Highly hydrophobic and includes a combination of polyethylated castor oil and ethanol as the vehicle.
Tradename Taxol.
Main limiting toxicity associated with cumulative weekly doses is peripheral neuropathy.
Chemotherapy induced peripheral neuropathy affects up to 70% of patients treated with paclitaxel, and approximately 30% experience severe symptoms.
Chemotherapy induced neuropathy can last for years and significantly diminishes quality of life.
Paclitaxel acts directly on peripheral sensory axons to cause axons degeneration by reducing axonal levels of the protective protein Bclw.
Paclitaxel treatment impairs the transport of specialized RNA granules along with microtubules in axons.
Acts by stabilizing microtubules, leading to cell cycle arrest and cell death.
RNA granules contain the messenger RNA that encodes Bclw and paclitaxel prevents the production of Bclw protein in axons.
Hypersensitivity reactions characterized by dyspnea and hypotension and anaphylaxis can occur.
Angioedema and generalized urticaria reported in 2-4% of patients.
Fatal hypersensitivity reactions have occurred despite premedications.
Causes hypersensitivity reactions on the first administration in up to 40% of patients.
Premedicating patients reduces the likelihood of hypersensitivity reaction to less than 10%.
Hypersensitivity reactions are non immunoglobulin IgG mediated, and skin tests are not useful to predict such reactions.
In metastatic breast cancer weekly dosing has a higher response rate then once every week treatment schedule, but there was no difference in time to progression or overall survival (V2242ill MW et al).
In a phase 3 trial of metastatic breast cancer weekly treatment was associated with a higher response rate and increased time to progression and oral survival then every three week administration of the same drug (Seidman AD et al).
Indicated after failure of combination chemotherapy for metastatic breast cancer or for relapse within six months of adjuvant chemotherapy.
Indicated as first line and subsequent therapy for metastatic ovarian cancer, in combination with cisplatin.
Indicated for non-small cell lung cancer in combination with cisplatin.
Indicated as second line treatment for AIDS-related Kaposi’s sarcoma.