Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer

Unicancer

Status and phase: Completed; Phase 3

Conditions: Anal Cancer

Treatments: Drug: cisplatin; Procedure: neoadjuvant therapy; Radiation: radiation therapy; Drug: fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT00003652

EU-98050

FNCLCC-FFCD-SFRO-ACCORD-3

CDR0000066744

Details and patient eligibility

About

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: This randomized phase III trial is studying different regimens of giving combination chemotherapy together with radiation therapy and comparing how well they work in treating patients with stage II or stage III anal cancer.

Full description

OBJECTIVES:

• Compare the efficacy of concurrent chemotherapy and radiotherapy with or without neoadjuvant chemotherapy with fluorouracil and cisplatin in patients with stage II or III anal canal cancer.
• Compare the efficacy of two levels of radiation dose in patients with stage II or III anal canal cancer.
• Compare the sphincter conservation of the anus by these regimens.
• Compare the effect of these regimens on survival and quality of life of these patients.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized to one of four treatment arms.

• Arm I: Patients receive induction chemotherapy consisting of fluorouracil IV over 24 hours on days 1-4 and cisplatin IV over 1 hour on day 1 or 2 every 4 weeks for 2 courses. Beginning 4 weeks later, patients receive chemoradiotherapy. This regimen consists of fluorouracil IV over 24 hours on days 1-4 and cisplatin IV over 1 hour on day 1 or 2 and repeated 4 weeks later, plus pelvic radiotherapy beginning on day 1 and continuing for 5 weeks (once a day, 5 days/week). Patients receive low dose radiotherapy directly to the tumor beginning 3 weeks later and continuing for 2 weeks.
• Arm II: Patients receive induction chemotherapy and chemoradiotherapy as in arm I, plus high dose radiotherapy directly to the tumor.
• Arm III (control arm): Patients receive chemoradiotherapy and low dose radiotherapy to the tumor as in arm I.
• Arm IV: Patients receive chemoradiotherapy and high dose radiotherapy to the tumor as in arm II.

After study treatment is completed, patients with nonfixed inguinal tumors may undergo surgical resection followed by radiotherapy or radiotherapy alone. Patients with fixed inguinal tumors may receive further radiotherapy alone.

Quality of life is assessed before treatment, at 2 months after completion of treatment, and at 5 years.

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

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 4 years.

Enrollment: 350 estimated patients

Sex: All

Ages: Under 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven nonmetastatic anal cancer

  • Anal/rectal junction OR

  • Anal/cutaneous junction with the majority of the tumor in the anal canal, above the junction

  • Epidermoid cancer (well-differentiated, fairly differentiated, or basaloid) OR

  • Cloacogenic cancer

  • Stage II or III

    • T2 at least 4 cm OR
    • T3 OR
    • T4, N0-3, M0 OR
    • T1, N1-3 OR
    • T2 (less than 4 cm), N1-3

• Tumors at least 4 cm in greatest dimension and/or tumors with lymph node invasion must be nonmetastatic by ultrasound

• No prior surgery to remove tumor

PATIENT CHARACTERISTICS:

Age:

• 80 and under

Performance status:

• WHO 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 11 g/dL (transfusion allowed)

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No cardiac condition contraindicating use of fluorouracil

Other:

• No prior malignancy within 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or breast
• No other serious medical or psychological condition
• No serious immunosuppression

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No prior endocrine therapy

Radiotherapy:

• No prior pelvic or inguinal radiotherapy

Surgery:

• See Disease Characteristics
• No prior definitive colostomy