Docetaxel

Patients with an absolute neutrophil count 3 should not receive docetaxel. Monitor blood counts frequently to monitor for neutropenia (which may be severe and result in infection). The dose-limiting toxicity is neutropenia. Platelets should recover to >100,000/mm3 prior to treatment. Patients with increased liver function tests experienced more episodes of neutropenia with a greater number of severe infections; monitor liver function tests frequently. Hematologic toxicity may require dose reduction or therapy discontinuation.

Cutaneous reactions, including erythema (with edema) and desquamation, have been reported; may require dose reduction.

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

Severe fluid retention, characterized by pleural effusion (requiring immediate drainage), ascites with pronounced abdominal distention, peripheral edema (poorly tolerated), dyspnea at rest, cardiac tamponade, generalized edema, and weight gain, has been reported (despite the use of premedication with 3 days of dexamethasone). Fluid retention may begin as lower extremity peripheral edema and become generalized with a median weight gain of 2 kg. In patients with breast cancer, the median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m2; fluid retention resolves in a median of 16 weeks after discontinuation. Patients should be premedicated with a corticosteroid (starting 1 day prior to administration) to reduce the incidence and severity of fluid retention. Closely monitor patients with existing effusions.

Severe hypersensitivity reactions, characterized by generalized rash/erythema, hypotension, bronchospasms, or rare anaphylaxis may occur (may be fatal; has occurred in patients receiving a 3-day corticosteroid premedication). Hypersensitivity reactions require immediate discontinuation of the docetaxel infusion and administration of appropriate therapy. Do not administer to patients with a history of severe hypersensitivity to docetaxel or polysorbate 80. Minor reactions including flushing or localized skin reactions may also occur. Observe for hypersensitivity, especially with the first 2 infusions. Discontinue for severe reactions; do not rechallenge if severe. Patients should be premedicated with a corticosteroid (starting 1 day prior to administration) to prevent or reduce the severity of hypersensitivity reactions.

Dosage adjustment is recommended with severe neurosensory symptoms (paresthesia, dysesthesia, pain); persistent symptoms may require discontinuation. Reversal of symptoms may be delayed after discontinuation.

Cystoid macular edema (CME) has been reported; if vision impairment occurs, a prompt comprehensive ophthalmic exam is recommended. If CME is diagnosed, initiate appropriate CME management and discontinue docetaxel (consider non-taxane treatments). In a study of patients receiving docetaxel for the adjuvant treatment of breast cancer, a majority of patients experienced tearing, which occurred in patients with and without lacrimal duct obstruction at baseline. Onset was generally after cycle 1, but subsided in most patients within 4 months after therapy completion (Chan 2013).

Treatment-related acute myeloid leukemia or myelodysplasia occurred in patients receiving docetaxel in combination with anthracyclines and/or cyclophosphamide.

Patients with abnormal liver function, those receiving higher doses, and patients with non–small cell lung cancer and a history of prior treatment with platinum derivatives who receive single-agent docetaxel at a dose of 100 mg/m2 are at higher risk for treatment-related mortality.

Fatigue and weakness (may be severe) have been reported; symptoms may last a few days up to several weeks. In patients with progressive disease, weakness may be associated with a decrease in performance status. Disease-related concerns:

In a scientific statement from the American Heart Association, docetaxel has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

Avoid use in patients with bilirubin exceeding upper limit of normal (ULN) or AST and/or ALT >1.5 times ULN in conjunction with alkaline phosphatase >2.5 times ULN. Patients with bilirubin elevations or abnormal transaminases (with concurrent abnormal alkaline phosphatase) are at increased risk for grade 4 neutropenia, neutropenic fever, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated transaminase elevations >1.5 times ULN also had a higher rate of grade 4 neutropenic fever, although no increased incidence of toxic death. Monitor bilirubin, AST or ALT, and alkaline phosphatase prior to each docetaxel cycle. The alcohol content of the docetaxel formulation should be taken into account when administering to patients with hepatic 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. Dosage form specific issues:

Some docetaxel formulations contain alcohol (content varies by formulation), which may affect the central nervous system and cause symptoms of alcohol intoxication. Consider alcohol content and use with caution in patients for whom alcohol intake should be avoided or minimized. Patients should avoid driving or operating machinery immediately after the infusion. An FDA-approved non-alcohol generic formulation (20 mg/mL) is available.

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling. Other warnings/precautions:

Premedication with oral corticosteroids is recommended to decrease the incidence and severity of fluid retention and severity of hypersensitivity reactions. The manufacturer recommends dexamethasone 16 mg/day (8 mg twice daily) orally for 3 days, starting the day before docetaxel administration; for prostate cancer, when prednisone is part of the antineoplastic regimen, dexamethasone 8 mg orally is administered at 12 hours, 3 hours, and 1 hour prior to docetaxel.