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
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.
- 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
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.
- 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
- Initial stage IV disease having a complete response following platinum based therapy
- No brain metastases
- Not eligible for other high priority national or institutional study
- 18 and over
- ECOG 0-1
- Greater than 2 months
- WBC greater than 3000/mm3
- Absolute neutrophil count greater than 1500/mm3
- Platelet count greater than 100,000/mm3
- Bilirubin less than 1.5 times normal
- SGOT or SGPT less than 1.5 times normal
- PT/PTT within normal limits
- BUN less than 1.5 times normal
- Creatinine less than 1.5 times normal
- Creatinine clearance greater than 55 mL/min
- LVEF at least 45%
- 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
- No serious illness that would prevent treatment
PRIOR CONCURRENT THERAPY:
- Not specified
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- Not specified
- At least 3 weeks since prior radiotherapy
- Not specified
- No concurrent acetaminophen