Combination Chemotherapy, Bone Marrow Transplantation, and Peripheral Stem Cell Transplantation in Treating Patients With Ovarian Epithelial Cancer

OBJECTIVES: I. Determine the maximum tolerated dose of carboplatin when combined with
cyclophosphamide as high-dose therapy followed by autologous bone marrow and peripheral blood
stem cell rescue in patients with platinum sensitive ovarian epithelial carcinoma. II.
Determine the efficacy of this regimen in these patients.

OUTLINE: This is a dose escalation study of carboplatin. Autologous bone marrow (ABM) is
harvested on day -11, filgrastim (G-CSF) is administered subcutaneously (SC) on days -11 to
-7, and autologous peripheral blood stem cells (PBSC) are harvested on day -6. Patients
receive high dose chemotherapy comprising carboplatin IV over 15 minutes on days -5 and -4
and cyclophosphamide IV over 1 hour on days -3 and -2. PBSC are reinfused on day -1, ABM is
reinfused on day 0, and G-CSF is administered SC beginning on day 7 and continuing until
blood counts recover. Cohorts of 2-4 patients receive escalating doses of carboplatin until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no
more than 10% of patients experience dose-limiting toxicity. A minimum of 6 patients receive
carboplatin at the MTD. Patients are followed at 1 month and then every 3 months for 5 years.

PROJECTED ACCRUAL: A minimum of 18 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS: Histologically confirmed advanced ovarian epithelial malignancy of
one of the following histologies: Serous adenocarcinoma Endometrioid adenocarcinoma
Mucinous adenocarcinoma Undifferentiated carcinoma Clear cell adenocarcinoma Mixed
epithelial carcinoma Fallopian tube and extraovarian peritoneal papillary serous tumors
also allowed Documented responsiveness (using established clinical criteria) to a
platinum-based chemotherapy regimen required Partial or complete clinical response to the
most recent chemotherapy regimen required Bone marrow aspirate and biopsy morphologically
negative for carcinoma and cellularity greater than 50% No CNS involvement

PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: GOG 0-2 Life expectancy: Not
specified Hematopoietic: WBC greater than 3,000/mm3 Absolute neutrophil count at least
1,500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL*
SGOT less than 60 IU/mL* * Unless abnormality due to metastatic involvement Renal:
Creatinine less than 2.0 mg/dL* * Unless abnormality due to metastatic involvement
Cardiovascular: LVEF at least 45% by MUGA scan No active congestive heart failure No
myocardial infarction within the past year No active arrhythmia No active angina pectoris
No uncontrolled hypertension Pulmonary: FVC and FEV at least 50% predicted Other: No
peripheral neuropathy No uncontrolled diabetes mellitus No history of other malignancy
except basal cell or squamous cell skin cancer No debilitating medical or psychiatric
illness that would preclude informed consent or study

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease
Characteristics No more than 2 prior chemotherapy regimens At least 4 weeks since prior
chemotherapy (at least 6 weeks since prior nitrosoureas) Endocrine therapy: Not specified
Radiotherapy: No prior radiotherapy for ovarian cancer Surgery: Not specified