Nursing Pharmacology:  Chemotherapy: Adverse Effects

 

• Pyrimidine-analog antimetabolites:

  • Fluorouracil (5-FU)

    • Schedule-dependent toxicity

    • Bolus infusion: mainly bone marrow suppression

    • Continuous infusion: GI toxicity

    • Myocardial ischemic syndrome (uncommon)

    • Reversible neurological effects:

      • Headaches

      • Ataxia

      • Somnolence

    • Dermatologic (common):

      • Dermatitis

      • Skin atrophy

      • Hyperpigmentation

  •  Cytarabine (ARA-C)

    • Continuous infusion: significant myelosuppression

    • GI toxicity (including oral mucositis)

    • High-dose protocols: cholestatic jaundice; cerebral/cerebellar toxicity

    • Neurotoxicity (increased risk with age > 40; diminished renal function

    • Conjunctivitis: (preventable by ophthalmic corticosteroids)

  • Gemcitabine  (Gemzar):

    • Myelosuppression (dose limiting)

    • Lethargy; malaise

• Purine Analog antimetabolites:

  • Fludarabine (Fludara)

    • Reversible, usually mild, neurotoxicity

    • Myelosuppression

    • Immunosuppression (opportunistic infection in some patients)

  •  Cladribine (Leustatin)

    • Myelosuppression

    • Immunosuppression

    • GI toxicity (mild)

  •  Pentostatin (Nipent)

    • Immunosuppression

    • Myelosuppression

    • Renal dysfunction

    • CNS toxicity; lever toxicity

  • 6-mercaptopurine (6MP)

    • Patients receiving allopurinol -- 75% reduction mercaptopurine does (elimination depends on xanthine oxidase activity, which is inhibited by allopurinol)

    • Cholestatic jaundice

    • Myelosuppression

    • Mild gastrointestinal effects

  • 6-thioguanine (6-TG):

    • Cholestatic jaundice (more common with 6-mercaptopurine

    • Myelosuppression

    • Gastrointestinal toxicity (mild)

  Other Antimetabolites:

  • Methotrexate:

    • Severe gastrointestinal toxicity}avoided by administration of leucovorin

    • Significant bone marrow hypoplasia}avoided by administration of leucovorin

    • Methotrexate may cumulative in fluid spaces (pleural effusions or ascites) -- may lead to severe toxicities as the drug elimination is prolonged.

    • Very high-dose methotrexate:

      • Acute renal injury (may be prevented by hydration and urine alkalinization)

      • Normal renal function is required for methotrexate elimination.

    • Lver toxicity

    • Idiosyncratic pneumonitis

  • Hydroxyurea (Hydrea):

    • Leukopenia (reversible upon discontinuation of drug)

    • Mild GI toxicity

    • Mild dermatologic changes with prolonged therapy

  Plant Alkaloids:

  • Vincristine (Oncovin):

    • Neurotoxicity can be dose limiting

      • Peripheral sensory neuropathy and/or autonomic neuropathy

      • Non-myelosuppressive

  • Vinblastine (Velban):

    • Dose limiting bone marrow hypoplasia (also seen with vinorelbine)

    • Significant neurotoxicity less frequently observed with vinblastine or vinorelbine than with vincristine)

  • Paclitaxel (Taxol)/docetaxel (Taxotere)

    • Infusion hypersensitivity (infusion vehicle may contribute)-- preventable by glucocorticoids.

    • Paclitaxel:

      • Bradyarrhythmias (A-V blockade)

      • Chest pain (atypical)

    • Myelosuppression: dose limiting

    • Peripheral neuropathy is common

    • Alopecia-- common

  Topoisomerase inhibitors:

  • Etoposide (VP-16,VePe-sid)/teniposide (Vumon)

    • Leukopenia: dose limiting

    • IV administration:

      • Hypotension

      • Fever

      • Bronchus spasm

      • Anaphylaxis

  • Anthracyclines and related compounds (doxorubicin (Adriamycin), daunorubicin (DaunoXome), idarubicin (Idamycin)) 

    • Myelosuppression

    • GI toxicity

    • Severe vesicants (blistering, tissue necrosis at injection site)

    • Long-term administration: limited by cumulative dose-dependent myocardial toxicity

    • Irreversible cardiomyopathy: significant risk with cumulative doses > 500 milligrams/m^2

      • Conference cyclophosphamide administration or radiation therapy may lower acceptable cumulative dose.

