Adjuvant Chemotherapy Plus Radiation Therapy in Treating Women With Early-Stage Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumors cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy is more effective for early-stage breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of adjuvant chemotherapy plus radiation therapy in treating women who have early-stage breast cancer.

Detailed Description
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OBJECTIVES: Compare the effects of synchronous vs sequential adjuvant chemotherapy and radiotherapy on local recurrence, disease-free and overall survival, and treatment delay in women with early-stage breast cancer. Compare the safety of these regimens, in terms of dose intensity and toxicity, in this patient population. Compare the quality of life and cosmetic outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical oncologist, axillary clearance (yes vs no), radiotherapy boost intent (boost vs no boost), and chemotherapy intent (cyclophosphamide, methotrexate, and fluorouracil [5-FU] vs anthracycline-containing regimen). Patients are randomized to one of two treatment arms. Patients receive any chemotherapy regimen that includes cyclophosphamide, methotrexate, and 5-FU. Some regimens may also include epirubicin, doxorubicin, mitoxantrone, and/or mitomycin. Chemotherapy repeats every 3 weeks for 4-8 courses. Arm I (synchronous chemoradiotherapy): Patients receiving synchronous therapy receive any of the above chemotherapy regimens plus daily radiotherapy between courses 2 and 3 OR courses 5 and 6 of chemotherapy. Radiotherapy is administered for 3-5 weeks. Arm II (sequential chemoradiotherapy): Patients receiving sequential therapy receive any of the above chemotherapy regimens followed by daily radiotherapy beginning after completion of all chemotherapy (after course 6 or 8). Radiotherapy is administered for 3-5 weeks. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed before chemotherapy, 2-3 weeks after the completion of all treatment, and then at 1, 2, and 5 years. Patients are followed annually for 10 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 2,250 patients (1,125 per treatment arm) will be accrued for this study.

Official Title
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Sequencing of Chemotherapy and Radiotherapy in Adjuvant Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: CMF regimen
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: epirubicin hydrochloride
* Drug: fluorouracil
* Drug: methotrexate
* Drug: mitomycin C
* Drug: mitoxantrone hydrochloride
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast cancer Early-stage disease No metastatic disease Complete surgical excision of tumor Planned use of adjuvant chemotherapy and radiotherapy If participating in the cosmetic outcome evaluation portion of the study, must have unilateral disease Hormone receptor status Not specified PATIENT CHARACTERISTICS: Age: Not specified Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: Bone marrow function adequate Hepatic: Hepatic function adequate Renal: Renal function adequate Cardiovascular: Cardiac function adequate Other: No other prior malignancy except basal cell or squamous cell skin cancer or carcinoma in situ No other medical or social condition that would preclude study compliance Fit to receive both adjuvant chemotherapy and radiotherapy (administered either synchronously or sequentially) Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No prior chemotherapy No concurrent epirubicin and doxorubicin as a study combination chemotherapy regimen Endocrine therapy: Prior or concurrent hormonal therapy allowed No concurrent tamoxifen if treated with methotrexate, mitomycin, and mitoxantrone as a study combination chemotherapy regimen Radiotherapy: See Disease Characteristics No concurrent internal mammary chain irradiation No concurrent orthovoltage irradiation to the whole breast Surgery: See Disease Characteristics Recovered from prior surgery Other: Concurrent participation in another clinical trial allowed
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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: CMF regimen|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: epirubicin hydrochloride|nan|
|Drug: fluorouracil|nan|
|Drug: methotrexate|nan|
|Drug: mitomycin C|nan|
|Drug: mitoxantrone hydrochloride|nan|
|Procedure: adjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer