Flashcards in 08a Major Organ Toxicities (Antimetabolites/Alkylators) Lee Deck (60):
What are the common toxicities associated with Anti-Metabolites?
Myelosuppression, mucositis, alopecia, N/V, tumor lysis syndrome (TLS)
What needs to be added to MTX IV treatment when using Intermediate or High-dose?
What are some major toxicities associated with MTX?
Stomatitis/Mucositis. Myelosuppression (dose limiting). Neurologic. Renal
What are the Purine Analogues used?
Mercaptopurine (6-MP, Purinethol). Thioguanine (6-TG, Tabloid)
What are the toxicities associated with Purine Analogues (Mercaptopurine, Thioguanine)?
Cholestatic Liver Dysfunction! Myelosuppression, Mild N/V/D, stomatitis
What is the issue with What are the toxicities associated with Purine Analogues (Mercaptopurine, Thioguanine) and Allopurinol?
6-MP metabolized by Xanthine Oxidase, which is inhibited by Allopurinol. Azathioprine, an immunosuppressant, a prodrug to 6-MP. Thus, REDUCE dose of Azathioprine and 6-MP by 75%
What are the Pyrimidine Analogues used?
Fluorouracil (5-FU); Capecitabine (Xeloda; oral 5-FU); Cytarabine; Gemcitabine
What are the toxicities like for the Pyrimidine Analogues (Fluorouracil; Capecitabine)?
Depends on route, dose, and schedule. Bolus: Myelosuppression. Continuous infusion: Mucositis, diarrhea, hand/foot syndrome
What is Grade 1 Hand/Foot Syndrome?
Numbness, dysesthesia or paresthesia, tingling, painless swelling or erythema, and/or discomfort of hands or feet not disrupting normal activities
What is Grade 2 Hand/Foot Syndrome?
Painful erythema and swelling of hands or feet and/or discomfort affecting ADLs
What is Grade 3 Hand/Foot Syndrome?
Moist desquamation, ulceration, blistering or severe pain of hands or fee, or severe discomfort preventing work or performance of ADLs
What is Hand/Foot Syndrome also known as?
Palmar-Plantar Erythrodyesthesia (PPE)
What are the toxicities associated with Pyrimidine Analogue Cytarabine (Ara-C)?
Toxicities with high-dose: Conjuntivitis, Cerebellar dysfunction (coordination/balance)
What are the toxicities associated with Pyrimidine Analogue Gemcitabine (Gemzar)?
Myelosuppression. Mild N/V, stomatitis, increased LFTs
What are some toxicities with Efudex, Carax 0.5% cream (topical 5-FU)?
Application-site reaction, erythema, dryness, burning, pain, ulceration, allergic contact dermatitis. Cases of miscarriage/birth defect when applied to mucous membranes
What are the common toxicities associated with Alkylators?
Sterility/infertility/teratogenicity. Second malignancies
Which Alkylators unique toxicity is Nephrotoxicity?
What are the Platinum Alkylators used?
Cisplatin (Platinol); Carboplatin (Paraplatin); Oxaliplatin (Eloxatin)
What are the toxicities associated with Platinum Alkylators?
Severe N/V (acute and delayed) w/ Cisplatin. Hypersensitivity with repeated use. Ototoxicity. Neurotoxicity (peripheral and loss of taste). Renal toxicity
What is Renal Toxicity like with the Platinum Alkylators?
Cisplatin (Dose limiting toxicity (DLT)) > Carboplatin > Oxaliplatin. Dose-related toxicity of distal convoluted tubule and collecting duct
What are the unique toxicities associated with Cyclophosphamide (Cytoxan, Neosar, oral and injectables)?
Highly emetogenic for doses > 1500 mg/m2. Hemorrhagic cystitis
What are the more common toxicities associated with Busulfan?
Severe Synusoidal Obstruction Syndrome (SOS) of liver. Seizures. Hyperpigmentation of the skin (Busulfan Tan). Endocardial fibrosis (Busulfan Lung) < 1%
What is some patient education for Alkylator: Procarbazine (Matulane)?
Ethanol causes Disulfiram-Like reactions. Safe handling. Alert dietitian, provide list of foods to avoid
What are the different complications of the GI Tract?
Xerostomia/Dry mouth (radiation). Stomatitis/Mucositis/Esophagitis (MTX, 5-FU, High-dose). N/V (Cisplatin and others). Diarrhea (5-FU, Irinotecan). Constipation (Vincristine)
How does Radiation (RT) to H/N cause Xerostomia?
Damage salivary glands. Loss of salivary buffering capacity, pH, IgA. Reversible w/in 6-12 months after end of treatment. Increase oral bacteria --> Infection
What can be used to reduce Xerostomia?
Amifostine (Ethyol) 200mg/m2 or 500mg IV prior to RT. Pilocarpine (Salagen) 5-10mg PO TID, cholinergic
What is Mucositis/Stomatitis?
Non-specific effect of chemotherapy and radiation on basal epithelium of mouth. Pain, may progress to ulceration; may extend esophagus, entire GI tract. Symptoms: Local pain, anorexia, N/D, thrush
What are the main causes of Mucositis/Stomatitis?
Antimetabolites (MTX, FU, Cytarabine), Anthracyclines, High-dose Chemotherapy, Allogenic BMT
How can Mucositis/Stomatitis be prevented?
