Neutropenia paclitaxel

Bone marrow suppression is a dose-limiting adverse effect often encountered with paclitaxel. Neutropenia occurs most commonly 8-10 days after treatment, and recovery usually occurs on days 15-21. Paclitaxel is relatively platelet-sparing, and thrombocytopenia and anemia are rare (26). There is no evidence that neutropenia is cumulative, suggesting that paclitaxel may not irreversibly damage hemopoietic stem cells (1). 

Sissung, T. M., Mross, K., Steinberg, S. M., et al. (2006) Association of ABCBl genotypes with paclitaxel-mediated peripheral neuropathy and neutropenia. Eur. J. Cancer. 42, 2893-2896. 

Paclitaxel Taxol Carcinoma of the breast, ovaries Kaposi sarcoma nonsmall cell lung cancer Blood disorders (anemia, leukopenia, neutropenia, thrombocytopenia] hypersensitivity reaction (skin rash/itching, shortness of breath] joint/muscle pain peripheral neuropathies Gl distress (nausea, vomiting, diarrhea]... 

CYCLOPHOSPHAMIDE PACLITAXEL t risk of neutropenia, thrombocytopenia and mucositis when paditaxel is infused over 24 or 72 hours prior to cyclophosphamide Mechanism is uncertain Administer cyclophosphamide first and then follow with paditaxel... 

DOXORUBICIN PACLITAXEL t risk of neutropenia, stomatitis and cardiomyopathy due to t plasma concentrations of doxorubicin t risk of neutropenia, stomatitis and cardiomyopathy due to t plasma concentrations of doxorubicin when paditaxel is given before doxorubicin Doxorubicin should be administered prior to paditaxel. The cumulative dose of doxorubicin should be limited to 360 mg/m2 when concurrently administered with paditaxel... 

PACLITAXEL CISPLATIN t risk of profound neutropenia Prior administration of cisplatin tends to impair renal function and 1 clearance of paclitaxel by approximately 25% Advise administration of paclitaxel prior to cisplatin... 

Neutropenia is dose- and schedule-related and is less common with shorter infusion schedules. At doses of 110-250 mg/m over 24 hours, neutropenia is usually severe, and grade 4 neutropenia develops in a large proportion of patients. Paclitaxel given as a 3-hour infusion causes less severe neutropenia (17,24,29). An analysis of patients receiving either a 3-hour or 24-hour infusion of 175 or 135 mg/m showed that severe neutropenia was more common with the 24-hour infusions 75% of patients developed severe neutropenia (absolute neutrophil count below 500 X 10 /1) and episodes of fever (29). Doses of 200-250 mg/m also cause severe neutropenia when paclitaxel was given as a 24-hour infusion, but recovery of neutrophil count was fairly rapid (13,14,26,33,36,37). 

The duration of neutropenia is usually brief and treatment delays for unresolved adverse hematological effects at day 21 are rare. Paclitaxel-induced neutropenia does not always lead to infectious complications, and therefore... 

Other data suggest that neutropenia may be related to pharmacological exposure, and phase 1 studies have shown that the severity of paclitaxel-induced neutropenia correlates with the area under the paclitaxel concentration-time curve (36). 

The incidence of neutropenia has also been investigated in combination schedules. Patients receiving paclitaxel in combination with cyclophosphamide have severe neutropenia more often than with single treatment (72% of patients). Paclitaxel given as a 24-hour infusion before cyclophosphamide is more likely to cause severe neutropenia compared with patients who receive cyclophosphamide first (31). 

There is some evidence that there is a clinically significant pharmacokinetic interaction of paclitaxel with cisplatin. When cisplatin was given before pachtaxel, the clearance rate of paclitaxel was 25% less than when the two drugs were given in the opposite sequence. In consequence, neutropenia was more profound with the former schedule (281). In addition, in experimental studies, cytotoxicity increased when human ovarian carcinoma cells were... 

G. J. Fetterly, J. M. Tamburhn, and R. M. Stranbinger, Paclitaxel pharmacodynamics application of mechanism-based neutropenia model. Biopharm Drug Dispos 22 251-261... 

Neurotoxicity may be severe enough to require discontinuation treat myalgias/arthralgias with NSAIDs, narcotic analgesics In paclitaxel-cisplatin combination regimens, give paclitaxel first to decrease neutropenia... 

Paclitaxel exerts its primary toxic effects on the bone marrow. Neutropenia usually occurs... 

Toxicity Paclitaxel causes neutropenia, thrombocytopenia, a high incidence of peripheral neuropathy, and possible hypersensitivity reactions during infusion. Docetaxel causes neurotoxicity and bone marrow depression. 

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