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

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Breast Cancer, Neoplasm Metastasis

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hormonal therapy-resistant MBC ER (-), failure of hormonal therapy for MBC, or relapse within 6 months after adjuvant hormonal therapy No anthracyclines for MBC and no prior taxanes At least 6 months from the completion of adjuvant chemotherapy Measurable or evaluable lesions Age: 20 to 75 years PS: 0-3 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 normal ECG Written informed consent Exclusion Criteria: pregnant malignant pleural effusion, ascites, or pericardial effusion that requires emergent treatment Active infection other cancer present within the last 5 years previous stem cell transplantation brain metastasis that requires emergent treatment relapse within 6 months after completion anthracycline or during anthracycline more than 250mg/m2 of anthracyclines hypersensitivity of drug interstitial pneumonitis or pulmonary fibrosis positive HBs antipsychotic medication doctor's judgement

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AC (ADM 40mg/m2+CPA 500mg/m2) q21 days x 6 cycles|nan|
|Drug: Docetaxel 60mg/m2 every 21 days for 6 cycles|nan|
|Drug: AC and Docetaxel 60mg/m2 alternately q21 days for 6 cycles|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to treatment failure |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  |  | 
| progression-free survival |  |  | 
| response rate |  |  | 
| adverse events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic breast cancer, drug therapy, doxorubicin, docetaxel