Topotecan in Treating Patients With Gynecologic Cancer That Cannot Be Removed by Surgery

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of topotecan in treating patients with gynecologic cancer that cannot be removed by surgery.

OBJECTIVES:

Primary

* To establish the maximum tolerated dose (MTD) of oral topotecan hydrochloride in patients with unresectable gynecologic malignancies.
* To determine the safety and tolerability of this drug in these patients.
* To obtain pharmacokinetic data to assess plasma concentrations of this drug when administered at the MTD.

Secondary

* To explore the response in patients treated with this drug.

OUTLINE: Patients receive oral topotecan hydrochloride on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients treated at the maximum tolerated dose undergo blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically\* or cytologically confirmed unresectable gynecologic malignancy for which standard curative or palliative care is not available

  * All tumor types allowed NOTE: \*Histologic confirmation of recurrence is not required
* Measurable or nonmeasurable disease

  * If CT scan was used to evaluate measurable disease, lesions must be clearly defined and be ≥ 10 mm on spiral CT scan
* No "borderline tumors" or tumors with low malignant potential

PATIENT CHARACTERISTICS:

* Karnofsky performance status 60-100%
* Life expectancy ≥ 12 weeks
* ANC ≥ 1,500/μL
* Platelet count ≥ 100,000/μL
* Hemoglobin ≥ 9 g/dL
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Creatinine clearance ≥ 60 mL/min
* AST/ALT ≤ 2.5 times ULN (\< 5 times ULN if liver metastases are present)
* Alkaline phosphatase ≤ 2.5 times ULN (\< 5 times ULN if liver metastases are present)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Adequate intestinal function (i.e., no gastrostomy tube or requirement for IV hydration or nutritional support)
* No severe gastrointestinal bleeding or intestinal obstruction
* No other condition that would affect gastrointestinal absorption and motility
* No septicemia, severe infection, or acute hepatitis
* No other malignancies requiring chemotherapy or radiotherapy within the past 5 years, except skin cancer
* No concurrent severe medical problem unrelated to the malignancy that would significantly limit full compliance with the study, expose the patient to extreme risk, or decrease life expectancy

PRIOR CONCURRENT THERAPY:

* At least 28 days since prior investigational drugs (including cytotoxic drugs)
* At least 4 weeks since prior chemotherapy, radiotherapy, biologic therapy, or surgery and recovered
* No more than 3 prior chemotherapy regimens
* No prior topotecan hydrochloride or other camptothecin analogs
* No prior radiotherapy to \> 25% of the bone marrow
* No other concurrent chemotherapy, radiotherapy, biologic therapy, immunotherapy, or hormonal therapy for cancer
* No concurrent administration of any of the following:

  * P-glycoprotein (ABCB1, Pgp, MDR1) inhibitors or inducers
  * Breast cancer-resistant protein (ABCG2, BCRP, MXR) inhibitors or inducers
* No concurrent chronic H2 antagonists, proton pump inhibitors, or antacids for gastritis, gastroesophageal reflux disease, or gastric or duodenal ulcers

  * Intermittent antacid therapy is allowed provided it is given ≥ 6 hours prior to and ≥ 90 minutes after study drug administration