Paclitaxel Metabolization (chemotherapy) and toxicity
Paclitaxel is an antineoplastic drug that is widely used in first-line chemotherapeutic treatments in cancers of the breast, ovary, lung and prostate, among other solid tumors.
Paclitaxel is a taxoid based antineoplastic drug that stimulates the assembly of microtubules from tubulin dimers and stabilizes microtubules preventing depolymerization.
It inhibits the formation of the mitotic spindle in cell division, blocking the process of mitosis.
Paclitaxel is contraindicated in patients with hypersensitivity to taxoids, in breast-feeding women, when the baseline neutrophil count is less than 1,500/mm3 (<1,000/mm3 for patients with Kaposi's sarcoma); in patients with Kaposi's sarcoma and in patients suffering concurrent, severe and uncontrolled infections.
The use of paclitaxel requires a close hematological, hepatic and cardiac control. Its use is not recommended in patients under 18 years old, and in patients older than 75 years old who received paclitaxel in combination with gemcitabine due to an increased risk of adverse reactions.
Contraceptive methods should be used during and after treatment.
Do not co-administer erlotinib with paclitaxel and gemcitabine.
Paclitaxel should be discontinued in case of developing hypersensitivity reactions and/or sensory neuropathy.
Caution should be exercised in the use of paclitaxel in cases of hepatic insufficiency, myelosuppression and peripheral neuropathy.
In combination with radiotherapy in lung carcinoma, paclitaxel may contribute to the development of interstitial pneumonitis.
If mucositis appears in patients with Kaposi's sarcoma, the dose of paclitaxel should be reduced by 25%. Avoid IA (intra-articular) administration and extravasation.
In patients treated in monotherapy or in combination with gemcitabine, there is a risk of pneumonitis and sepsis (the patient should be monitored).
In metastatic breast cancer and non-small cell lung cancer with moderate to severe hepatic impairment it is recommended to reduce the dose by 20%.
Treatment with paclitaxel can develop a state of immunosuppression that can cause different types of infection (infection of the urinary tract, folliculitis, infection of the upper respiratory tract, candidiasis, sinusitis). Treatment with paclitaxel can also cause neutropenia, anemia, leukopenia, thrombocytopenia, lymphopenia, myelosuppression.
Treatment with paclitaxel can cause a decrease in hematocrit, a decrease in the number of red blood cells and other blood disorders such as disseminated intravascular coagulation.
Other side effects are: anorexia, dehydration, decreased appetite, hydroelectrolyte alterations (hypokalemia), insomnia, depression, anxiety, vertigo.
Treatment with paclitaxel can cause peripheral neuropathy, hypoaesthesia, paresthesia, peripheral sensory neuropathy, headache, dysgeusia, dizziness, peripheral motor neuropathy, ataxia, sensory disorders, somnolence.
Other side effects are: increased lacrimation, blurred vision, dry eye, dry keratoconjunctivitis, madarosis.
Other signs and symptoms of treatment with paclitaxel can be lymphedema, dyspnea, epistaxis, pharyngolaryngeal pain, cough, rhinitis, rhinorrhea, nausea, diarrhea, vomiting, constipation, stomatitis, abdominal pain, abdominal distension, upper abdominal pain, dyspepsia, gastroesophageal reflux, oral hypoaesthesia, alopecia, rash, nail disorders, pruritus, dry skin, erythema, pigmentation/discoloration of the nails, hyperpigmentation of the skin, onycholysis, changes in the nails.
Other side effects are: Arthralgia, myalgia, pain in the extremities, bone pain, back pain, muscle cramps, pain in the limbs; fatigue, asthenia, pyrexia, peripheral edema, mucosal inflammation, pain, rigor, edema, weakness, decreased functional status, chest pain, flu-like illness, malaise, lethargy, hyperpyrexia, weight loss.
Treatment with paclitaxel may produce an increase in liver and pancreatic enzymes (ALT, AST, GGT, alkaline phosphatase) in the blood. In addition paclitaxel increases the body temperature.
The use of the following substances in concomitancy with paclitaxel may increase its toxicity and therefore caution is advised: known cytochrome CYP2C8 or CYP3A4 inhibitors (for example: ketoconazole and imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir and nelfinavir).
The efficacy of paclitaxel may be diminished by its concomitant use with: known CYP2C8 cytochrome or cytochrome CYP3A4 inducers (eg, rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine).
- Taxol ®
Gene or region studied