Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Completed no age specified NCI SWOG-8203/04 SWOG-8204

Objectives

I.  Determine the comparative response rate, duration of response, and 
survival of equimyelosuppressive doses of adriamycin, mitoxantrone, and 
bisantrene as single agents in breast cancer patients, not previously exposed 
to an intercalating agent, using a single-dose, every-three-week schedule.
II.  Determine the salvage response rate of adriamycin, mitoxantrone, or 
bisantrene in breast cancer patients failing one of these three agents.
III.  Assess the cardiotoxicity of adriamycin, mitoxantrone, and bisantrene as 
determined by history, physical examination, and measurement of the left 
ventricular ejection fraction.
IV.  Compare the relative noncardiac toxicities of the three agents.
V.  Prospectively evaluate the in vitro effects of these drugs in the cloning 
assay, and correlate them with in vivo activity in those patients with 
biopsiable disease.  Per April 1983 revision, this objective has been removed.
VI.  Measure the peak plasma levels of each drug, and correlate the levels 
with response and toxicity.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients with pathologically verified 
breast cancer.  There must be objectively measurable or evaluable disease 
(excluding CNS metastases); estrogen receptor data on the primary or 
metastatic tumor are desirable but not required.  Patients must have a 
performance status of 2 or better (Karnofsky 50-60) and adequate hematologic 
(unless bone marrow is compromised by tumor involvement), renal, and hepatic 
function.  Patients must have received only one prior chemotherapy regimen, 
which may have included cyclophosphamide or L-phenylalanine mustard, 
methotrexate, 5-fluorouracil, vincristine, prednisone, or tamoxifen; a 
CMF-like regimen given as an adjuvant therapy and then given again as initial 
therapy for advanced disease will be considered as one drug regimen.  Prior 
treatment with any of the protocol agents or radiation to more than 10% of the 
bone marrow is not allowed.  Estrogen-receptor-positive patients must have 
failed endocrine therapy unless they have lymphangitic lung metastases or 
advanced liver involvement.  Concurrent palliative radiation therapy to 
non-indicator lesions and glucocorticoids for brain metastases are allowed.  
Patients with a history of congestive heart failure, myocardial infarction 
within the past 6 months, or severe angina pectoris are not eligible.

Expected Enrollment

122 patients per arm will be required.

Outline

Randomized study.
Arm I:  Single-agent Chemotherapy.  Adriamycin, ADR, NSC-123127.
Arm II:  Single-agent Chemotherapy.  Mitoxantrone, Dihydroxyanthracenedione, 
DHAD, NSC-301739.
Arm III:  Single-agent Chemotherapy.  Bisantrene, Anthracenedicarboxaldehyde, 
ADC, NSC-337766.

Cowan JD, Neidhart J, McClure S, et al.: Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst 83 (15): 1077-84, 1991.[PUBMED Abstract]

Cowan JD, Osborne CK, Neidhart JA, et al.: A randomized trial of doxorubicin, mitoxantrone and bisantrene in advanced breast cancer (a South West Oncology Group Study). Invest New Drugs 3 (2): 149-52, 1985.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Glenn Mills, MD, Protocol chair		Ph: 318-813-1440 Email: gmills@lsuhsc.edu