A Trial of Doxorubicin/Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D for Metastatic Breast Cancer
Drug: AC (ADM 40mg/m2+CPA 500mg/m2) q21 days x 6 cycles
Drug: Docetaxel 60mg/m2 every 21 days for 6 cycles
Drug: AC and Docetaxel 60mg/m2 alternately q21 days for 6 cycles
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase III Trial of Doxorubicin /Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D (AC-D) as Front-line Chemotherapy for Metastatic Breast Cancer: Japan Clinical Oncology Group Trial (JCOG9802)|
- time to treatment failure
- overall survival
- progression-free survival
- response rate
- adverse events
|Study Start Date:||January 1999|
|Study Completion Date:||May 2006|
|Primary Completion Date:||May 2006 (Final data collection date for primary outcome measure)|
power to detect a 50% increase in median TTF at 0.025 one-sided alpha in AC vs. D and AC vs. AC-D.
Results: 441pts (146 in AC, 147 in D, 148 in AC-D) were randomized between 01/99 and 05/03. Major grade 3-4 toxicities were neutropenia (26/45/46% for AC/D/AC-D), febrile neutropenia (3/4/6%), nausea/vomiting (3/3/4%). There was no toxic death. One grade 4 diarrhea in AC-D and 1 secondary leukemia (APL) in D were reported. Response (CR/PR) rates were 30, 41, and 35% for AC, D, and AC-D respectively. Median TTF (AC, D, and AC-D) are 6.4, 6.4, and 6.7 months (p =.255 for AC vs. D, p =.275 for AC vs. AC-D), and median overall survival are 22.4, 25.7, and 25.0 months (p=.092 for AC vs. D, p=.076 for AC vs. AC-D). The same difference was shown by the adjusted Cox model.
Conclusions: No benefit was demonstrated in D and AC-D over AC in TTF, however, D and AC-D tended to be superior to AC in response rate and overall survival. Survival benefit of front-line docetaxel should be re-evaluated by further long follow-up.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00190489
|National Cancer Center Hospital|
|Chuo-ku, Tsukiji, 5-1-1, Tokyo, Japan, 104-0045|
|Study Chair:||Shigemitsu Takashima, MD, PhD||National Shikoku Cancer Center|