Cisplatin (Cisplatinum)

Article Author:
Joann Gold
Article Editor:
Avais Raja
Updated:
9/22/2019 12:01:46 PM
PubMed Link:
Cisplatin (Cisplatinum)

Indications

Cisplatin is an antineoplastic agent. Cisplatin, while highly toxic, is one of the most heavily utilized chemotherapeutic agents for hematologic and solid tumor malignancies. It can be used as a single-agent or in combination therapy for induction and neoadjuvant therapy. 

Adult indications:

Cisplatin is FDA approved for the treatment of advanced ovarian cancer, testicular cancer, and bladder carcinoma.[1][2] However, cisplatin is frequently used in an off-label fashion when the benefits may outweigh the risks of adverse drug effects. 

Malignancies that predominate in women such as breast cancer, cervical and endometrial carcinoma, and gestational trophoblastic neoplasia sometimes receive treatment with cisplatin in combination with other medications such as taxane derivatives, 5-FU, and doxorubicin.[3][4][5] While hormone-sensitive and Her2neu, positive tumors may respond well to targeted therapy, cisplatin is also useful in the treatment of triple-negative breast cancer as a single agent neoadjuvant therapy.[3]

Gastrointestinal malignancies such as esophageal, gastric, and hepatobiliary cancer have also been treated off-label with this medication, in addition to radiation.[6][7][8] Lung cancer, both small cell and non-small cell, can be treated off-label with combination therapy of etoposide and cisplatin.[9][10]

Other off-label uses include treatment for metastatic, advanced, and refractory cancers; this includes the treatment of Hodgkin lymphoma, non-Hodgkin lymphoma, penile cancer, thymoma, head and neck cancers, osteosarcoma, multiple myeloma, and mesothelioma.[11][12][13]

Pediatric indications:

Cisplatin has few indications for treatment in children. When utilized, its indications are for historically aggressive tumors. It is sometimes used to treat germ cell tumors, hepatoblastoma, medulloblastoma, neuroblastoma, and osteosarcoma, but universal guidelines on dosing and duration are not available.[14][15][16][17][18][17]

Mechanism of Action

Cisplatin acts via non-cell cycle specific cytotoxicity, which is achieved through covalent binding of platinum to the purine bases guanine and adenine. This covalent binding leads to intra-strand and inter-strand crosslinks causing subsequent strand breaks. While DNA repair mechanisms are at play, cells often undergo apoptotic or non-apoptotic cell death due to remnant damaged DNA, RNA, and proteins.[19] Cisplatin chemotherapy is particularly effective at targeting rapidly dividing cells as appreciated in rapidly growing malignant tumors.[20] Theoretically, cisplatin may not be as useful for slow-growing tumors.

Administration

Cisplatin can be administered as an injectable agent both intravenously and as an intra-arterial agent.[21] Cisplatin can also be utilized as an intraperitoneal agent as seen in the treatment of carcinomatosis and primary peritoneal carcinoma, however, this use is not FDA approved and is referred to as “off-label” use.[22] Before administration, the patient must achieve adequate hydration. Adequate hydration and urinary output should be maintained for 24 hours after administration. Anti-emetic agents can be utilized prophylactically to prevent nausea and vomiting.[23]

Dosing runs from 20 mg/m^2 to 100 mg/m^2, in 21 to 28-day cycles, depending on the malignancy treated.

Adverse Effects

Extravasation - If extravasation is suspected, the infusion should stop immediately. Any obvious fluid collection should get aspirated, and the extremity elevated. The antidote, sodium thiosulfate, should be administered.[24]

Secondary malignancy - Leukemia is the most common secondary malignancy after treatment with cisplatin, and this typically occurs many years after completion of treatment.[25][26]

Tumor lysis syndrome can occur after treatment with many chemotherapeutic agents, which manifests as hyperuricemia, alteration in hemodynamics, hyperkalemia, and azotemia. Uric acid-reducing treatments may be necessary.[25][27]

Common side effects of cisplatin include[27]:

  • Mild nausea
  • Vomiting 
  • Diarrhea
  • Temporary hair loss
  • Loss in the ability to taste food
  • Hiccups
  • Dry mouth
  • Dark urine
  • Decreased sweating
  • Dry skin
  • Dehydration

Drug interactions

Caution is necessary when administering cisplatin with any of the following medications. Most drug interactions result in cumulative and dose-dependent hematologic, renal, and neurotoxic effects. Cisplatin should also not be used with immunosuppressive medications due to cumulative myelosuppression.[28][29] 

