A Phase I Study of Whole Pelvic Radiation Therapy With Concomitant Cisplatin and Gemcitabine Chemotherapy in Patients With Cervical Carcinoma (Stages I-IV) Limited to the Pelvis
A Phase I Study of Whole Pelvic Radiation Therapy With Concomitant Cisplatin and Gemcitabine Chemotherapy in Patients With Cervical Carcinoma (Stages I-IV) Limited to the Pelvis
This phase I trial is studying the side effects and best dose of gemcitabine when given together with radiation therapy and cisplatin in treating patients with cervical cancer that has not spread beyond the pelvis. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining cisplatin with gemcitabine may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.
PRIMARY OBJECTIVES:
I. Determine the toxicity of pelvic radiotherapy and concurrent cisplatin and gemcitabine in patients with cervical carcinoma limited to the pelvis.
II. Determine the maximum tolerated dose (MTD) of gemcitabine in combination with cisplatin and pelvic radiotherapy in these patients.
SECONDARY OBJECTIVES:
I. Determine the progression-free and overall survival of patients treated with gemcitabine at the MTD in this regimen.
II. Determine the site of recurrence, local versus distant, in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of gemcitabine.
Patients receive gemcitabine IV over 30 minutes and cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36 in the absence of disease progression or unacceptable toxicity. Patients also undergo external whole pelvis radiotherapy once daily on days 1-5, 8-13, 15-20, 22-27, and 29-34. After completion of external beam radiotherapy, patients undergo intracavitary radiotherapy and parametrial radiotherapy. The total elapsed time for completion of all radiotherapy is not more than 8 weeks.
Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experiences dose-limiting toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Inclusion Criteria:
Histologically confirmed primary invasive carcinoma of the uterine cervix
Para-aortic lymph nodes negative by radiologic evaluation or by biopsy if CT scan is suspicious for adenopathy
No known metastases to scalene nodes or other organs outside the radiotherapy field
Study enrollment within 8 weeks of diagnosis
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 normal
SGOT no greater than 3 times normal
Creatinine less than 2.0 mg/dL
No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) that would require modification of radiotherapy fields
No ureteral obstruction allowed unless treated with stent or nephrostomy tube
Not pregnant
Fertile patients must use effective contraception
No septicemia or severe infection
No circumstance that would preclude study completion or follow-up
No other malignancy within the past 5 years except nonmelanoma skin cancer
No prior cytotoxic chemotherapy
No prior pelvic or abdominal radiotherapy
No prior therapy for this malignancy