Breast Cancer, Neutropenia, Febrile Neutropenia
Conditions
Keywords
Breast cancer, Adjuvant, Docetaxel, Adriamycin, Cyclophosphamide, Neutropenia, Filgrastim, Pegfilgrastim
Brief summary
To compare the efficacy and safety of Day 2 (D2) once a cycle pegfilgrastim with Intermittent Every Other Days of 5 Shot (D3-11) filgrastim in early breast cancer patients treated with adjuvant Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) regimen
Detailed description
According to manufacturers' recommendations (Amgen: Neupogenᵀᴹ), filgrastim are to start 24 hrs after the last dose of chemotherapy and continue until absolute neutrophil count (ANC) has recovered to within the normal range (or for 14 days). However, for economic and practical reasons and/or patient's convenience, it has been common practice to initiate filgrastim at a later days of cycle and/or administer a shorter course of treatment. Data from several clinical studies have shown that 10-11 days' filgrastim treatment is required for optimal prophylaxis for febrile neutropenia (FN), and data from other cancers shows that suboptimal use of G-CSFs could deteriorate clinical outcomes. However, in two recent randomized study with breast cancer patients undergoing TAC chemotherapy, acceptable incidence (7-18%) of FN was shown with the consecutive 6 or 7-daily filgrastim schemes. Also, although there is theoretical concern that there can be wide fluctuations in the patient's ANC over time in alternate or intermittent filgrastim administration, because there was no difference in clinical outcomes between daily- or intermittent-dose filgrastim schedules in previous literatures, the intermittent every other day of 5 shot-filgrastim scheme would have clinical outcomes comparable with previous consecutive 6 or 7-daily filgrastim schemes in coverage of ANC nadir. Therefore, it can be justified to investigate the non-inferiority of intermittent every other days of 5 shot-filgrastim scheme compared with control arm using of pegfilgrastim on D2.
Interventions
DRUGFilgrastim
Filgrastim (Gracinᵀᴹ) is administered at the D3, D5, D7, D9, and D11 of each cycle. A dose of 5 μg/kg/day filgrastim is administered S.C. either as a bolus injection or as a continuous injection. Administer into the outer upper arm, abdomen (except within 2 inches of navel), front middle thigh, or the upper outer buttocks area.
DRUGPeg-filgrastim
Pegfilgrastim (Neulastaᵀᴹ) is administered at the D2 of each cycle. A dose of 6mg once a cycle is administered S.C., 24 (± 2) hours after completion of chemotherapy.
Sponsors
Kyowa Kirin Co., Ltd.
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
19 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The patients who underwent surgery for pathologically diagnosed early breast cancer (high risk stage II or stage III) or completely resected stage IV, and anticipated to undergo adjuvant chemotherapy with TAC regimen (docetaxel, doxorubicin, and cyclophosphamide) * The patients satisfying laboratory findings below before the enrollment of clinical trials: A. Absolute Neutrophil Count(ANC) ≥ 1,500/mm³; B. Platelet Count ≥ 100,000/mm³; C. Adequate renal functions (Cr \< 1.5 X ULN); and D. Adequate liver function (Bilirubin \< 1.5 X ULN, AST/ALT \< 2.5 X ULN) * ECOG Performance status: 0-1 * Cardiac ejection fraction ≥ 50% as measured by MUGA or 2D echocardiography without clinically significant abnormalities * Voluntarily participated in this study, and written informed consent of the patient
Exclusion criteria
* Past history of immunotherapy or chemotherapy * Past history of autologous stem cell transplantation or bone marrow transplantation * The patient undergone radiation therapy within 4 weeks after written informed consent * Patient with any other concurrent malignancies or who are currently cured with past history within 5 years (excluding completely resected stage I early skin cancer) * Pregnant or lactating women, women of childbearing potential not employing adequate contraception * Other serious illness or medical conditions inadequate to chemotherapy: A. Unstable cardiac disease (i.e. congestive heart failure, arrhythmia, symptomatic coronary artery disease) despite treatment, myocardial infarction within 6 months prior to study entry; B. History of significant neurological or psychiatric disorders including dementia or seizures; Active uncontrolled infection (viral, bacterial or fungal infection); and D. Other serious medical illnesses * Known hypersensitivity to any of the study drugs or its ingredients * Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy. * Past history of usage of granulocyte-colony stimulating factors * Patients with a known history of HIV (+) or HCV (+). However, HBV(+) patients who undergo primary prophylaxis are eligible. * Other serious illness or medical conditions determined by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of febrile neutropenia | through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks | Measured at the completion of cycle 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of anti-microbial use | through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks | Measured at the completion of cycle 3 |
| Duration of anti-microbial use | through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks | Measured at the completion of cycle 3 |
| Incidence of febrile neutropenia at each cycle | At each cycle 1, 2, and 3 (each cycle is 21 days) | Measured at the completion of each cycle 1, 2, and 3 |
| Delay rate of next chemotherapy cycle due to inadequate neutrophil recovery | At each cycle 1, 2, and 3 (each cycle is 21 days) | Measured at the completion of each cycle 1, 2, and 3 |
| Duration of delay of next chemotherapy cycle due to inadequate neutrophil recovery | At each cycle 1, 2, and 3 (each cycle is 21 days) | Measured at the completion of each cycle 1, 2, and 3 |
| Cumulative dose of chemotherapeutic agents | through the completion of cycle 1-3 (each cycle is 21 days), an average of 9 weeks | Measured at the completion of cycle 3 |
Countries
South Korea
Outcome results
None listed