A dose of 175 mg/m2
and a 3 hours infusion schedule. All patients were premedicated to minimize hypersensitivity reactions. Data from these clinical trials demonstrate that Paclitaxel Injection given at this dose and schedule is well tolerated. Myelosuppression. in particular, is less frequent and less severe than with 24 hour infusion schedule. Moreover, as compared to a 24 hour infusion schedule, the incidence of hypersensitivity reaction, peripheral neuropathy or other significant undesirable effects was not increased when Paclitaxel Injection was administered at this dose and schedule.
None of the observed toxicities were influenced by age.
The most frequent significant undesirable effect of Paclitaxel Injection was bone marrow suppression. Severe neutropenia (<500 cells/mm3
) occurred in 27% of patients, but was not associated with febrile episodes. Only 1% of patients experienced severe neutropenia for 7 days or more Eighteen percent of patients had an infectious episode.
Although severe septic episodes associated with severe neutropenia attributable to Paclitaxel Injection were reported in early clinical trials, no severe infections or septic episodes were seen at the recommended dose and infusion schedule.
Thrombocytopenia was reported in 6% of patients. One percent of patients had a platelet low 3 count 50.000/mm3
at least once while on study.
Anemia was observed in 62% of patients, but was severe (Hb<8g/dL) in only 6% of patients.
Incidence and severity of anemia are related to baseline hemoglobin status.
A significant Hypersensitivity reaction (defined as hypotension requiring therapy, angioedema, respiratory distress requiring bronchodilator therapy or generalized urticaria)
occurred in 2 patients. Thirty-nine percent of patients (20% of all courses) experienced minor hypersensitivity reaction. These minor reaction, mainly flushing and rash did not require therapeutic intervention nor did they prevent continuation of Paclitaxel Injection therapy.
Hypotension and bradycardia were experienced by 22% and 3% of patients, respectively, and were asymptomatic in all cases.
Peripheral neuropathy, mainly manifested by paresthesia, affected 64% of patients, but was severe in only 4% of patients. Peripheral neuropathy can occur following the first course and can worsen with increasing exposure to Paclitaxel Injection Sensory symptoms have usually improved or resolved within several months of Paclitaxel Injection discontinuation Preexisting neuropathies resulting from prior therapies are not a contraindication for Paclitaxel Injection therapy.
Arthralgia or myalgia affected 54% of patients and was severe in 12% of patients.
Alopecia was observed in almost all patients.
Gastrointestinal side effects were usually mild to moderate: nausea/vomiting, diarrhoea and mucositis were reported by 44%, 25% and 20% of patients respectively. Other gastrointestinal
events included anorexia (25% of patients) constipation (18%) and intestinal obstruction (4%).
Patients with hepatic impairment may be at increased risk of toxicity, particularly grade III-IV myelosuppression. Dose adjustment is recommended. Severe elevation (>5 x normal values) in AST (SGOT), alkaline phosphate or bilirubin were seen in 5%, 5% and 1% of patients.