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cisplatin (Platinol)

Indications: - metastatic testicular cancer - advanced bladder cancer - prostate cancer - osteosarcoma - Hodgkin's disease - non-Hodgkin's lymphoma - head & neck cancer - adrenal cortical carcinoma [6] - cervical cancer - endometrial cancer - breast cancer - ovarian cancer - lung cancer - esophageal cancer - gastric cancer - pancreatic adenocarcinoma - squamous cell carcinoma of the anus - neuroblastoma - bone marrow ablation prior to stem cell transplantation [6] Administration: 1) prehydration with 1-2 liters of fluid 8-12 hours prior to administration 2) monitor for anaphylactoid reaction Powder for injection: 10 mg, 50 mg Aqueous vials: 50 mg, 100 mg Needles, syringes, catheters etc for administration of cisplatin should NOT contain aluminum Monitor: creatinine, CBC, hearing, neurologic function Adverse effects: 1) common (> 10%) a) gastrointestinal - cisplatin is one of the most emetogenic agents used in cancer chemotherapy - nausea/vomiting - 76-100% of patients - may persist for 1 week - see chemotherapy induced nausea/vomiting for management b) nephrotoxicity 1] acute renal failure - dose-dependent - attenuated by hydration, & mannitol or furosemide - occurs in 30% of patients receiving 50-75 mg/m2 - associated with hypomagnesemia, hypokalemia, & hypocalcemia - early nephrotoxicity presents as polyuria without reduction in GFR - nephrogenic diabetes insipidus & reduction in GFR may occur 72-96 hours after cisplatin administration - proximal renal tubular acidosis (RTA-2) - Fanconi syndrome: aminoaciduria, glycosuria, uricosuria, phosphaturia, hypophosphatemia 2] chronic renal failure - occurs in patient receiving multiple courses - cisplatin accumulates in distal tubules c) chemotherapy-induced anemia - treat with packed red cells even if normal iron studies & with nephrotoxic chemotherapeutic agents [9] (evidence is weak) d) ototoxicity manifested as high-frequency hearing loss - sodium thiosulfate 6 hours after cisplatin chemotherapy may lower incidence of hearing loss in children [8] e) myelosuppression - onset 10 days - nadir 14-23 days - recovery 21-39 days 2) less common (1-10%) - anorexia, pain at site of injection 3) uncommon (< 1%) - optic neuritis, blurred vision, mouth sores, SIADH, bradycardia, arrhythmias, phlebitis, mild alopecia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, abnormal liver function tests, papilledema* 4) others [1,2,4] - peripheral neuropathy - dose & duration-dependent - axonal degeneration with damage to sensory nerves - neuritis - mild alopecia - hyperuricemia - hypomagnesemia resulting in hypokalemia - hypertension - Raynaud's phenomenon - hypercholesterolemia - secondary malignancies - acute myeloid leukemia (AML) - melanoma - heart failure [4] Poisoning: antidote is sodium thiosulfate Drug interactions: 1) aminoglycosides a) do not use within 3 days of cisplatin administration b) increases nephrotoxicity & ototoxicity of cisplatin 2) vancomycin a) do not use within 3 days of cisplatin administration b) increases nephrotoxicity & ototoxicity of cisplatin 2) amphotericin B 3) loop diuretics increase ototoxicity of cisplatin 4) phenytoin 5) fatty acid 16:4(n-3) in fish oil associated with resistance to cisplatin [7] Mechanism of action: - platinum complexes bind to & crosslink of DNA, which triggers apoptosis

Interactions

drug adverse effects of platinum-based chemotherapy

Related

platinum [Pt]

General

antineoplastic platinum complex; platinum-based chemotherapy

Properties

MISC-INFO: elimination route KIDNEY pregnancy-category D

References

  1. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 598
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
  5. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
  6. Deprecated Reference
  7. Daenen LGM et al Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid 16:4(n-3) After Consumption of Fish and Fish Oil. JAMA Oncol. Published online April 02, 2015. PMID: 26181186 http://oncology.jamanetwork.com/article.aspx?articleid=2212208
  8. Brock PR, Maibach R, Childs M et al Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med 2018; 378:2376-2385. June 21, 2018 PMID: 29924955 https://www.nejm.org/doi/full/10.1056/NEJMoa1801109
  9. NEJM Knowledge+ - Gilreath JA, Rodgers GM. How I treat cancer-associated anemia. Blood. 2020 Aug 13;136(7):801-813. PMID: 32556170 Free article. Review.

Databases & Figures

PUBCHEM correlations Therapeutic Inducers of Apoptosis