Taxanes Chemotherapy Summary

	Paclitaxel (Taxol)	Docetaxel (Taxotere)	Nab-Paclitaxel (Abraxane)	Cabazitaxel (Jevtana)
Classification	Taxane (Anti-microtubule agent)
Drug Manufacturer	Bristol-Myers Squibb	Sanofi-aventis	Abraxis	Sanofi-aventis
Mechanism of Action	·         Cell cycle–specific, active in the mitosis (M) phase of the cell cycle ·         High-affinity binding to microtubules enhances tubulin polymerization leading to inhibition of mitosis and cell division
Absorption	Poorly soluble and not orally bioavailable
Distribution	All body tissues including third space fluid collections EXCEPT CNS & TESTIS			All body tissues & Penetrates blood brain barrier
Metabolism	·         hepatic P450 microsomal system ·         70%–80% of drug is excreted via fecal elimination ·         <10% renal clearance
Half Life	9-50 hrs depending on administration schedule.	11 hours	27 hours	77 hours
Indications	Ovarian, breast, lung, head & neck, bladder, Kaposi	Breast, Lung, Prostate, Gastric, Head & neck, Ovarian, uterine	Breast, Pancreas	Castration resistant Prostate ca
Dosage Range	·         135-175 mg/m2 IV over 3hrs ·         40-80mg/m2 weekly over 1 hr	·         60-100 mg/m2 over 1 hour infusion	·         100-260 mg/m2 IV over 1 hr	·         25 mg/m 2 IV over 1 hr
Drug Interaction	·         Radiation: Paclitaxel & Docetaxel are radiosensitizing agents. ·         Inhibitors and/or activators of the liver cytochrome P450: Concurrent use with drugs such as cyclosporine, ketoconazole, erythromycin & anticonvulsants affect plasma concentration and clearance of Taxanes ·         Platinums: Myelosuppression is greater when platinum compound is administered before Paclitaxel. Platinum compounds inhibit plasma clearance of Paclitaxel. When a platinum analog is used in combination, Paclitaxel must be given first. ·         Cyclophosphamide: Myelosuppression is greater when Cyclophosphamide is administered before Paclitaxel. ·         Doxorubicin: Paclitaxel reduces the plasma clearance of doxorubicin by 30%–35%, resulting in increased severity of myelosuppression ·         Abraxane drug interactions not well characterized to date
Toxicity	Myelosuppression: ·         Dose-limiting neutropenia with nadir at day 8–10 and recovery by day 15–21. ·         Decreased incidence of neutropenia with 3-hour schedule when compared to 24-hour schedule Hypersensitivity: ·         Occurs in 20-40% of patients, occurs within the first 2–3 minutes of an infusion and almost always within the first 10 minutes.  the cremaphor solvent contributes significantly to this reaction Neurotoxicity: ·         Mainly sensory neuropathy with numbness and paresthesias. ·         Dose dependent effect ·         Motor and autonomic neuropathy observed at high doses. Sinus bradycardia: ·         30% of patients ·         Transient asymptomatic Alopecia: ·         Loss of total body hair in almost all patients Mucositis and diarrhea: ·         30-40% of patients Transient elevation of LFTs Onycholysis ·         >6 courses on the weekly schedule ·         Not with every 3-week’s schedule ·         Avoid sun exposure to skin & nails.	Myelosuppression: ·         Dose-limiting neutropenia with nadir at day 7–10 and recovery by day 14. ·         Thrombocytopenia & anemia are also observed Hypersensitivity: ·         Occurs within the first 2–3 minutes of an infusion and almost always within the first 10 minutes.  Fluid retention syndrome: ·         Peripheral and/or generalized edema, pleural effusion and ascites ·         Incidence increases with total doses >400 mg/m2 ·        Occurs in about 50% of patients Maculopapular skin rash & dry itchy skin: ·         Affects more arms and hands ·         Brown discoloration of fingernails may occur ·        Observed in up to 50% of patients within 1 week of therapy Alopecia: ·         80% of patients Mucositis & diarrhea: ·        40% of patients Peripheral Neuropathy: ·        Less observed than with Taxol Fatigue & asthenia: ·         Occurs in 60-70% of patients. Arthralgia and myalgia	Myelosuppression: ·         Dose-limiting neutropenia. ·         Anemia & thrombocytopenia relatively uncommon Neurotoxicity: ·         Mainly sensory neuropathy with numbness and paresthesias. ·         Dose dependent effect ·         In contrast to Paclitaxel more readily reversible Ocular and visual disturbances: ·         Seen in 13% of pts. With severe cases in 1% Fatigue & asthenia: Alopecia: ·         Loss of total body hair in almost all patients Mucositis and diarrhea: ·         Mild, seen in 10% of Pts. Transient elevation of LFTs Injection site reactions Cardiac toxicity ·         chest pain, SVT, HTN	Myelosuppression: ·         Dose-limiting neutropenia. ·         Anemia & thrombocytopenia are also observed. Hypersensitivity: Diarrhea, N,V, loss of appetite: Fatigue & asthenia: Neurotoxicity: ·         In the form of peripheral neuropathy, dizziness Arthralgia and myalgia Cardiac toxicity ·         chest pain, SVT, HTN Alopecia: ·         10% of patients Hematuria and dysuria
Special Considerations	·         The dose should be reduced by 50% if Bil. >1.5 mg/dl and withheld with severe liver dysfunction ·         Use with caution in patients with cardiac conductive system abnormalities ·         Premedication to prevent the incidence of hypersensitivity reactions (HSR). Give Dexamethasone 20 mg PO at 12 and 6 hours before drug administration, Diphenhydramine 50 mg IV, and Cimetidine 300 mg IV at 30 minutes before drug administration. ·         Patients experiencing major HSR may be rechallenged after receiving multiple high doses of steroids	·         Patients with abnormal Liver function are at higher risk for toxicity and drug related mortality ·         Should not be given with ANC of <1500 cells/mm3 ·         Steroid premedication to reduce incidence & severity of fluid retention & hypersensitivity. You should give Decadron 8 mg BID for 3 days starting 1 day prior to drug administration	·         Should not be given with ANC of <1500 cells/mm3 ·         Abraxane has not been studied in patients with hepatic or renal dysfunction. ·         No premedication is required to prevent hypersensitivity reactions prior to administration ·         Can NOT be substituted for or with other Paclitaxel formulations	·         Should not be given with ANC of <1500 cells/mm3 ·         Premedication with IV doses of an antihistamine, corticosteroid, and an H2-antagonist to prevent the incidence of hypersensitivity ·         Contraindicated in patients with hepatic dysfunction (total bilirubin ≥ ULN, AST and/or ALT≥ 1.5 X ULN)