By Dr Tomislav Meštrović, MD, PhD
Two major side-effects of paclitaxel therapy are frequent hypersensitivity reactions and neuropathy. Standard paclitaxel contains Cremophor EL as a solvent, thus requiring premedication with high doses of antihistamines and corticosteroids, as well as prolonged infusion times. Albumin-bound or nab-paclitaxel was developed to overcome such limitations, and also to ensure more convenient drug administration and improve toxicity profiles.
Early development of paclitaxel was hampered by the high incidence of major hypersensitivity reactions, which in some studies approached 30 percent. Initial observations pointed to the histamine and other vasoactive substances as culprits in the development of hypersensitivity reactions.
A majority of affected individuals presented with type 1 hypersensitivity reactions have primarily shown signs of dyspnea, urticaria and hypotension. Other common symptoms included chest or back pain, excess perspiration or sweating and pruritus.
Oral pre-medication with dexamethasone given orally at 12 and 6 hours before infusion of paclitaxel has been shown to significantly reduce the incidence of paclitaxel-induced hypersensitivity reactions. In addition, patients suffering from major hypersensitivity reactions rechallenged with paclitaxel after receiving high doses of corticosteroids have been free of recurrences, although universal success of this approach has not been demonstrated.
Paclitaxel is able to induce a peripheral neuropathy characterized by sensory symptoms such as paresthesia and numbness in a glove-and-stocking distribution. Symmetrical loss of sensations (proprioception, vibration, pinprick and temperature) is also frequently noted.
Symptoms usually occur between 24 and 72 hours upon treatment with higher doses of the drug (>250 mg per square meter), although they usually occur after multiple courses at conventional dosage protocols (<200 mg per square meter). Severe neurotoxicity is quite rare when administering conventional doses – even in patients with prior exposure neurotoxic agents (such as cisplatin). When severe neurotoxicity ensues, it precludes further administration of high doses of the drug for up to 24 hours.
Autonomic and motor dysfunction can also represent a problem of paclitaxel therapy, namely in patients with preexisting neuropathies caused by alcoholism, diabetes mellitus and other pathological conditions. Optic nerve can be affected as well, denoted by scintillating scotoma. When it comes to nab-paclitaxel-induced sensory neuropathy, prior history of chemotherapy and dosing schedule are important factors in the development of the disorder.
There is a common occurrence of transient myalgia (muscle pain), usually observed two to five days after therapy at doses above 170 mg per square meter. Insidious myopathy has been observed with high doses of paclitaxel, often in combination with aforementioned cisplatin.
Other common side-effects
One of the principal toxic effects of paclitaxel is a non-cumulative neutropenia (abnormally low count of neutrophils), suggesting that immature hematopoietic cells are not irreversibly damaged. The drug can also reduce the number of erythrocytes resulting in anemia, as well as thrombocytes which can result in bruising and bleeding.
Normal cardiac rhythm can be disturbed, and the most common manifestation is transient asymptomatic bradycardia. Albeit rare, various arrhythmias, ventricular tachycardia, cardiac ischemia and myocardial infarction have also been noted. Cardiac monitoring is thus advisable for patients with ventricular dysfunction and those who may not be able to fully tolerate the drug's potential bradyarrhythmia.
Gastrointestinal effects such as diarrhea and vomiting are also frequent, particularly upon administration of higher doses. Such conditions necessitate at least two liters of fluids every day. Patients with leukemia are especially prone to mucositis and breakdown of the mucosal barrier.
Akin to the effect of other chemotherapeutic agents, eyelashes, eyebrows and other body hair is often temporarily lost. The process usually starts after first or second cycle of chemotherapy. Inflammation at the injection site (along the course of the vein) and in areas where the drug leaves the blood vessel may rarely occur, as well as the consequent inflammatory skin reactions.
Last Updated: Oct 21, 2014