Oxaliplatin

Grade 3 and 4 neutropenia occurs commonly with oxaliplatin in combination with fluorouracil and leucovorin; sepsis, neutropenic sepsis, and septic shock have been reported with oxaliplatin (some fatal). Delay oxaliplatin treatment until neutrophils are ≥1500/mm3; withhold treatment for sepsis or septic shock. Reduce the dose after recovery from grade 4 neutropenia or neutropenic fever.

QT prolongation and ventricular arrhythmias, including fatal torsades de pointes have been reported in postmarketing surveillance. ECG monitoring is recommend in patients with heart failure, bradyarrhythmias, concomitant medications known to cause QT prolongation (including class Ia and III antiarrhythmics), and electrolyte abnormalities. Avoid use in patients with congenital long QT syndrome. Monitor potassium and magnesium prior to and periodically during treatment; correct hypokalemia and hypomagnesemia prior to treatment initiation.

Oxaliplatin is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Oxaliplatin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016). Fluorouracil and leucovorin are associated with GI adverse events; the incidence of GI toxicity is increased when oxaliplatin is administered with fluorouracil and leucovorin. Mucositis, stomatitis, GI bleeding, and GI obstruction have been reported.

Anaphylactic reactions have been reported with oxaliplatin (may occur within minutes of administration); symptoms may be managed with epinephrine, corticosteroids, antihistamines, and discontinuation; oxygen and bronchodilators have also been used (Kim 2009). Grade 3 or 4 hypersensitivity has been observed. Allergic reactions are similar to reactions reported with other platinum analogs and may occur with any cycle. Reactions typically occur after multiple cycles; in retrospective reviews, reaction occurred at a median of 7 to 9 cycles, with an onset of 5 to 70 minutes (Kim 2009; Polyzos 2009). Symptoms may include bronchospasm (rare), erythema, hypotension (rare), pruritus, rash, and/or urticaria; previously-untreated patients have also experienced flushing, diaphoresis, diarrhea, shortness of breath, chest pain, hypotension, syncope, and disorientation. According to the manufacturer, rechallenge is contraindicated (deaths due to anaphylaxis have been associated with platinum derivatives). In patients rechallenged after mild hypersensitivity, reaction recurred at a higher level of severity; for patients with severe hypersensitivity, rechallenge (with 2 to 3 days of antihistamine and corticosteroid premedication, and prolongation of infusion time) allowed for 2 to 4 additional oxaliplatin cycles; however, rechallenge was not feasible in nearly two-thirds of patients due to the severity of the initial reaction (Polyzos 2009).

Hepatotoxicity (including rare cases of hepatitis and hepatic failure) has been reported. Liver biopsy has revealed peliosis, idiopathic noncirrhotic portal hypertension (including nodular regenerative hyperplasia), sinusoidal alterations, perisinusoidal fibrosis, and veno-occlusive lesions. The presence of hepatic vascular disorders (including veno-occlusive disease) should be considered, especially in individuals developing portal hypertension or who present with increased liver function tests.

Two different types of peripheral sensory neuropathy may occur: The first type of neuropathy is an acute presentation (within hours to 1 to 2 days), reversible (resolves within 14 days), with primarily peripheral symptoms that are often exacerbated by cold (may include pharyngolaryngeal dysesthesia); avoid mucositis prophylaxis with ice chips, exposure to cold temperatures, or consumption of cold food/beverages during or within hours after oxaliplatin infusion (may exacerbate symptoms); this acute neuropathy commonly recurs with subsequent doses. Cold-triggered neuropathy may last up to 7 days after oxaliplatin administration (Grothey 2011). The second type of neuropathy is a more persistent (>14 days) presentation that often interferes with daily activities (eg, writing, buttoning, swallowing); these symptoms may improve in some patients upon discontinuing treatment. In a retrospective evaluation of patients treated with oxaliplatin for colorectal cancer, the incidence of peripheral sensory neuropathy was similar between diabetic and nondiabetic patients (Ramanathan 2010). Several retrospective studies (as well as a small, underpowered randomized trial) have suggested calcium and magnesium infusions before and after oxaliplatin administration may reduce incidence of cumulative sensory neuropathy; however, a recent abstract of an ongoing randomized, placebo-controlled, double-blind study in patients with colorectal cancer suggests there is no benefit of calcium and magnesium

May cause pulmonary fibrosis (may be fatal); withhold treatment for unexplained pulmonary symptoms (eg, crackles, dyspnea, nonproductive cough, pulmonary infiltrates) until interstitial lung disease or pulmonary fibrosis are excluded.

Cases of reversible posterior leukoencephalopathy syndrome (RPLS) have been reported. Signs/symptoms include headache, mental status changes, seizure, blurred vision, blindness and/or other vision changes; may be associated with hypertension. Diagnosis is confirmed with brain imaging.

Rhabdomyolysis (including fatal cases) has been reported with oxaliplatin. Discontinue if signs/symptoms of rhabdomyolysis occur. Disease-related concerns:

Use with caution in patients with renal impairment; increased toxicity may occur. Reduce initial dose in severe impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Elderly patients are more sensitive to adverse events, particularly diarrhea, dehydration, hypokalemia, leukopenia, fatigue, and syncope. Other warnings/precautions:

Oxaliplatin is for IV administration. Administration via the intraperitoneal route (not an approved administration route) is associated with peritoneal hemorrhage and hemorrhagic complications (Charrier 2016).