Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2; Phase 1

Conditions: Radiation Toxicity; Cervical Cancer

Treatments: Radiation: Intracavitary brachytherapy; Radiation: External beam radiation therapy; Drug: Cisplatin; Drug: Amifostine trihydrate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00012012

CDR0000068472

RTOG-0116

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cisplatin, 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 radiation therapy with chemotherapy may kill more tumor cells. Drugs such as amifostine may protect normal cells from the side effects of radiation therapy.

PURPOSE: Phase I/II trial to study the effectiveness of combining cisplatin and radiation therapy with or without amifostine in treating patients who have stage IIIB or stage IVA cancer of the cervix.

Full description

OBJECTIVES:

• Determine the feasibility and tolerability of external beam radiotherapy, brachytherapy, and cisplatin in patients with para-aortic or high common iliac lymph node-positive carcinoma of the uterine cervix.
• Determine the feasibility and tolerability of this regimen with the addition of amifostine in these patients.
• Determine the efficacy of these 2 regimens, in terms of improving pelvic and para-aortic tumor control and distant metastases, in these patients.

OUTLINE:

• Phase I: Patients undergo external beam radiotherapy to the pelvis and para-aortic region 5 days a week for 5 weeks. Patients also undergo either intracavitary low-dose rate (LDR) brachytherapy in 2 applications beginning within 2 weeks after completion of external beam radiotherapy at 2-3 week intervals or 6 fractions of high-dose rate intracavitary brachytherapy over 8 weeks beginning as early as week 2 of external beam radiotherapy. Patients also receive cisplatin IV over 1 hour weekly for 6 weeks concurrently with external beam radiotherapy and once with LDR brachytherapy. Phase II proceeds only if toxicity in phase I is within expected parameters.
• Phase II: Patients receive external beam radiotherapy, brachytherapy, and cisplatin as in phase I. Patients also receive amifostine subcutaneously daily just before external beam radiotherapy and cisplatin. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Enrollment: 45 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven, locally advanced carcinoma of the uterine cervix

  • TNM classification stage IIIB or IVA

  • Disease metastatic to para-aortic or high common iliac lymph nodes

    • Prior complete surgical resection of involved lymph nodes or gross residual tumor involvement of a lymph node allowed

  • The following cellular types are eligible:

    • Squamous cell carcinoma
    • Adenocarcinoma
    • Adenosquamous carcinoma

  • The following cellular types are ineligible:

    • Small cell carcinoma
    • Carcinoid tumor
    • Glassy cell carcinoma
    • Clear cell carcinoma
    • Cystadenocarcinoma

• No metastatic disease outside of the pelvis (except to the para-aortic nodes)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• At least 6 months

Hematopoietic

• White blood cell count (WBC) at least 3,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• Alanine amino transferase (ALT) no greater than 2 times normal

Renal

• Creatinine no greater than 1.5 mg/dL (urinary diversion allowed)
• Corrected calcium normal

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent significant medical condition that would preclude study participation
• No insulin-dependent diabetes
• No other malignancy within the past 3 years except cutaneous basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic irradiation except transvaginal radiotherapy to control bleeding

Surgery

• See Disease Characteristics
• No prior tumor-directed surgery except lymph node biopsy/staging

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 2 patient groups

Radiation therapy plus cisplatin

Experimental group

Description:

Patients receive extended field external beam radiation therapy (RT) to the para-aortic region and pelvis, intracavitary brachytherapy with concurrent weekly cisplatin.

Treatment:

Radiation: Intracavitary brachytherapy

Drug: Cisplatin

Radiation: External beam radiation therapy

Radiation therapy plus cisplatin and amifostine

Experimental group

Description:

Patients receive extended field external beam radiation therapy (RT) to the para-aortic region and pelvis, intracavitary brachytherapy with concurrent weekly cisplatin and amifostine trihydrate.

Treatment:

Drug: Amifostine trihydrate

Radiation: Intracavitary brachytherapy

Drug: Cisplatin

Radiation: External beam radiation therapy