  • Alpha-lipoic acid
  • Aminoglycosides
  • Baricitinib
  • BCG
  • Chloramphenicol
  • Clozapine
  • Deferiprone
  • Denosumab
  • Dipyrone
  • Echinacea
  • Fosphenytoin
  • Leflunomide
  • Lenogristim
  • Lipefilgrastim
  • Natalizumab
  • Nivolumab
  • Ocrelizumab
  • Palifermin
  • Pidotimod
  • Pimecrolimus
  • Promazine
  • Roflumilast
  • Siponimod
  • Sipuleleucel-T
  • Tacrolimus
  • Taxane derivatives
  • Tertomotide
  • Topotecan
  • Trastuzumab
  • Vaccinations
  • Vinorelbine

Contraindications

There are few absolute contraindications for cisplatin use for the treatment of malignancies. Severe hypersensitivity to cisplatin would preclude its administration. Cisplatin has been shown to cross the placenta and may cause fetal harm.[30][31] Women of reproductive age should use reliable contraception during treatment and up to a year from the final treatment date. Cisplatin is also present in the breastmilk of lactating women on a cisplatin regimen.[32] Breastfeeding is not recommended during treatment.[32] If hypersensitivity occurs, the provider should discontinue cisplatin immediately.[33] Cisplatin is absolutely contraindicated in patients who have had severe hypersensitivity reactions, and rechallenge is not recommended.

Monitoring

A pregnancy test is necessary to determine pregnancy status in female patients before administration of cisplatin.[30]

Hematologic - The clinician should order a complete blood count (CBC) before initiation of treatment and before each subsequent treatment course.[25]

Renal function - Serum creatinine, blood urea nitrogen, creatinine clearance, and electrolytes (Na, K, Ca, Mg) requires an assessment before treatment administration.[34][35]

Hearing and vestibular - Audiometric testing should be ordered in pediatric patients to determine baseline and before each administration. After discontinuing therapy, audiometric testing should continue for several years.[25][35][36]

Infusion - The site of infusion should be assessed before, during, and after drug administration to assess for infection and extravasation. The patient should be monitored clinically for complications of administration.[24][37][38]

One also has to monitor the patient for neuropathy, ocular changes, and signs of systemic infection.

Toxicity

Gastrointestinal toxicity - Nausea and vomiting are dose-related side effects can be severe and lead to metabolic derangements; this can persist for up to 1 week after administration. The strong recommendation is for prophylactic treatment with antiemetic agents.[39][25]

Myelosuppression - The chief concern with myelosuppression secondary to cisplatin use is the morbidity and mortality associated with infection. Monitor CBC and frequently assess for signs of infection. High clinical suspicion is necessary for infection and warrants a full workup.[25] Hematologic toxicity may require total treatment interruption. Often it will require dose modification if treatment is to continue.[25]

Neurotoxicity - Cisplatin is a dose-dependent neurotoxin.[40] Dose-related neurotoxicity most commonly manifests as peripheral neuropathy. This neuropathy may progress after discontinuation and in some cases may be irreversible.[25][41] While dosage may require alteration in the face of neuropathy, high-grade peripheral neuropathy may require total treatment discontinuation. 

Nephrotoxicity - Severe renal toxicity, including acute renal failure, may occur with Cisplatin administration. These effects are cumulative and dose-related. Pretreatment hydration plays a significant role in preventing renal toxicity.[25][34][35] The dose of cisplatin may have to be adjusted based on renal function with close monitoring of the glomerular filtration rate (GFR).[33]

Ocular toxicity/retinopathy - This adverse effects can manifest in a variety of ways from loss of color discrimination to cortical blindness. Improvement usually occurs after discontinuation of cisplatin, and in some cases, total recovery may be possible.[25][42]

Ototoxicity - Monitoring for ototoxicity includes assessing the patient for ringing in the ears, high-frequency hearing loss, and decreased the ability to follow conversations. Deafness has been reported but is not a common effect of cisplatin use. Loss of hearing acuity can be detrimental to the development of language in pediatric populations.[25][35]

Gonadotoxicity - Cisplatin is toxic to the gonads; it can cause impairment of spermatogenesis and dose-dependent ovarian failure leading to premature menopause.[25]

Enhancing Healthcare Team Outcomes

Interprofessional collaboration and care coordination between physicians, nurses, pharmacists, and other related healthcare providers enhances team performance and patient outcomes.[43] Working as a team while caring for patients undergoing treatment with cisplatin is of great importance.[44] As a team, monitoring for side effects and toxicity can be more efficient with fewer poor outcomes and earlier intervention.[45][44] Communication among healthcare professionals is crucial. For example, any dose greater than 100 mg/m^2 for a single treatment course requires verification with the initial medication prescriber. The oncology specialty-trained pharmacist should also monitor for the extensive drug-drug interactions that can occur with cisplatin, and alert the ordering clinician promptly upon finding ant reason for concern.

