Docetaxel and Radiation Therapy in Treating Patients With Stage II, Stage III, or Stage IV Cervical Cancer

OBJECTIVES:

Primary

- Determine the recommended phase II dose (RPTD) of docetaxel when administered with
radiotherapy in patients with stage IIB-IVA cervical cancer. (Phase I)

- Assess the progression-free survival of patients treated with this regimen. (Phase II)

Secondary

- Determine the safety, feasibility, and toxicity of this regimen in these patients.
(Phase I)

- Assess the toxicity of this regimen at the RPTD in these patients. (Phase II)

- Determine the response in patients treated with this regimen. (Phase II)

OUTLINE: This is a phase I, nonrandomized, prospective, dose-escalation study of docetaxel
followed by an open-label phase II study.

- Phase I: Patients receive docetaxel IV over 30 minutes on day 1. Treatment repeats
weekly for up to 6 courses in the absence of disease progression or unacceptable
toxicity. Patients also undergo concurrent pelvic external-beam radiotherapy (EBRT)
once daily 5 days a week for 5 weeks. Beginning 1-2 weeks after completion of EBRT,
patients receive one or two applications of intracavitary low-dose-rate brachytherapy
(LDR BT) comprising cesium-137.

Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPTD) is the
dose below the MTD.

- Phase II: Patients receive docetaxel at the RPTD, EBRT, and LDR BT as in phase I.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the uterine
cervix

- Locally advanced (stage IIB- IVA) disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 8.0 g/dL

- WBC ≥ 3,000/mm^3

- Creatinine normal

- Bilirubin normal

- SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) if alkaline phosphatase (AP) ≤
ULN OR AP ≤ 4 times ULN if SGOT and SGPT ≤ ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for up to 6 months after
completion of study treatment

- No history of severe allergic reactions to agents containing polysorbate 80

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would preclude compliance with
study requirements

- No peripheral neuropathy ≥ grade 2

- No HIV positivity

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior unrelated therapy and recovered

- No prior chemotherapy or pelvic radiotherapy

- No other concurrent investigational agents or anticancer agents or therapies