Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy

Yoshimasa Kosaka, Yoshiaki Rai, Norikazu Masuda, Toshimi Takano, Toshiaki Saeki, Seigo Nakamura, Ryutaro Shimazaki, Yoshinori Ito, Yutaka Tokuda, Kazuo Tamura, Yoshimasa Kosaka, Yoshiaki Rai, Norikazu Masuda, Toshimi Takano, Toshiaki Saeki, Seigo Nakamura, Ryutaro Shimazaki, Yoshinori Ito, Yutaka Tokuda, Kazuo Tamura

Abstract

Purpose: Pegfilgrastim is a pegylated form of filgrastim, a recombinant protein of granulocyte colony-stimulating factor, that is used to reduce the risk of febrile neutropenia (FN). Here, we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide (TC) chemotherapy.

Methods: We conducted a double-blind, placebo-controlled, randomized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients. A total of 351 women (177 in the pegfilgrastim group and 174 in the placebo group) between 20 and 69 years of age with stage I-III invasive breast carcinoma who were to receive TC chemotherapy (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks) as either neoadjuvant or adjuvant therapy were enrolled; 346 of these patients were treated with either pegfilgrastim (n = 173) or placebo (n = 173).

Results: The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group (1.2 vs. 68.8 %, respectively; P < 0.001). In addition, patients in the pegfilgrastim group required less hospitalization and antibiotics for FN. Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy.

Conclusions: Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients.

Figures

Fig. 1
Fig. 1
Patient allocation and disposition. FAS full analysis set
Fig. 2
Fig. 2
Changes in absolute neutrophil counts during the first cycle of chemotherapy for patients in the full analysis set. Data points and error bars indicate the mean and standard deviation of 173 measurements, respectively. The horizontal dashed line marks an absolute neutrophil count (ANC) of 500/μL. Open circles denote values for the placebo group, whereas closed circles denote values for the pegfilgrastim group

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