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

Sponsored by:	University Hospital Birmingham
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003893

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	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	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Sequencing of Chemotherapy and Radiotherapy in Adjuvant Breast Cancer

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	2250
Study Start Date:	July 1998

Detailed Description:

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.

Eligibility

Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003893

Locations

United Kingdom, England
Queen Elizabeth Hospital at University of Birmingham
Birmingham, England, United Kingdom, B15 2TH

Sponsors and Collaborators

University Hospital Birmingham

Investigators

Study Chair:

Indy Fernando, MD

University Hospital Birmingham

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Bowden SJ, Fernando IN, Burton A. Delaying radiotherapy for the delivery of adjuvant chemotherapy in the combined modality treatment of early breast cancer: is it disadvantageous and could combined treatment be the answer? Clin Oncol (R Coll Radiol). 2006 Apr;18(3):247-56. Review.

Fernando I, Bowden S, Dunn J: The combination of chemotherapy and radiotherapy in the adjuvant treatment of breast cancer. [Abstract] Radiother Oncol 58 (Suppl 1): A-34, S10, 2001.

Fernando IN. The role of radiotherapy in patients undergoing mastectomy for carcinoma of the breast. Clin Oncol (R Coll Radiol). 2000;12(3):158-65. Review.

Study ID Numbers:	CDR0000067062, CRC-TU-BR3015, EU-99005
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003893 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I breast cancer

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Folate
Cyclophosphamide
Mitomycins
Vitamin B9
Anti-Bacterial Agents
Mitomycin
Methotrexate
Analgesics
Alkylating Agents
Breast Diseases
Skin Diseases

Adjuvants, Immunologic
Breast Neoplasms
Folic Acid Antagonists
Folinic Acid
Epirubicin
Immunosuppressive Agents
Doxorubicin
Folic Acid
Fluorouracil
Mitoxantrone
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Sensory System Agents
Therapeutic Uses
Abortifacient Agents
Mitomycin
Methotrexate

Analgesics
Dermatologic Agents
Alkylating Agents
Breast Diseases
Nucleic Acid Synthesis Inhibitors
Skin Diseases
Adjuvants, Immunologic
Breast Neoplasms
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Epirubicin
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 02, 2009