What are the side effects of Paclitaxel?

From the Guidelines

Paclitaxel has several common side effects, including hair loss, bone marrow suppression, peripheral neuropathy, muscle and joint pain, nausea, vomiting, and diarrhea, as reported in studies such as 1 and 1. The most frequent side effects of paclitaxel include:

• Hair loss
• Bone marrow suppression (leading to low white blood cell counts, anemia, and reduced platelets)
• Peripheral neuropathy (numbness, tingling, or pain in hands and feet)
• Muscle and joint pain
• Nausea, vomiting, and diarrhea Some patients experience allergic reactions, which is why premedication with steroids and antihistamines is typically given before paclitaxel administration, as noted in 1. Cardiac issues such as abnormal heart rhythms or decreased blood pressure can occur during infusion. Paclitaxel may also cause nail changes, mouth sores, fatigue, and liver enzyme elevations. These side effects occur because paclitaxel works by interfering with cell division, affecting both cancer cells and normal rapidly dividing cells in the body. The severity of side effects varies between individuals and depends on dosage, which typically ranges from 135-175 mg/m² given every three weeks or in weekly regimens of 80-100 mg/m², as seen in studies such as 1 and 1. Patients should immediately report severe allergic reactions, unusual bleeding, severe neuropathy, or signs of infection to their healthcare provider. It's worth noting that the side effects of paclitaxel can be managed with proper care and treatment, and patients should discuss any concerns with their healthcare provider, as recommended in 1 and 1.

From the FDA Drug Label

Neurologic: The assessment of neurologic toxicity was conducted differently among the studies as evident from the data reported in each individual study. Moreover, the frequency and severity of neurologic manifestations were influenced by prior and/or concomitant therapy with neurotoxic agents In general, the frequency and severity of neurologic manifestations were dose-dependent in patients receiving single-agency paclitaxel. Peripheral neuropathy was observed in 60% of all patients (3% severe) and in 52% (2% severe) of the patients without pre-existing neuropathy.

Arthralgia/Myalgia: There was no consistent relationship between dose or schedule of paclitaxel and the frequency or severity of arthralgia/myalgia. Sixty percent of all patients treated experienced arthralgia/myalgia; 8% experienced severe symptoms

Hepatic: No relationship was observed between liver function abnormalities and either dose or Schedule of paclitaxel administration Among patients with normal baseline liver function 7%, 22%, and 19% had elevations in bilirubin, alkaline phosphatase, and AST (SGOT), respectively.

Renal: Among the patients treated for Kaposi’s sarcoma with paclitaxel, 5 patients had renal toxicity of grade III or IV severity.

Gastrointestinal (GI): Nausea/vomiting, diarrhea, and mucositis were reported by 52%, 38%, and 31% of all patients, respectively

Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2% to 4% of patients receiving paclitaxel in clinical trials.

The side effects of Paclitaxel include:

• Neurologic effects:
  • Peripheral neuropathy (60% of patients, 3% severe)
  • Paresthesia
  • Neuromotor and neurosensory events
  • Grand mal seizures
  • Syncope
  • Ataxia
  • Neuroencephalopathy
• Arthralgia/Myalgia:
  • 60% of patients experienced arthralgia/myalgia
  • 8% experienced severe symptoms
• Hepatic effects:
  • Elevations in bilirubin (7% of patients)
  • Elevations in alkaline phosphatase (22% of patients)
  • Elevations in AST (SGOT) (19% of patients)
• Renal effects:
  • Renal toxicity of grade III or IV severity (5 patients)
• Gastrointestinal (GI) effects:
  • Nausea/vomiting (52% of patients)
  • Diarrhea (38% of patients)
  • Mucositis (31% of patients)
• Hypersensitivity reactions:
  • Anaphylaxis
  • Severe hypersensitivity reactions (2% to 4% of patients)
  • Angioedema
  • Generalized urticaria 2, 2, 2

From the Research

Side Effects of Paclitaxel

The side effects of Paclitaxel are numerous and can be severe. Some of the most common side effects include:

• Peripheral neuropathy, which can occur in up to 60-70% of chemotherapy patients 3, 4
• Myelosuppression, which is the dose-limiting toxicity of paclitaxel when administered on a prolonged infusion schedule 5
• Neuropathy, which is more common with short infusions 5
• Pain and numbness in hands and feet due to paclitaxel accumulation in the dorsal root ganglia 4
• Length-dependent axonal sensory neuropathy, where axons are symmetrically damaged and die back 4
• Microtubule stabilization, which disrupts axonal transport, leading to ATP undersupply and oxidative stress 4
• Mitochondria morphology alteration during paclitaxel treatment 4
• Inflammation in the spinal cord as well as the dorsal root ganglia, which is a key player in pain sensation and axonal damage 4

Prevention and Treatment of Paclitaxel-Induced Peripheral Neuropathy

There are some potential strategies for preventing and treating paclitaxel-induced peripheral neuropathy, including:

• Concomitant use of α1-receptor antagonists, which may moderate the development of peripheral neuropathy 6
• Use of neuroprotective agents, which have been tested in animal and clinical studies to prevent paclitaxel neurotoxicity 7
• Development of novel paclitaxel formulations, which aim to minimize toxicities 7