cisplatin (Platinol)
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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:
- prehydration with 1-2 liters of fluid 8-12 hours prior to administration
- monitor for anaphylactoid reaction
Powder for injection: 10 mg, 50 mg
Needles, syringes, catheters etc for administration of cisplatin should NOT contain aluminum
Monitor
creatinine, CBC, hearing, neurologic function
Adverse effects
- common (> 10%)
- 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
- nephrotoxicity
- 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
- chronic renal failure
- occurs in patient receiving multiple courses
- cisplatin accumulates in distal tubules
- acute renal failure
- chemotherapy-induced anemia
- treat with packed red cells even if normal iron studies & with nephrotoxic chemotherapeutic agents[9] (evidence is weak)
- ototoxicity manifested as high-frequency hearing loss
- sodium thiosulfate 6 hours after cisplatin chemotherapy may lower incidence of hearing loss in children[8]
- myelosuppression
- onset 10 days
- nadir 14-23 days
- recovery 21-39 days
- gastrointestinal
- less common (1-10%)
- anorexia, pain at site of injection
- uncommon (< 1%)
- optic neuritis, blurred vision, mouth sores, SIADH, bradycardia, arrhythmias, phlebitis, mild alopecia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, abnormal liver function tests, papilledema*
- 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
- heart failure[4]
- peripheral neuropathy
Poisoning: antidote is sodium thiosulfate
Drug interactions
- aminoglycosides
- do not use within 3 days of cisplatin administration
- increases nephrotoxicity & ototoxicity of cisplatin
- vancomycin
- do not use within 3 days of cisplatin administration
- increases nephrotoxicity & ototoxicity of cisplatin
- amphotericin B
- loop diuretics increase ototoxicity of cisplatin
- phenytoin
- 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
More general terms
Additional terms
References
- ↑ 1.0 1.1 Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 2.0 2.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 598
- ↑ 4.0 4.1 4.2 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
- ↑ 6.0 6.1 6.2 Deprecated Reference
- ↑ 7.0 7.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26181186 <Internet> http://oncology.jamanetwork.com/article.aspx?articleid=2212208
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29924955 https://www.nejm.org/doi/full/10.1056/NEJMoa1801109
- ↑ 9.0 9.1 NEJM Knowledge+
Gilreath JA, Rodgers GM. How I treat cancer-associated anemia. Blood. 2020 Aug 13;136(7):801-813. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32556170 Free article. Review.
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=441203
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=84691
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5311048
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2770
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2767