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.
Cisplatin is FDA approved for the treatment of advanced ovarian cancer, testicular cancer, and bladder carcinoma. However, clinicians frequently use cisplatin off-label 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. 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.
Gastrointestinal malignancies such as esophageal, gastric, and hepatobiliary cancer have also been treated off-label with this medication, in addition to radiation. Lung cancer, both small cell and non-small cell, can be treated off-label with combination therapy of etoposide and cisplatin.
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.
Cisplatin has few indications for treatment in children. When utilized, its indications are for historically aggressive tumors. It is sometimes useful in treating germ cell tumors, hepatoblastoma, medulloblastoma, neuroblastoma, and osteosarcoma, but universal guidelines on dosing and duration are not available.
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. Cisplatin chemotherapy is particularly effective at targeting rapidly dividing cells as appreciated in rapidly growing malignant tumors. Theoretically, cisplatin may not be as useful for slow-growing tumors.
Cisplatin can be administered as an injectable agent both intravenously and as an intra-arterial agent. 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 “off-label” use. Before administration, the patient must achieve adequate hydration and must maintain hydration and urinary output for 24 hours after administration. Anti-emetic agents can be utilized prophylactically to prevent nausea and vomiting.
Dosing runs from 20 mg/m^2 to 100 mg/m^2 in 21 to 28-day cycles, depending on the malignancy treated.
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.
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.
Common side effects of cisplatin include:
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 concurrently with immunosuppressive medications due to cumulative myelosuppression.
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. 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. Breastfeeding is not recommended during treatment. If hypersensitivity occurs, the provider should discontinue cisplatin immediately. Cisplatin is absolutely contraindicated in patients who have had severe hypersensitivity reactions, and rechallenge is not a recommendation.
A pregnancy test is necessary to determine pregnancy status in female patients before the administration of cisplatin.
Hematologic - The clinician should order a complete blood count (CBC) before initiation of treatment and before each subsequent treatment course.
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.
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.
One also has to monitor the patient for neuropathy, ocular changes, and signs of systemic infection.
Gastrointestinal toxicity - Nausea and vomiting are dose-related side effects that 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.
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. Hematologic toxicity may require total treatment interruption. Often it will require dose modification if treatment is to continue.
Neurotoxicity - Cisplatin is a dose-dependent neurotoxin. Dose-related neurotoxicity most commonly manifests as peripheral neuropathy. This neuropathy may progress after discontinuation and, in some cases, might be irreversible. 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. The dose of cisplatin may have to be adjusted based on renal function with close monitoring of the glomerular filtration rate (GFR).
Ocular toxicity/retinopathy - These 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.
Ototoxicity - Monitoring for ototoxicity includes assessing the patient for ringing in the ears, high-frequency hearing loss, and decreased 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.
Gonadotoxicity - Cisplatin is toxic to the gonads; it can cause impairment of spermatogenesis and dose-dependent ovarian failure leading to premature menopause.
Interprofessional collaboration and care coordination between physicians, nurses, pharmacists, and other related healthcare providers enhances team performance and patient outcomes. Working as a team while caring for patients undergoing treatment with cisplatin is of great importance. As a team, monitoring for side effects and toxicity can be more efficient with fewer poor outcomes and earlier intervention. 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]
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