Capecitabine in Treating Patients With Persistent or Recurrent Cervical Cancer

PRIMARY OBJECTIVES:

I. Determine the antitumor activity of capecitabine in patients with persistent or recurrent
non-squamous cell carcinoma of the cervix who have failed higher priority treatment
protocols.

II. Determine the nature and degree of toxicity of this drug in these patients. III.
Determine whether the mRNA tumor expression levels of thymidylate synthase (TS),
dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) at baseline are
potential predictors of clinical outcomes (response and survival) in patients treated with
this drug.

IV. Determine whether the serum level of TP is a potential prognostic indicator of clinical
outcomes (response and survival) in patients treated with this drug.

V. Determine whether the TS promoter polymorphism in peripheral blood is a potential
prognostic indicator of clinical outcomes (response and survival) in patients treated with
this drug.

VI. Determine the associations among the various measures of TS, DPD, and TP and clinical
outcomes (response and survival) in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in
the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.

Inclusion Criteria:

- Histologically confirmed primary non-squamous cell carcinoma (non-SCC) of the cervix

- Persistent or recurrent disease

- Eligible subtypes include:

- Adenocarcinoma

- Adenosquamous cell carcinoma

- Undifferentiated carcinoma

- Documented disease progression

- At least 1 unidimensionally measurable target lesion outside prior irradiation field

- At least 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan,
and MRI)

- At least 10 mm by spiral CT scan

- Received 1 prior systemic chemotherapy regimen for advanced, metastatic, or recurrent
non-SCC of the cervix

- Radiosensitizing chemotherapy administered in combination with primary
radiotherapy is not counted as a systemic chemotherapy regimen

- Tissue blocks from initial diagnosis, metastasis, or recurrence available for
submission to the GOG tissue bank

- Ineligible for higher priority Gynecologic Oncology Group (GOG) protocol (if one
exists), defined as any Temporarily closed GOG phase III protocol for the same patient
population

- Performance status - GOG 0-2

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- SGOT no greater than 2.5 times ULN

- Alkaline phosphatase no greater than 2.5 times ULN

- Creatinine clearance at least 50 mL/min

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- No Temporarily closed infection requiring antibiotics

- No grade 2 or greater sensory or motor neuropathy

- No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

- At least 3 weeks since prior biological or immunological anticancer agents

- No more than 1 prior non-cytotoxic biologic therapy or cytostatic regimen (e.g.,
monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction)
for recurrent or persistent non-SCC of the cervix

- See Disease Characteristics

- See Biologic therapy

- At least 3 weeks since prior chemotherapy and recovered

- No prior capecitabine

- No more than 1 prior cytotoxic chemotherapy regimen (either with single or combination
cytotoxic drug therapy)

- At least 1 week since prior hormonal anticancer therapy

- Concurrent hormone replacement therapy allowed

- See Disease Characteristics

- At least 3 weeks since prior radiotherapy and recovered

- Recovered from prior recent surgery

- At least 3 weeks since other prior anticancer therapy

- No prior cancer treatment that would preclude this study therapy