Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

PRIMARY OBJECTIVES:

I. To determine the event-free survival and survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.

SECONDARY OBJECTIVES:

II. To determine the toxicity of a combination of low-dose IL-2 and GM-CSF in patients following HDC with BUMELTT and PBSC support.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive busulfan orally (PO) once every 6 hours on days -8, -7, and -6; melphalan IV over 30 minutes on days -5 and -4; and thiotepa IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell infusion on day 0.

POST-TRANSPLANT THERAPY: All patients receive tamoxifen citrate* PO once daily beginning prior to aldesleukin (IL-2) and sargramostim (GM-CSF) therapy and continuing for 5 years or until relapse (estrogen receptor [ER]- or progesterone receptor [PR]-positive patients) OR until completion of IL-2/GM-CSF therapy (ER-negative or PR-negative patients). Eligible patients receive IL-2 subcutaneously (SC) daily and GM-CSF SC 3 times weekly for 12 weeks beginning 30-100 days after transplantation. Patients may receive radiotherapy after completion of IL-2/GM-CSF treatment if no prior radiotherapy was given before transplantation.

*Stage IV patients not receiving IL-2/GM-CSF therapy who received tamoxifen citrate as part of adjuvant therapy and subsequently failed, receive oral anastrozole once daily for 5 years or until progression instead of tamoxifen.

[*For postmenopausal patients, the choice and duration of hormonal therapy given in addition to or an alternative to tamoxifen therapy will be at the physician's discretion]

Patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Inclusion criteria

• Patients with inflammatory (stage IIIb) or responsive stage IV breast cancer with metastasis to soft tissue and/or bone; responsive stage IV disease is defined as patients who achieve a PR (>= 50% reduction in measurable tumor burden) or CR following initial chemotherapy for metastatic disease or patients with locally recurrent disease (chest wall/axillary nodes) who are rendered disease-free following surgery or radiation therapy without receiving chemotherapy; bone disease is categorized as responsive if there is demonstrated sclerosis of prior lesions with no new lesions
• Patients should have received 4-7 cycles of an Adriamycin and/or taxane-based regimen for stage IIIb or stage IV disease; locally recurrent (chest wall/axillary nodes) patients rendered NED by RT or surgery do not need to receive chemotherapy for stage IV disease prior to Cytoxan/Taxol
• Patient has received Cytoxan 4 gm/m^2 x 1 and Taxol 250 mg/m^2 x 1 per FHCRC protocol 506.03; Cytoxan/Taxol must be given after all other chemotherapy is completed and before transplant
• Stem cells were collected after mobilization with Cytoxan/Taxol or after mobilization from an FHCRC approved cytokine protocol; if syngeneic collection, PBSC's were collected by using G-CSF according to FHCRC protocol 753; patient has an adequate number of peripheral blood stem cells stored (>= 2.5 x 10^6 CD34+ cells/kg)
• The patient must have the capacity to give informed consent; the patient must have signed an approved consent form conforming with federal and institutional guidelines
• Hepatic function: Bilirubin =< 2 mg%; SGOT or SGPT =< 2.5 x institutional normal
• Renal function: Creatinine =< 2.0 mg/dl or a creatinine clearance >= 50 mg/min
• Pre-Study tests have been performed as outlined in the Study Calendar
• Patients will begin IL-2/GM-CSF therapy if they meet the following criteria post-transplant:
• Can start therapy 30 to 100 days after transplant
• Karnofsky performance status > 60
• ANC > 1,000 cells/mm^3 and platelets > 30,000/cells/mm^3 (transfusion independent) for at least 5 days before starting therapy
• Total bilirubin =< 2.5 x upper limit of normal
• SGOT =< 2.5 x upper limit of normal
• Creatinine =< 2.0 mg/dl

Exclusion criteria

• Patients with a Karnofsky Performance Score less than 70
• Patients with a left ventricular ejection fraction less than 50 % (LVEF must be performed in patients with symptoms of CHF, abnormal cardiac exam or history of Adriamycin therapy total dose > 400 mg/m^2)
• Patient is pregnant
• Patient is seropositive for the human immunodeficiency virus
• Patients with a history of seizures
• Patients with hypersensitivity to E.coli preparations
• Patients with active auto-immune disease
• Patients with clinically significant pulmonary disease, i.e., diffusion capacity corrected < 60% of predicted; patients with pulmonary problems should be evaluated with appropriate pulmonary studies and/or consult
• Patients with a history of CNS lesion (brain or carcinoid meningitis)
• Patients with significant active infection precluding transplant
• Patients who have had more than one prior chemotherapy regimen for stage IV disease or a prior transplant for any stage disease
• Patients who have had CD34+ selection of their PBSC products
• Patients will not receive IL-2/GM-CSF therapy if they:
• Are > 100 days from transplant
• Have documented disease progression after transplant
• Have an active infection
• Manifested cardiac complications during the initial transplant period, including arrhythmias (that required therapy), congestive heart failure, angina, myocardial infarct, or decreased LVEF to < 45%
• Currently have pericardial effusions, pleural effusions or ascites
• Manifested pulmonary toxicity during the initial transplant period and have a diffusion capacity corrected =< 60%
• Are on steroids
• Currently have a Grade 3 toxicity from BuMelTT
• If the patient does not wish to receive the therapy