A Trial of Doxorubicin/Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D for Metastatic Breast Cancer

Japan Clinical Oncology Group

Status and phase: Completed; Phase 3

Conditions: Breast Cancer; Neoplasm Metastasis

Treatments: 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 type: Interventional

Funder types: Other

Identifiers

NCT00190489

JCOG9802

C000000179

Details and patient eligibility

About

To investigate the clinical benefits of Docetaxel or alternating AC-Docetaxel in comparison with standard AC for metastatic breast cancer

Full description

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.

Sex: Female

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Hormonal therapy-resistant MBC
2. ER (-), failure of hormonal therapy for MBC, or relapse within 6 months after adjuvant hormonal therapy
3. No anthracyclines for MBC and no prior taxanes
4. At least 6 months from the completion of adjuvant chemotherapy
5. Measurable or evaluable lesions
6. Age: 20 to 75 years
7. PS: 0-3
8. WBC >= 4,000 /mm3 or ANC >=1,000 /mm3, Platelet >= 100,000 /mm3, SGOT/SGPT <= 1.5 x ULN, T-Bil <= 1.5 mg/dL, Cr <= 1.5 mg/dL
9. normal ECG
10. Written informed consent

Exclusion criteria

1. pregnant
2. malignant pleural effusion, ascites, or pericardial effusion that requires emergent treatment
3. Active infection
4. other cancer present within the last 5 years
5. previous stem cell transplantation
6. brain metastasis that requires emergent treatment
7. relapse within 6 months after completion anthracycline or during anthracycline
8. more than 250mg/m2 of anthracyclines
9. hypersensitivity of drug
10. interstitial pneumonitis or pulmonary fibrosis
11. positive HBs
12. antipsychotic medication
13. doctor's judgement

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)