Nurses need to be aware of the importance of hydration and monitoring the site of IV infusion for extravasation. Also, all clinicians should monitor the patient for signs of infection, renal impairment, and development of tumor lysis syndrome. Open communication between the interprofessional team is vital to prevent the adverse effects of this agent while optimizing its therapeutic effect. [Level V]


References

[1] Ozols RF,Bundy BN,Greer BE,Fowler JM,Clarke-Pearson D,Burger RA,Mannel RS,DeGeest K,Hartenbach EM,Baergen R, Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003 Sep 1;     [PubMed PMID: 12860964]
[2] Kondagunta GV,Bacik J,Donadio A,Bajorin D,Marion S,Sheinfeld J,Bosl GJ,Motzer RJ, Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005 Sep 20;     [PubMed PMID: 16170162]
[3] Silver DP,Richardson AL,Eklund AC,Wang ZC,Szallasi Z,Li Q,Juul N,Leong CO,Calogrias D,Buraimoh A,Fatima A,Gelman RS,Ryan PD,Tung NM,De Nicolo A,Ganesan S,Miron A,Colin C,Sgroi DC,Ellisen LW,Winer EP,Garber JE, Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010 Mar 1;     [PubMed PMID: 20100965]
[4] Whitney CW,Sause W,Bundy BN,Malfetano JH,Hannigan EV,Fowler WC Jr,Clarke-Pearson DL,Liao SY, Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 May;     [PubMed PMID: 10334517]
[5] Fleming GF,Brunetto VL,Cella D,Look KY,Reid GC,Munkarah AR,Kline R,Burger RA,Goodman A,Burks RT, Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 Jun 1;     [PubMed PMID: 15169803]
[6] Cunningham D,Starling N,Rao S,Iveson T,Nicolson M,Coxon F,Middleton G,Daniel F,Oates J,Norman AR, Capecitabine and oxaliplatin for advanced esophagogastric cancer. The New England journal of medicine. 2008 Jan 3;     [PubMed PMID: 18172173]
[7] Tepper J,Krasna MJ,Niedzwiecki D,Hollis D,Reed CE,Goldberg R,Kiel K,Willett C,Sugarbaker D,Mayer R, Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008 Mar 1;     [PubMed PMID: 18309943]
[8] Valle J,Wasan H,Palmer DH,Cunningham D,Anthoney A,Maraveyas A,Madhusudan S,Iveson T,Hughes S,Pereira SP,Roughton M,Bridgewater J, Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. The New England journal of medicine. 2010 Apr 8;     [PubMed PMID: 20375404]
[9] Wozniak AJ,Crowley JJ,Balcerzak SP,Weiss GR,Spiridonidis CH,Baker LH,Albain KS,Kelly K,Taylor SA,Gandara DR,Livingston RB, Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1998 Jul;     [PubMed PMID: 9667264]
[10] Turrisi AT 3rd,Kim K,Blum R,Sause WT,Livingston RB,Komaki R,Wagner H,Aisner S,Johnson DH, Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. The New England journal of medicine. 1999 Jan 28;     [PubMed PMID: 9920950]
[11] Fornasiero A,Daniele O,Ghiotto C,Piazza M,Fiore-Donati L,Calabró F,Rea F,Fiorentino MV, Chemotherapy for invasive thymoma. A 13-year experience. Cancer. 1991 Jul 1;     [PubMed PMID: 2049749]
[12] Velasquez WS,Cabanillas F,Salvador P,McLaughlin P,Fridrik M,Tucker S,Jagannath S,Hagemeister FB,Redman JR,Swan F, Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;     [PubMed PMID: 3334893]
[13] Velasquez WS,McLaughlin P,Tucker S,Hagemeister FB,Swan F,Rodriguez MA,Romaguera J,Rubenstein E,Cabanillas F, ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994 Jun;     [PubMed PMID: 8201379]
[14] Cushing B,Giller R,Cullen JW,Marina NM,Lauer SJ,Olson TA,Rogers PC,Colombani P,Rescorla F,Billmire DF,Vinocur CD,Hawkins EP,Davis MM,Perlman EJ,London WB,Castleberry RP, Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study--Pediatric Oncology Group 9049 and Children's Cancer Group 8882. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 Jul 1;     [PubMed PMID: 15226336]
