Paclitaxel

Bone marrow suppression (primarily neutropenia; may be severe or result in infection) may occur. Monitor blood counts frequently. Do not administer if baseline neutrophil count is 3 (for solid tumors) or 3 (for patients with AIDS-related Kaposi sarcoma). Bone marrow suppression (usually neutropenia) is dose-dependent and is the dose-limiting toxicity; neutrophil nadir is usually at a median of 11 days. Subsequent cycles should not be administered until neutrophils are >1,500/mm3 (for solid tumors) and 1,000/mm3 (for Kaposi sarcoma); platelets should recover to 100,000/mm3. Reduce future doses by 20% for severe neutropenia (3 for 7 days or more) and consider the use of supportive therapy, including growth factor treatment.

Infusion-related hypotension, bradycardia, and/or hypertension may occur; frequent monitoring of vital signs is recommended, especially during the first hour of the infusion. Rare but severe conduction abnormalities have been reported; conduct continuous cardiac monitoring during subsequent infusions for these patients. In a scientific statement from the American Heart Association, conventional paclitaxel has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016])

Paclitaxel is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Injection-site reactions are generally mild (skin discoloration, tenderness, erythema, or swelling) and occur more commonly with an extended infusion duration (eg, 24 hours); injection-site reactions may be delayed (7 to 10 days). More severe reactions (phlebitis, cellulitis, skin exfoliation, necrosis, fibrosis, and induration) have also been reported. Recall skin reactions may occur despite administering through a different IV site.

Anaphylaxis and severe hypersensitivity reactions (dyspnea requiring bronchodilators, hypotension requiring treatment, angioedema, and/or generalized urticaria) have occurred in 2% to 4% of patients in clinical studies. Premedicate with corticosteroids, diphenhydramine, and H2 antagonists prior to infusion. Some reactions have been fatal despite premedication. If severe hypersensitivity occurs, stop infusion and do not rechallenge. Minor hypersensitivity reactions (flushing, skin reactions, dyspnea, hypotension, or tachycardia) do not require interruption of treatment.

Peripheral neuropathy may commonly occur; patients with preexisting neuropathies from prior chemotherapy or coexisting conditions (eg, diabetes mellitus) may be at a higher risk; reduce dose by 20% for severe neuropathy. Disease-related concerns:

Use with extreme caution in patients with hepatic dysfunction (myelotoxicity may be worsened in patients with total bilirubin >2 times ULN); dose reductions are recommended. 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:

Use with caution in the elderly; increased risk of toxicity (severe neutropenia, neuropathy, and cardiovascular events). Other warnings/precautions:

Conventional paclitaxel formulations contain polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), which is associated with hypersensitivity reactions. Formulations also contain dehydrated alcohol which may cause adverse CNS effects.

Should be administered under the supervision of an experienced cancer chemotherapy physician. Administer in a facility sufficient to appropriately diagnose and manage complications.

Intraperitoneal administration of paclitaxel is associated with a higher incidence of chemotherapy- related toxicity (Armstrong 2006).