Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Persistent Epithelial Ovarian Cancer, Fallopian Tube, or Primary Peritoneal Cancer

Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Persistent Epithelial Ovarian Cancer, Fallopian Tube, or Primary Peritoneal Cancer

Phase I-II Study of Tandem Cycles of High Dose Chemotherapy Followed by Autologous Hematopoietic Stem Cell Support in Women With Persistent, Refractory or Recurrent Advanced (Stage III or IV), Epithelial Ovarian Cancer

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 and kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy and autologous peripheral stem cell transplantation in treating patients with recurrent or persistent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer.

OBJECTIVES: Determine the maximum tolerated dose of topotecan with a fixed dose of etoposide phosphate as a component of a multicourse high dose chemotherapy regimen supported by peripheral blood stem cell transplantation in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer. Evaluate the response, time to progression, disease free survival, and overall survival in this patient population. OUTLINE: This is a dose escalation study of topotecan. All patients receive induction therapy consisting of 1 to 2 courses of mobilization therapy. Subcutaneous filgrastim (G-CSF) is given beginning 24 hours after induction dose. Following induction therapy, peripheral blood stem cells (PBSC) are harvested. After patients receive high dose paclitaxel and carboplatin chemotherapy, a portion of the PBSC are reinfused. When patients recover from the paclitaxel/carboplatin chemotherapy the administration of topotecan and etoposide phosphate begins. Topotecan is administered, as a 72 hour continuous infusion, according to a dose escalation schedule with a fixed dose of etoposide phosphate. A second portion of PBSC are reinfused after topotecan/etoposide phosphate chemotherapy. A course of thiotepa is given along with the final portion of PBSC after treatment with topotecan and etoposide phosphate. Dose escalation of topotecan continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year and every 4 months thereafter to determine progression free and overall survival. PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for the phase I portion of this study, and 25 more patients will be accrued for the phase II portion.

DISEASE CHARACTERISTICS: Histologically proven persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer following at least 3 courses of initial standard platinum based chemotherapy OR have radiologic evidence of recurrence with a CA125 greater than 100 Initial stage IV disease having a complete response following platinum based therapy allowed No brain metastases Not eligible for other high priority national or institutional study PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Greater than 2 months Hematopoietic: WBC greater than 3000/mm3 Absolute neutrophil count greater than 1500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 1.5 times normal SGOT or SGPT less than 1.5 times normal PT/PTT within normal limits Renal: BUN less than 1.5 times normal Creatinine less than 1.5 times normal Creatinine clearance greater than 55 mL/min Cardiovascular: LVEF at least 45% Other: Not pregnant or nursing HIV negative No prior malignancy other than curatively treated carcinoma in situ of the cervix, nonmelanoma skin cancer, or breast cancer if the risk of recurrence is sufficiently low No serious illness that would prevent treatment PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy Surgery: Not specified Other: No concurrent acetaminophen