RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining chemotherapy with peripheral stem cell
transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill
more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of melphalan and thiotepa followed by
peripheral stem cell transplantation in treating patients with stage III or stage IV
epithelial ovarian cancer in complete remission.
OBJECTIVES: I. Assess the toxic effects of combined high dose melphalan and thiotepa
chemotherapy followed by stem cell rescue in patients with stage III or IV ovarian
epithelial cancer in complete remission. II. Determine the maximum tolerated dose of
thiotepa that can be given with melphalan in these patients. III. Evaluate the interpatient
blood level variability and pharmacokinetics of melphalan given intravenously.
OUTLINE: This is a dose escalation study of thiotepa. Patients receive cytoreduction and
mobilization of peripheral blood stem cells (PBSC) with filgrastim (G-CSF) and
cyclophosphamide/paclitaxel, cyclophosphamide/etoposide or
cyclophosphamide/etoposide/cisplatin within 30-90 days of last dose of standard therapy.
PBSC are then collected. Patients then receive melphalan IV over 30 minutes on days -6 and
-5 and thiotepa IV over 2 hours on days -4 and -3. PBSC are reinfused on day 0. G-CSF is
administered on days 0-21. Cohorts of 5-15 patients each receive escalating doses of
thiotepa until the maximum tolerated dose (MTD) is reached. The MTD is determined as the
dose at which 2-5 of 4-15 patients experience dose limiting toxicity. Patients are followed
at 100 days, then at 6, 12, and 24 months.
PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study over 2 years.
DISEASE CHARACTERISTICS: Histologically confirmed stage III/IV ovarian epithelial cancer
in first or second clinical complete remission after receiving a minimum of 4-10 courses
of chemotherapy consisting of paclitaxel and either cisplatin or carboplatin Ovarian
epithelial cancer of following histologic types: Serous adenocarcinoma Mucinous
adenocarcinoma Clear cell adenocarcinoma Transitional cell Adenocarcinoma N.O.S.
Endometrioid adenocarcinoma Undifferentiated carcinoma Mixed epithelial carcinoma
Malignant Brenner's Tumor Remission stability maintained for at least 4 weeks Protocol
therapy must begin 30-90 days after last dose of standard therapy No active pleural or
pericardial effusion No prior/concurrent brain metastasis or carcinoid meningitis
PATIENT CHARACTERISTICS: Age: 18 to 60 Performance status: Karnofsky 70-100% Life
expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 1.5
times the upper limit of normal (ULN) SGOT or SGPT less than 2.0 times ULN Albumin greater
than 2.0 g/dL Renal: Creatinine clearance greater than 60 mL/min Cardiovascular: Ejection
fraction greater than 45% by MUGA Pulmonary: If history of smoking or abnormal lung
function, Diffusion capacity greater than 50% (corrected) A-a gradient less than 20 Other:
No history of hemorrhagic cystitis No second malignancy within the last 5 years except
basal cell skin cancer HIV negative No chronic active hepatitis B No hepatitis C No
history of Aspergillus infection
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior stem cell transplant Chemotherapy:
Prior chemotherapy consisting of paclitaxel and either cisplatin or carboplatin Endocrine
therapy: Not specified Radiotherapy: No prior radiation therapy for malignancy (excluding
chest wall radiation therapy for breast cancer) Surgery: Not specified