Bone marrow suppression was the major dose-limiting toxicity of paclitaxel. Neutropenia, the most important hematologic toxicity, was dose and schedule dependent and was generally rapidly reversible. Among patients treated in the Phase 3 second line ovarian study with a 3-hour infusion, neutrophil counts declined below 500 cells/mm 3in 14% of the patients treated with a dose of 135 mg/m 2compared to 27% at a dose of 175 mg/m 2(p=0.05). In the same study, severe neutropenia (<500 cells/mm 3) was more frequent with the 24-hour than with the 3-hour infusion; infusion duration had a greater impact on myelosuppression than dose. Neutropenia did not appear to increase with cumulative exposure and did not appear to be more frequent nor more severe for patients previously treated with radiation therapy. 

In the study where paclitaxel was administered to patients with ovarian carcinoma at a dose of 135 mg/m 2/24 hours in combination with cisplatin versus the control arm of cyclophosphamide plus cisplatin, the incidences of grade IV neutropenia and of febrile neutropenia were significantly greater in the paclitaxel plus cisplatin arm than in the control arm. Grade IV neutropenia occurred in 81% on the paclitaxel plus cisplatin arm versus 58% on the cyclophosphamide plus cisplatin arm, and febrile neutropenia occurred in 15% and 4% respectively. On the paclitaxel/cisplatin arm, there were 35/1074 (3%) courses with fever in which Grade IV neutropenia was reported at some time during the course. When paclitaxel followed by cisplatin was administered to patients with advanced NSCLC in the ECOG study, the incidences of Grade IV neutropenia were 74% (paclitaxel 135 mg/m 2/24 hours followed by cisplatin) and 65% (paclitaxel 250 mg/m 2/24 hours followed by cisplatin and G-CSF) compared with 55% in patients who received cisplatin/etoposide. 

Fever was frequent (12% of all treatment courses). Infectious episodes occurred in 30% of all patients and 9% of all courses; these episodes were fatal in 1% of all patients, and included sepsis, pneumonia and peritonitis. In the Phase 3 second-line ovarian study, infectious episodes were reported in 20% and 26% of the patients treated with a dose of 135 mg/m 2or 175 mg/m 2given as a 3-hour infusion respectively. Urinary tract infections and upper respiratory tract infections were the most frequently reported infectious complications. In the immunosuppressed patient population with advanced HIV disease and poor-risk AIDS-related Kaposi's sarcoma, 61% of the patients reported at least one opportunistic infection (see CLINICAL STUDIES, AIDS-Related Kaposi's Sarcoma). The use of supportive therapy, including G-CSF, is recommended for patients who have experienced severe neutropenia (see DOSAGE AND ADMINISTRATION). 

Thrombocytopenia was reported. Twenty percent of the patients experienced a drop in their platelet count below 100,000 cells/mm 3at least once while on treatment; 7% had a platelet count <50,000 cells/mm 3at the time of their worst nadir. Bleeding episodes were reported in 4% of all courses and by 14% of all patients but most of the hemorrhagic episodes were localized and the frequency of these events was unrelated to the Paclitaxel Injection, USP dose and schedule. In the Phase 3 second-line ovarian study, bleeding episodes were reported in 10% of the patients; no patients treated with the 3-hour infusion received platelet transfusions. In the adjuvant breast carcinoma trial, the incidence of severe thrombocytopenia and platelet transfusions increased with higher doses of doxorubicin. 

Anemia (Hb <11 g/dL) was observed in 78% of all patients and was severe (Hb <8 g/dL) in 16% of the cases. No consistent relationship between dose or schedule and the frequency of anemia was observed. Among all patients with normal baseline hemoglobin, 69% became anemic on study but only 7% had severe anemia. Red cell transfusions were required in 25% of all patients and in 12% of those with normal baseline hemoglobin levels.