Adjuvant High-Dose, Sequential Chemotherapy in Treating Patients With Resected Breast Cancer

Sequential Adjuvant Chemotherapy With Doxorubicin, Taxol, and Cyclophosphamide for Stage II or III Resectable Breast Cancer With Four or More Involved Axillary Lymph Nodes

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose sequential chemotherapy as adjuvant therapy in treating patients with stage II or stage III breast cancer who have four or more positive axillary lymph nodes.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Radiation: radiation therapy; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Biological: filgrastim; Drug: tamoxifen citrate

Detailed Description

OBJECTIVES: I. Evaluate the efficacy of dose intensive, sequential adjuvant chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide in patients with stage II/III resected breast cancer. II. Evaluate the toxicity of this regimen in these patients.

OUTLINE: All patients receive sequential chemotherapy regimens consisting of 3 courses each of doxorubicin, paclitaxel, and cyclophosphamide on a schedule of one course every 14 days. Following completion of chemotherapy, patients who underwent breast conservation surgery receive radiotherapy. Mastectomy patients with 10 or more positive nodes or with T3-4 tumors are also eligible for delayed radiotherapy. Patients who are hormone receptor positive (or whose receptor status is unknown) are treated with oral tamoxifen for 5 years, beginning after completion of all other therapy. Patients are followed every 3 months for 2 years, every 6 months for 3 years, then yearly.

PROJECTED ACCRUAL: At total of 90 patients will be entered.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast with involvement of 4 or more axillary nodes, including any T N1 M0 Concurrent bilateral breast cancer allowed Complete resection required Total mastectomy or breast conserving surgery Adjuvant radiotherapy planned after protocol chemotherapy Clear surgical margins Axillary dissection yielding at least 9 lymph nodes Entry required within 8 weeks of definitive surgery Hormone receptor status: Any status

PATIENT CHARACTERISTICS: Age: Over 18 Sex: Not specified Menopausal status: Not specified Performance status: Karnofsky 80%-100% ECOG 0 or 1 Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no greater than 1.5 times normal AST no greater than 2 times normal Alkaline phosphatase no greater than 2 times normal Renal: Creatinine no greater than 1.8 mg/dL OR Creatinine clearance at least 60 mL/min Urinalysis normal Cardiovascular: Left ventricular ejection fraction normal on MUGA or echocardiogram No congestive heart failure requiring medical therapy No serious arrhythmia No first-, second-, or third-degree heart block Other: No abnormal CT of chest or abdomen No uncontrolled infection No serious medical condition that would prevent treatment No second malignancy except curatively treated: Nonmelanomatous skin cancer Carcinoma in situ of the cervix Not pregnant Negative pregnancy test Barrier contraception required of fertile patients before, during, and for 6 months after protocol therapy

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy Endocrine Therapy: No concurrent hormonal therapy unless unrelated to cancer Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics Other: No concurrent medication affecting conduction unless cleared by a cardiologist, e.g.: Beta blockers Digoxin Antiarrhythmia agents Calcium channel blockers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Study Chair: Maysa Abu-Khalaf, MD, Yale University

Study record dates

Study Major Dates

• Study Start: February 1, 1994
• Primary Completion (Actual): January 1, 2002
• Study Completion (Actual): January 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: February 5, 2004
• First Posted (Estimate): February 6, 2004

Study Record Updates

• Last Update Posted (Estimate): August 26, 2009
• Last Update Submitted That Met QC Criteria: August 24, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; male breast cancer; stage II breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Cyclophosphamide; Paclitaxel; Doxorubicin; Liposomal doxorubicin; Tamoxifen
• Other Study ID Numbers: CDR0000064337; YALE-HIC-7374; NCI-V95-0720

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No