Tumor lysis syndrome treatment

Prior to initiation of treatment with chemotherapy, determine if tumor lysis syndrome precautions need to be implemented. 

The primary goals of management of tumor lysis syndrome are (1) prevention of renal failure and (2) prevention of electrolyte imbalances. Thus the best treatment for tumor lysis syndrome is prophylaxis to enable delivery of cytotoxic therapy for the underlying malignancy. 

Although not as common as hypercalcemia, tumor lysis syndrome may cause significant morbidity and mortality if adequate prophylaxis and treatment are not instituted. Tumor lysis syndrome is the result of rapid destruction of malignant cells with subsequent release of intracellular contents into the circulation. 

The primary goals of management of tumor lysis syndrome are (1) prevention of renal failure and (2) prevention of electrolyte imbalances. Thus the best treatment for tumor lysis syndrome is prophylaxis to enable delivery of cytotoxic therapy for the underlying malignancy. For patients who present with or develop tumor lysis syndrome despite prophylaxis, treatment goals include (1) decrease uric acid levels, (2) correct electrolyte imbalances, and (3) prevent compromised renal function. These goals should be achieved in a cost-effective manner. 

Prevention of tumor lysis syndrome generally is achieved by increasing the urine output and preventing accumulation of uric acid. Prophylactic strategies should begin immediately on presentation, preferably 48 hours prior to cytotoxic therapy. Treatment modalities primarily increase uric acid solubility, address electrolyte disturbances, and support renal output. 

Prophylaxis and treatment of hyperuricemia associated with tumor lysis syndrome. ALL, acute lymphoblastic leukemia AML, acute myelogenous leukemia IV, intravenous. (Data from refs. 32 and 33.)... 

Pharmacologic prevention strategies for tumor lysis syndrome are aimed at low- and high-risk patients (Fig. 96-7). Allopurinol is a xanthine oxidase inhibitor that is used for prevention only because it has no effect on preexisting elevated uric acid. Rasburicase is a recombinant form of urate oxidase that is useful for both prevention and treatment but is extremely expensive (Table 96-12). Although the approved dose is 0.2 mg/kg per day... 

Khalil A, Chammas M, Shamseddine A, Seoud M. Fatal acute tumor lysis syndrome following treatment of vulvar carciuoma case report. Eur J Gyuaecol Oucol 1998 19(4) 415-16. 

In general, the MoAbs used in treating cancer are relatively well tolerated compared with conventional cytotoxic chemotherapy. The main adverse effect associated with rituximab use is infusion-related or hypersensitivity reactions. Patients may experience fever, rigors, dyspnea, hypotension, and rarely anaphylactoid reactions. Premedication with acetaminophen, diphenhydramine, and corticosteroids can reduce these reactions. Patients with significant tumor burden at the time of first treatment with rituximab may experience tumor lysis syndrome, and appropriate measures should be implemented to prevent this complication in these patients. 

Hyperphosphatemia is not uncommonly observed in patients undergoing treatment for acute leukemia and lymphomas. Chemotherapeutic treatment of acute lymphoblastic leukemia may result in the release of large amounts of phosphorus into the systemic circulation secondary to lysis of lymphoblasts. Initiation of chemotherapy for Burkitt s lymphoma results in a rapid lysis of malignant cells, resulting in hyperphosphatemia, hyperuricemia, hyperkalemia, and hypocalcemia. This syndrome is commonly referred to as tumor lysis syndrome. ... 

Yarpuzlu AA. A review of clinical and laboratory findings and treatment of tumor lysis syndrome. Clinica Chemica Acta 2003 333 13-18. 

HDAC infusions should be administered over 2-3 hours to decrease risk of CNS toxicity use steroid eyedrops during treatment and for 48 hours posttreatment to prevent conjunctivitis with HDAC Increased HDAC neurotoxicity in patients with impaired renal function dose reduction recommended frequent neurologic exams monitor creatinine avoid concurrent administration of nephrotoxic drugs Rapid cell kill may see tumor lysis syndrome with large tumor burden (WBC >100,000/mm3)... 