[15] Douglass EC,Reynolds M,Finegold M,Cantor AB,Glicksman A, Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: a Pediatric Oncology Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1993 Jan;     [PubMed PMID: 8380296]
[16] Kim H,Kang HJ,Lee JW,Park JD,Park KD,Shin HY,Ahn HS, Irinotecan, vincristine, cisplatin, cyclophosphamide, and etoposide for refractory or relapsed medulloblastoma/PNET in pediatric patients. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 2013 Oct;     [PubMed PMID: 23748464]
[17] Kreissman SG,Seeger RC,Matthay KK,London WB,Sposto R,Grupp SA,Haas-Kogan DA,Laquaglia MP,Yu AL,Diller L,Buxton A,Park JR,Cohn SL,Maris JM,Reynolds CP,Villablanca JG, Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. The Lancet. Oncology. 2013 Sep;     [PubMed PMID: 23890779]
[18] Marina NM,Smeland S,Bielack SS,Bernstein M,Jovic G,Krailo MD,Hook JM,Arndt C,van den Berg H,Brennan B,Brichard B,Brown KLB,Butterfass-Bahloul T,Calaminus G,Daldrup-Link HE,Eriksson M,Gebhardt MC,Gelderblom H,Gerss J,Goldsby R,Goorin A,Gorlick R,Grier HE,Hale JP,Hall KS,Hardes J,Hawkins DS,Helmke K,Hogendoorn PCW,Isakoff MS,Janeway KA,Jürgens H,Kager L,Kühne T,Lau CC,Leavey PJ,Lessnick SL,Mascarenhas L,Meyers PA,Mottl H,Nathrath M,Papai Z,Randall RL,Reichardt P,Renard M,Safwat AA,Schwartz CL,Stevens MCG,Strauss SJ,Teot L,Werner M,Sydes MR,Whelan JS, Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. The Lancet. Oncology. 2016 Oct;     [PubMed PMID: 27569442]
[19] Riddell IA, Cisplatin and Oxaliplatin: Our Current Understanding of Their Actions. Metal ions in life sciences. 2018 Feb 5;     [PubMed PMID: 29394020]
[20] Aggarwal SK, A histochemical approach to the mechanism of action of cisplatin and its analogues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 1993 Jul;     [PubMed PMID: 8515048]
[21] O'Dwyer PJ,Stevenson JP,Johnson SW, Clinical pharmacokinetics and administration of established platinum drugs. Drugs. 2000;     [PubMed PMID: 10864227]
[22] Armstrong DK,Bundy B,Wenzel L,Huang HQ,Baergen R,Lele S,Copeland LJ,Walker JL,Burger RA, Intraperitoneal cisplatin and paclitaxel in ovarian cancer. The New England journal of medicine. 2006 Jan 5;     [PubMed PMID: 16394300]
[23] Roila F,Molassiotis A,Herrstedt J,Aapro M,Gralla RJ,Bruera E,Clark-Snow RA,Dupuis LL,Einhorn LH,Feyer P,Hesketh PJ,Jordan K,Olver I,Rapoport BL,Roscoe J,Ruhlmann CH,Walsh D,Warr D,van der Wetering M, 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Annals of oncology : official journal of the European Society for Medical Oncology. 2016 Sep;     [PubMed PMID: 27664248]
[24] Ener RA,Meglathery SB,Styler M, Extravasation of systemic hemato-oncological therapies. Annals of oncology : official journal of the European Society for Medical Oncology. 2004 Jun;     [PubMed PMID: 15151940]
[25] Barabas K,Milner R,Lurie D,Adin C, Cisplatin: a review of toxicities and therapeutic applications. Veterinary and comparative oncology. 2008 Mar;     [PubMed PMID: 19178659]
[26] Packer RJ,Zhou T,Holmes E,Vezina G,Gajjar A, Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children's Oncology Group trial A9961. Neuro-oncology. 2013 Jan;     [PubMed PMID: 23099653]
[27] Baeksgaard L,Sørensen JB, Acute tumor lysis syndrome in solid tumors--a case report and review of the literature. Cancer chemotherapy and pharmacology. 2003 Mar;     [PubMed PMID: 12655435]
