukin(Proleukin) Interferon alfa

10. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Classification  Oncologists “hit hard and fast” with drug therapy Many drugs have to stopped due to side effects (infection, decrease WBC) Cancer cells become resistant to drugs with time so “hit hard” with high doses  cetuximab(Erbitux) FDA approved in 2006 for tx squamous cell carcinoma head/neck + radiation

11. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Cisplatin and cyclosphamide are classified as what type of cancer chemotherapy drug? a. Alkylating agents b. Anthrecyclines c. Antimetabolites d. Vinca alkaloids

12. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Cisplatin and cyclosphamide are classified as what type of cancer chemotherapy drug? a. Alkylating agents b. Anthrecyclines c. Antimetabolites d. Vinca alkaloids

13. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Drug Effects

14. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Adverse Drug Effects  Table 23-2, p.259  Side effects due to non-selectivity of drugs ○ Faster growing cells affected the most (GI tract, bone marrow, hair follicles) ○ Early side effects are seen in these tissues  Most common ○ Nausea & vomiting ○ Bone marrow suppression = leads to leukopenia = ↑ risk for serious infections & thrombocytopenia ○ Hair loss, dry skin

15. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following is the most likely complication seen with chemotherapy treatment? a. Renal failure b. Alopecia c. Peripheral neuropathy d. Glaucoma

16. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Which of the following is the most likely complication seen with chemotherapy treatment? a. Renal failure b. Alopecia c. Peripheral neuropathy d. Glaucoma

17. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ All of the following are adverse effects of antineoplastic treatment EXCEPT which one? a. Mucositis of dorsum of tongue b. Gingival bleeding c. Xerostomia d. Stomatitis e. Thrush

18. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ All of the following are adverse effects of antineoplastic treatment EXCEPT which one? a. Mucositis of dorsum of tongue b. Gingival bleeding c. Xerostomia d. Stomatitis e. Thrush

19. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Dental Implications

20. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 40% patients on chemo drugs will have oral side effects DENTAL COMPLICATION NOTATION XerostomiaPreventive & Palliative Care CariesRoot caries Oral mucositisDifficult to maintain oral hygiene at home Occurs within 1wk starting chemo CHX should be recommended EsophagitisDamage to mucosal lining leads to dysphagia (swallowing difficulty) Oral candidiasisDue to leukopenia Bacterial infectionsPremed may be necessary due to leukopenia TasteAlterations: esp sweet & salty Bleeding & Impaired healing Result of thrombocytopenia & neutropenia

21. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Dental Implications

22. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Dental Implications  Avoid working on patients right AFTER they stop drug therapy Bone marrow depression still present, WBC count too low Refer to Box 23-3 & 23-4 on page 260 ORAL CARE BEFORE TX ORAL CARE DURING TX ORAL CARE AFTER TX Extract questionable teeth Med consultResume normal care OHIPremed may be needed Tx any infectionsTx depends on neutrophil count Monitor pt’s closely

23. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Bisphosphonates  1 st developed as drugs as alternative for HRT & osteoporosis 1996: aldendronate(Fosamax)  Action: ↓ actions of osteoclasts  Cancer patients: Excessive Ca is released in the blood & bone is resorbed IV bisphos’s used to tx  Osteoradionecrosis IV bisphos’s + dental extractions, surgery, endo, ortho, SCRP = Cause alterations to bone deposition & repair = osteoradionecrosis

24. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Bisphosphonates Clondronate(Bonefos) Pamidronate(Acredia) Zoledronate(Zometa) Ibandronate(Boniva) Risedronate(Actonel) Alendronate(Fosamax) Tiludronate(Skelid) Etidronate(Didronel) End in ~ronate

25. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ A patient is taking zolendronate(Zometa) for pain from multiple myeloma (a cancer.) Which of the following conditions can develop after periodontal debridement? a. Orthostatic hypotension b. Malignant hypertension c. Osteoradionecrosis of the jaw d. Multiple periodontal abscesses

26. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ A patient is taking zolendronate(Zometa) for pain from multiple myeloma (a cancer.) Which of the following conditions can develop after periodontal debridement? a. Orthostatic hypotension b. Malignant hypertension c. Osteoradionecrosis of the jaw d. Multiple periodontal abscesses

27. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Your patient with a history of breast cancer is undergoing chemotherapy with a drug called cisplatin(Platinol). All of the following are expected adverse effects of cisplastin EXCEPT which one? a. Nausea and vomiting b. Hair loss c. Xerostomia d. Brain hemorrhages e. Changes within the tissues of the oral cavity such as mucositis

28. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Your patient with a history of breast cancer is undergoing chemotherapy with a drug called cisplatin(Platinol). All of the following are expected adverse effects of cisplastin EXCEPT which one? a. Nausea and vomiting b. Hair loss c. Xerostomia d. Brain hemorrhages e. Changes within the tissues of the oral cavity such as mucositis