Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Mitoxantrone Compared With Combination Chemotherapy in Treating Women With Good-Risk Metastatic Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 35 to 80 GER-AIO-02/92 EU-93010

Objectives

I.  Compare survival and quality-of-life scores (composed of time to 
progression, WHO performance status, subjective patient evaluation, and 
subjective adverse event profile) among women with metastatic breast cancer of 
favorable prognosis randomized to mitoxantrone vs. 
cyclophosphamide/methotrexate/fluorouracil (CMF) as first-line chemotherapy 
for metastatic disease.

II.  Compare remission rate, time to remission, remission duration, time to 
best response, objective adverse events, and patient acceptance of treatment 
on these 2 regimens.

III.  Investigate which prognostic subgroups of patients benefit from 
treatment.

Entry Criteria

Disease Characteristics:

Histologically documented metastatic breast cancer of good prognosis, defined
as either of the following sets of characteristics:
  I.  Age over 35
      No hepatic metastases
      No pulmonary metastases

  II. Age over 35
      Pulmonary metastases but no hepatic metastases or other disease
        manifestations
      Disease-free interval of greater than 18 months

Indication for chemotherapy documented by either:
  Hormone receptor negativity OR
  Hormone-resistant disease

Measurable metastatic disease required
  Nonmeasurable disease includes:
     Pleural effusions
     Metastases verified only histologically
     Tumor parameters not precisely measurable (e.g., bone marrow involvement,
        lymphangitic disease)

No CNS metastasis or bone marrow carcinomatosis

Prior/Concurrent Therapy:

Biologic therapy:
  No concurrent biologic therapy

Chemotherapy:
  No prior chemotherapy for metastatic disease
  No adjuvant chemotherapy within 12 months
     No prior anthracycline or anthraquinone

Endocrine therapy:
  Hormone-resistant disease required of receptor-positive patients
  No concurrent endocrine therapy

Radiotherapy:
  No prior mediastinal irradiation
     Adjuvant irradiation of parasternal nodes eligible
  No prior irradiation to more than 25% of bone marrow
  No concurrent irradiation of sole measurable lesion

Surgery:
  Not specified

Patient Characteristics:

Age:
  35-80

Sex:
  Women only

Menopausal status:
  Pre- and postmenopausal

Performance status:
  WHO 0-2

Life expectancy:
  At least 3 months

Hematopoietic:
  WBC greater than 4,000
  AGC greater than 2,000
  Platelets greater than 100,000

Hepatic:
  Bilirubin not greater than 5 mg/dL
  Alkaline phosphatase not greater than 240 U/L

Renal:
  Creatinine not greater than 2 mg/dL

Cardiovascular:
  No uncontrolled hypertension
  No congestive heart failure within 6 months
  No myocardial infarction within 6 months
  
Other:
  No requirement for anticoagulant therapy
     Thrombosis developing on protocol will be treated and not be cause for
     removal
  No acute or chronic infection
  No second primary tumor
  No other serious illness
  Effective contraception required

Expected Enrollment

A total of 296 patients will be required.

Outline

This is a randomized study.  Patients are stratified by age, disease-free 
interval, prior adjuvant chemotherapy, and participating institution.

Patients in the first group receive mitoxantrone every 4 weeks.

Patients in the second group receive fluorouracil, epirubicin, and 
cyclophosphamide (FEC) on days 1 and 8 (oral cyclophosphamide on days 1-14 may 
be substituted for intravenous cyclophosphamide) every 4 weeks for at least 2 
courses.

Patients aged 70 or over begin therapy at reduced doses and increase to full 
dose by the third course if treatment is well tolerated.

Patients who achieve a complete response (CR) receive 2 additional courses as 
consolidation therapy; patients who relapse after a CR are re-treated with the 
original regimen.  Upon second relapse, patients are crossed to the opposite 
arm.

Patients who achieve less than a CR on the initial or second induction 
continue assigned treatment until disease progression, at which time they 
cross to the other arm, or for a maximum of 12 courses.  Third-line therapy is 
at the discretion of the physician.

Patients are evaluated just prior to the third scheduled course and every 12 
weeks thereafter.

Trial Contact Information

Trial Lead Organizations

Arbeitsgemeinschaft fur Internistische Onkologie

Else Heidemann, MD, Protocol chair		Ph: 49-711-991-3501