Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer

RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation therapy together with cisplatin is more effective than radiation therapy alone in treating patients with endometrial cancer.

PURPOSE: This randomized phase II trial is studying radiation therapy and cisplatin to see how well they work compared with radiation therapy alone in treating patients with recurrent endometrial cancer.

OBJECTIVES:

Primary

• Determine whether pelvic radiotherapy and cisplatin are more promising with respect to progression-free survival than pelvic radiotherapy alone in patients with recurrent endometrial cancer limited to the pelvis and vagina.

Secondary

• Compare the sites of recurrence in patients treated with these regimens.
• Compare overall survival of patients treated with these regimens.
• Compare the prognostic significance of the location (central pelvis versus vagina) and size of the recurrence, in addition to the prognostic significance in the salvage setting, in terms of histological subtype, grade, age, race, performance status, and the presence of lymph-vascular space involvement of the original tumor at the time of initial hysterectomy, in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo external-beam radiotherapy (EBRT) to the pelvis on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. After completion of EBRT, patients undergo intracavitary low-dose rate or high-dose rate brachytherapy* or low-dose rate interstitial brachytherapy*.
• Arm II: Patients undergo EBRT as in arm I and receive cisplatin IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Patients then undergo brachytherapy* as in arm I.

NOTE: *IMRT will be allowed for the entire course of therapy, this is for the treatment of the whole pelvis and/or the boost in those cases not undergoing brachytherapy.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

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

• Drug: cisplatin
  Given IV
• Radiation: brachytherapy
  Given intracavitarily or interstitially
• Radiation: external beam radiation therapy
  Given to the pelvis

• Active Comparator: Arm I
  Patients undergo external-beam radiotherapy (EBRT) to the pelvis on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. After completion of EBRT, patients undergo intracavitary low-dose rate or high-dose rate brachytherapy* or low-dose rate interstitial brachytherapy*
  Interventions:

  • Radiation: brachytherapy
  • Radiation: external beam radiation therapy
• Experimental: Arm II
  Patients undergo EBRT as in arm I and receive cisplatin IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Patients then undergo brachytherapy* as in arm I.
  Interventions:

  • Drug: cisplatin
  • Radiation: brachytherapy
  • Radiation: external beam radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of endometrial cancer, including the following histological subtypes:

  • Adenocarcinoma
  • Adenocarcinoma with squamous differentiation
  • Mucinous adenocarcinoma
  • Squamous cell carcinoma
  • Mixed carcinoma
  • Undifferentiated carcinoma
  • Clear cell adenocarcinoma
  • Serous adenocarcinoma
• Must have undergone prior complete hysterectomy and bilateral salpingo-oophorectomy at the time of original therapy

• Recurrent disease confined to the pelvis and/or vagina

  • No evidence of extrapelvic disease, including positive periaortic or inguino-femoral nodes by chest x-ray or CT scan

• Prior primary surgical debulking (including removal of gross symptomatic disease in the pelvis and/or vagina) allowed provided there is residual disease that is evaluable clinically and/or by CT scan or MRI

  • Exenterative surgery is not permissible

  • Patients who have undergone prior complete surgical resection of the recurrent tumor and have no evidence of residual disease evaluable clinically and by CT scan or MRI after resection are not eligible

    • Patients enrolled subsequent to revision 11 with complete resection of gross recurrent disease are eligible
• Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry

PATIENT CHARACTERISTICS:

• GOG performance status 0-2
• Life expectancy ≥ 3 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine normal OR creatinine clearance > 50 mL/min
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• No sensory or motor neuropathy > grade 1
• No septicemia or severe infection
• No circumstances that would preclude study participation
• No renal abnormalities (i.e., pelvic kidney, horseshoe kidney, or prior renal transplantation) that would require modification of radiation fields
• No other invasive malignancies within the past 5 years except nonmelanoma skin cancer
• No significant history of cardiac disease, including uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within the past 6 months
• No history of active collagen vascular disease

PRIOR CONCURRENT THERAPY:

• At least 6 months since prior hormone therapy and/or systemic chemotherapy
• No prior neoadjuvant chemotherapy for recurrent disease
• No prior exenterative surgery
• No prior vaginal, pelvic, or abdominal irradiation
• No prior chemotherapy directed at the present recurrent disease
• No prior cancer treatment that would preclude study treatment