Active rinses w/ mouthwashes. Sodium bicarbonate rinse, saline rinse, before eating and drinking. Cryotherapy (chew on ice before high dose melphalan - marginally effective). Paliformin
What is the treatment for Mucositis/Stomatitis?
Palliative = symptom control. Topical anesthetics. Kaolin, Benadryl, Antacids. Mouthwashes
What is the site of action of MTX?
Inhibits DHF Reductase
What is the site of action of Leucovorin?
Increases the depleted N5, N10 Methylene THF
What is the site of action of 5-FU?
Inhibits Thymidylate Synthetase, if given with Leucovorin it increases this inhibition
What are the different Leucovorin options?
Leucovorin IV/PO. Levoleucovorin Injection (Fusilev) - dose 1/2 of LV
What are the indications for Leucovorin?
Rescue after high-dose MTX. Reduces toxicity and counteracts effects of impaired elimination and inadvertent overdoses of MTX. In combo w/ 5-FU in palliative treatment of advanced metastatic colorectal cancer
At what point is Leucovorin usually given with MTX?
When MTX > 500mg. Severe BM suppression and mucositis unless rescured by Leucovorin
What is Calcium Leucovorin?
A reduced folate which can replenish the folate pool depleted by MTX. It allows DNA synthesis to begin again even in presence of MTX. Begin 24-36 hrs after initiation of MTX. Starting dose 10-15mg/m2 IV
When can Calcium Leucovorin be stopped?
When MTX < 5x 10-8M (0.05 um) at 72 hrs
When should precaution be used with Leucovorin?
If ascites or third space fluid collection --> Prolonged excretion and increased toxicity of MTX - may require Leucovorin dose increase as well as prolonged Leucovorin rescure
When should MTX levels be obtained?
24, 48, 72 hrs after MTX started
What should be done at 48 hrs if MTX level is less than 1x10^-6 M?
Continue Leucovorin 10-15mg/m2 Q6h x8 doses, IV
What should be done at 48 hrs if MTX level is greater than 1x10^-6 M?
Increase Leucovorin to 50-100mg/m2 Q6h x8 doses IV until it falls below 1x10^-6, then follow other schedule
How should MTX never be written?
QD!!! It is a weekly dose, not daily
What is some patient education for MTX?
Inform MD if any signs of: Neutropenia (fever, chills, sore throat, cough). Bleeding, bruising. Mouth sores, SOB. Liver toxicity.
How can nephrotoxicity from High-Dose MTX be prevented?
SCr < 1.5 or CrCl > 60. Intensive hydration. Alkalinization of urine to pH > 7 with Na Bicarbonate in IV fluids
Which DDI with MTX causes a decreased elimination of MTX?
Probenecid and PPIs
What is the MOA of Nephrotoxicity caused by Cisplatin?
Proximal tubular damage. Elevated BUN/SCr, chronic Mg wasting. SCr poorly coorelate w/ CrCl
How can nephrotoxicity caused by Cisplatin be prevented?
Vigorous hydration with saline + Mg, K. Ensure diuresis w/ furosemide. Use analogue: Carboplatin. Uroprotectant: Amifostine
What is Amifostine (Ethyol)?
Prodrug to free thiol that binds and detoxifies Cisplatin - "free radical scavenger". Used to prevent cumulative renal toxicity associated w/ repeated administration of Cisplatin. Reduction of moderate to severe Xerostomia (dry mouth) in radiation treatment for head and neck cancer
What are the side effects associated with Amifostine (Ethyol)?
What drugs cause Hemorrhagic Cystitis (bladder toxicity)?
Cyclophosphamide, Ifosfamide. Caused be metabolite, ACROLEIN
What is used for prevention of Hemorrhagic Cystitis caused by Cyclophosphamide, Ifosfamide?
Mesna (binds to acrolein preventing its contact w/ bladder wall and subsequent damage). Suprahydration, patient should drink ~3L fluid/d x sever days and frequent voiding
What are the ADRs with Mesna?
N/V (sulfur smell)
What can be used for treatment of Hemorrhagic Cystitis is severe bleeding?
Bladder irrigation w/ saline, cytoscopy w/ fulguration. Bladder instillation w/ aminocaproic acid, formalin, or hydrocortisone
What is the dosing of Mesna like for IFX bolus?
IFX bolus: Mesna = 20% of Ifosfamide dose given at 0, 4, 8hr after IFX
What is the dosing of Mesna like for IFX continuous infusion?
Mesna continuous infusion at 60-100% IFX dose, then extra 12-24 hrs after end of IFX (till acrolein level falls to non-toxic level in the bladder)
What are the signs/symptoms of Ifosfamide-induced Encephalopathy?
Decrease in arousability and disorientation leading to somnolence, drowsiness, lethargy, hallucination, encephalopathy, stupor, personality changes, paranoia, mutism, muscle twitching, incontinence, seizures, coma
What are the risk factors for Ifosfamide-Induced Encephalopathy?
High dose, bolus dose, low albumin. Avoid concurrent benzos (also cause CNS effects) - difficult to diagnos
What is used in the treatment of Ifosfamide-induced Encephalopathy?
Methylene blue; 50mg IV TID