[28] Balis FM, Pharmacokinetic drug interactions of commonly used anticancer drugs. Clinical pharmacokinetics. 1986 May-Jun;     [PubMed PMID: 2426030]
[29] Furue H, [Drug interactions with anticancer agents]. Gan to kagaku ryoho. Cancer     [PubMed PMID: 3907502]
[30] Zheng X,Zhu Y,Zhao Y,Feng S,Zheng C, Taxanes in combination with platinum derivatives for the treatment of ovarian cancer during pregnancy: A literature review
. International journal of clinical pharmacology and therapeutics. 2017 Sep;     [PubMed PMID: 28737125]
[31] Brewer M,Kueck A,Runowicz CD, Chemotherapy in pregnancy. Clinical obstetrics and gynecology. 2011 Dec;     [PubMed PMID: 22031250]
[32] Cisplatin 2006;     [PubMed PMID: 30000655]
[33] Otani IM,Wong J,Banerji A, Platinum Chemotherapy Hypersensitivity: Prevalence and Management. Immunology and allergy clinics of North America. 2017 Nov;     [PubMed PMID: 28965633]
[34] Crona DJ,Faso A,Nishijima TF,McGraw KA,Galsky MD,Milowsky MI, A Systematic Review of Strategies to Prevent Cisplatin-Induced Nephrotoxicity. The oncologist. 2017 May;     [PubMed PMID: 28438887]
[35] Karasawa T,Steyger PS, An integrated view of cisplatin-induced nephrotoxicity and ototoxicity. Toxicology letters. 2015 Sep 17;     [PubMed PMID: 26101797]
[36] Brock PR,Knight KR,Freyer DR,Campbell KC,Steyger PS,Blakley BW,Rassekh SR,Chang KW,Fligor BJ,Rajput K,Sullivan M,Neuwelt EA, Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012 Jul 1;     [PubMed PMID: 22547603]
[37] Li L,Wu M,Yang JX,Wan XR,Huang HF,Pan LY,Shen K,Lang JH,Xiang Y, [Clinical analysis of hypersensitivity reaction of platinum in ovarian cancer and cervical cancer patients]. Zhonghua fu chan ke za zhi. 2016 Nov 25;     [PubMed PMID: 27916065]
[38] Handa S,Kuroiwa R,Miyano M,Shimizu H,Kamei D,Takei H,Sonou H,Yamamoto H,Murayama J,Sato A,Kato Y, Assessment of Injection Site Reactions for Peripheral Intravenous Oxaliplatin Infusion and Potential Remedies. Gan to kagaku ryoho. Cancer     [PubMed PMID: 27539041]
[39] Paw Cho Sing E,Robinson PD,Flank J,Holdsworth M,Thackray J,Freedman J,Gibson P,Orsey AD,Patel P,Phillips R,Portwine C,Raybin JL,Cabral S,Sung L,Dupuis LL, Classification of the acute emetogenicity of chemotherapy in pediatric patients: A clinical practice guideline. Pediatric blood     [PubMed PMID: 30729654]
[40] Avan A,Postma TJ,Ceresa C,Avan A,Cavaletti G,Giovannetti E,Peters GJ, Platinum-induced neurotoxicity and preventive strategies: past, present, and future. The oncologist. 2015 Apr;     [PubMed PMID: 25765877]
[41] Albers JW,Chaudhry V,Cavaletti G,Donehower RC, Interventions for preventing neuropathy caused by cisplatin and related compounds. The Cochrane database of systematic reviews. 2014 Mar 31;     [PubMed PMID: 24687190]
[42] Li Y,Li Y,Li J,Pi G,Tan W, Paclitaxel- and/or cisplatin-induced ocular neurotoxicity: a case report and literature review. OncoTargets and therapy. 2014;     [PubMed PMID: 25114574]
[43] Foronda C,MacWilliams B,McArthur E, Interprofessional communication in healthcare: An integrative review. Nurse education in practice. 2016 Jul;     [PubMed PMID: 27428690]
[44] Yang LY,Manhas DS,Howard AF,Olson RA, Patient-reported outcome use in oncology: a systematic review of the impact on patient-clinician communication. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2018 Jan;     [PubMed PMID: 28849277]
[45] Abueg KD, Interprofessional Management of Toxicities Related to Cancer Precision Medicine. Seminars in oncology nursing. 2017 Nov;     [PubMed PMID: 28927762]