    • dactinomycin (Cosmegen):

      • Limited clinical use

      • Myelosuppression

  • Anthracenedione (mitoxantrone (Novantrone))

    • Cardiotoxicity

    • Significant myelosuppression

• Alkylating agents:

  • Depression in spermatogenesis

  • Depression in oogenesis

  • Mutagenic

  • Carcinogenic

  • Secondary leukemias

    • Patients receiving alkylating agents for treatment of Hodgkin's or non-Hodgkin's lymphoma:

      • 2% incidence of secondary myeloid leukemia (further increased incidence by addition of radiation therapy)

      • Not all alkylating agents equally leukemogenic

        • Melphalan: higher incidence compared to cyclophosphamide (in treating ovarian carcinoma)

    • Most common dose limiting toxicity: myelosuppression

  • Cyclophosphamide (Cytoxan):

    • Hemorrhagic cystitis (acrolein metabolite)

      • Prevented by adequate hydration and through the use of the bladder protectant, mesna

    • Chronic bladder inflammation

    • Antidiuretic effect (action on distal tubule)

    • Immunosuppression (myelosuppressive)

    • Acute myocardial necrosis (rare)

  • Ifosfamide (Ifex):

    • More urotoxic then cyclophosphamide (Cytoxan) (commonly administered with mesna)

    • Less myelosuppressive than cyclophosphamide

    • Neurotoxicity: reversible change in mental status.

  • Melphalan (Alkeran):

    • Especially leukemogenic

    • Pulmonary fibrosis (rare)

  • Busulfan (Myleran)

    • Myeloid stem cell toxicity

    • Bone marrow hypoplasia

    • Interstitial pneumonitis (rare)

    • Progressive pulmonary fibrosis (rare)

  • Mechlorethamine (Mustargen):

    • Severe vesicant (blistering)

  • Chlorambucil (Leukeran)--structurally similar to mechlorethamine, generally well tolerated

  • Thiotepa -limited clinical use

  • Nitrosoureas (carmustine {BCNU}; lomustine {CCNU})

    • Delayed, cumulative myelosuppression

    • Increase in hepatic enzyme levels (moderate, reversible)

    • Prolonged treatment: progressive renal insufficiency

    • Leukemogenic

  • Platinum agents: Cisplatin (Platinol) and Carboplatin (Paraplatin) (not true alkylating agents, but do cause DNA cross-linking):

    •  Cisplatin (Platinol): Renal toxicity {toxic to proximal and distal renal tubule epithelial cells}

      • Adequate hydration and the use of high-ceiling diuretics (furosemide) or osmotic diuretics (mannitol) decrease likelihood of Nephrotoxicity

      • Nausea

      • Vomiting

      • Sensory neuropathy

      • High-frequency hearing loss -- not uncommon

      • Mild myelosuppression

    •   Carboplatin  (Paraplatin):  

      • Less nephrotoxic then cisplatin

      • Less ototoxic than cisplatin

      • Less nausea and vomiting than cisplatin

      • More myelosuppressive than cisplatin

• Antitumor antibiotics:

  • Bleomycin  (Blenoxane):

    • Pulmonary toxicity: chronic interstitial pneumonitis (most serious toxicity)

    • Test does required -- bleomycin infusion may cause hypersensitivity reactions

    • Little myelosuppressive effect

  • Mitomycin  (Mutamycin):

    • Delayed myelosuppression

    • May produce progressive renal failure-microangiopathic anemia (hemolytic-uremic syndrome)

• Other drugs:

  • Dacarbazine  (DTIC):

    • Some myelosuppression

    • Nausea/vomiting (may be severe)

  • Procarbazine  (Matulane):

    • Peripheral sensory neuropathy

    • Mood and mental status changes

    • Nausea/vomiting which may be severe

  • L- asparaginase  (El-spar):

    • Hypersensitivity reactions; anaphylaxis

    • Hepatotoxicity-- occasional

    • Hancreatitis-- occasional

    • Hhromboses-- occasional

       

Slapak, C.A., and Kufe, D.W. Principles of Cancer Therapy : In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 523-537.