Risk of opportunistic infections associated with decreased T-cell function for several months after treatment (PCP, mycobacterial infections) prophylactic antibiotics for PCP and HSV should be considered, particularly when fludarabine is used in combination with corticosteroids Rapid cell kill tumor lysis syndrome precautions needed reduce dose with impaired renal function... 

Toxic manifestations include myelosuppression, nausea and vomiting, chills and fever, malaise, anorexia, and weakness. Lymphopenia and thrombocytopenia are dose limiting and possibly cumulative. CD4 T cells are depleted with therapy. Opportunistic infections and tumor lysis syndrome have been reported. Peripheral neuropathy may occur at standard doses. Altered mental status, seizures, optic neuritis, and coma have been observed at higher doses and in older patients. Rarely, CLL patients may develop an acute hemolytic anemia or pure red cell aplasia during fludarabine treatment. Severe pneumonitis responsive to glucocorticoids has been encountered. Because a significant fraction of drug ( 25%) is eliminated in the urine, patients with compromised renal function should be treated with caution, and initial doses should be reduced proportionate to serum creatinine levels. 

Several enzyme therapies are also used in the treatment of cancer. For instance, rasburicase (uricase Elitek EC 1.7.3.3) is used in the treatment of hyperuricemia due to tumor lysis syndrome (TLS). This is a potentially life-threatening condition that is associated with rapidly developing tumors, such as those found in lymphoma and leukemia, in patients undergoing chemotherapy. The incidence of hyperuricemia in these patients is close to 20% [88]. Uricase is an interesting enzyme, because it is found in most mammals, with the exception of humans, where the gene contains a nonsense mutation [89]. Rasburicase is well tolerated, has a very fast onset of action, and is administered intravenously once a day. However, the enzyme cannot be used on patients with glucose-6-phosphate dehydrogenase deficiency [90]. The... 

Indications for renal replacement therapy in the acute setting and for other disease processes are different from those for ESRD. A common mode of ESRD therapy in the outpatient setting is intermittent hemodialysis (IHD) where a patient receives intense treatment over the course of a few hours several times a week. Acute renal failure in the inpatient setting is often treated with continuous renal replacement therapy (CRRT), which is applied for the entire duration of the patient s clinical need and relies upon hemofiltration to a higher degree than IHD (Meyer, 2000). Other nonrenal indications for CRRT are based on the theoretical removal of inflammatory mediators or toxins and elimination of excess fluid (Schetz, 1999). These illnesses include sepsis and systemic inflammatory response syndrome, acute respiratory distress syndrome, congestive heart failure with volume overload, tumor lysis syndrome, crush injury, and genetic metabolic disturbances (Schetz, 1999). 

Reactions following initial infusions of antibody are common, but these can usually be handled by a cautious rate of infusion, appropriate hydration and diuresis, and, if necessary, praned-ication. Twenty six percent of initial reactions are reported to be mild, 48 % moderate, and 26 % severe. The initial infusion reaction to some mAbs, for example, rituximab (see below), may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Tumor lysis syndrome, noted particularly with rituximab, can occur following cancer treatment and sometimes without treatment. It is believed to be the result of breakdown products of cancer cells leading to increased levels of some metabolites and reflected in conditions such as hypercalcemia, hyperkalemia, hyperphosphatemia, acute uric acid nephropathy, and acute renal failure. The syndrome can occur in the early stages of mAb therapy and is potentially life-threatening. Cytokine release syndrome, also called cytokine storm, is commonly seen after... 

A systematic review and meta-analysis reports that besides effective reduction in serum uric acid levels in adults with tumor lysis syndrome by rasburicase, 7.4% of patients developed clinical tumor lysis syndrome (95%C1 1.7-16.7%), 4.4% developed AKI (95%CI 3.0-6.0%) and 2.6% of patients died (95%C1 0.95-5.0%) after rasburicase treatment (different duration and doses reported in the individual studies)[66 ]. 

---