Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating women who have stage III or stage IV endometrial cancer.

OBJECTIVES:

• Determine the feasibility of doxorubicin and cisplatin followed by whole abdominal radiotherapy in patients with stage III or IV endometrial cancer.
• Determine the acute and chronic toxic effects, in particular, severe and life-threatening gastrointestinal, hepatic, and hematologic toxic effects, of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin IV and cisplatin IV on day 1. Treatment repeats every 3 weeks for 3 courses. Patients then undergo whole abdominal radiotherapy 5 days a week for 4-6 weeks.

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

PROJECTED ACCRUAL: A total of 21-53 patients will be accrued for this study within 3.5 years.

• Drug: cisplatin
• Drug: doxorubicin hydrochloride
• Procedure: adjuvant therapy
• Radiation: radiation therapy

• Fowler JM, Brady WE, Grigsby PW, Cohn DE, Mannel RS, Rader JS. Sequential chemotherapy and irradiation in advanced stage endometrial cancer: A Gynecologic Oncology Group phase I trial of doxorubicin-cisplatin followed by whole abdomen irradiation. Gynecol Oncol. 2009 Mar;112(3):553-7. Epub 2009 Jan 9.
• Fowler JM, Brady WE, Cohn DE, et al.: Sequential chemotherapy and irradiation in advanced-stage endometrial cancer: a Gynecologic Oncology Group phase I trial of doxorubicin-cisplatin followed by whole-abdomen irradiation. [Abstract] Society of Gynecologic Oncologists, 2007 Annual Meeting on Women's Cancer, March 3-7, 2007, San Diego, CA. A-230, 2007.

DISEASE CHARACTERISTICS:

• Histologically confirmed endometrial cancer including 1 of the following subtypes:

  • Clear cell carcinoma
  • Serous papillary carcinoma
  • Endometrioid adenocarcinoma

• Stage III or IV disease

  • Positive adnexa
  • Metastases to serosa, bowel mucosa, abdomen
  • Positive pelvic or paraaortic nodes
  • Positive pelvic washings or vaginal involvement within the radiation port

• Tumor must be surgically reduced to 2 cm or less within 8 weeks of study entry

  • Must have had a hysterectomy and bilateral salpingo oophorectomy
• No recurrent disease

• No distant metastases outside of abdominopelvic area, including:

  • Parenchymal liver metastases
  • Lung metastases
  • Positive inguinal lymph nodes
  • Positive supraclavicular nodes
  • Pleural effusion with malignant cytology

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• GOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT and alkaline phosphatase no greater than 3 times ULN

Renal:

• Creatinine no greater than ULN

Cardiovascular:

• Cardiac ejection fraction greater than 50%

Other:

• No other prior or concurrent malignancy within the past 5 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior pelvic or abdominal radiotherapy
• No prior radiotherapy for other prior malignancy

Surgery:

• See Disease Characteristics