Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II or Stage III Bladder Cancer

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2; Phase 1

Conditions: Bladder Cancer

Treatments: Procedure: conventional surgery; Drug: gemcitabine hydrochloride; Radiation: radiation therapy; Drug: cisplatin; Drug: paclitaxel

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003930

CDR0000067122

RTOG-9906

Details and patient eligibility

About

RATIONALE: Radiation therapy uses 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 radiation therapy with chemotherapy and surgery may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy plus combination chemotherapy in treating patients who have stage II or stage III bladder cancer that can be removed by surgery.

Full description

OBJECTIVES:

• Evaluate the safety and tolerability of induction chemoradiotherapy with paclitaxel and cisplatin followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy in patients with stage II or III muscle invasive carcinoma of the bladder previously treated with transurethral tumor resection.
• Evaluate the efficacy of transurethral tumor resection and induction chemoradiotherapy in achieving a complete response in this patient population.
• Assess the value of tumor parameters as prognostic factors for initial tumor response and recurrence-free survival in this patient population.

OUTLINE: Four to six weeks after prior transurethral resection, patients receive induction therapy comprising paclitaxel IV over 1 hour on days 1, 8, and 15, cisplatin IV over 1 hour on days 1, 2, 8, 9, 15, and 16, and radiotherapy twice daily on days 1-5, 8-12, and 17.

Four weeks after induction therapy, patients undergo urologic evaluation. At 1-2 weeks after evaluation, patients with complete response receive consolidation therapy comprising paclitaxel IV over 1 hour on days 1 and 8, cisplatin IV over 1 hour on days 1, 2, 8, and 9, and radiotherapy twice daily on days 1-5 and 8-10. Patients with poor tumor response undergo a cystectomy.

At 12 weeks postconsolidation therapy or 8 weeks post radical cystectomy, patients receive adjuvant chemotherapy comprising gemcitabine IV over 30-60 minutes followed by cisplatin IV over 1 hour every 3 weeks. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 3 years.

Enrollment: 84 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage II or III (T2-4a, Nx or N0, M0) primary carcinoma of the bladder with muscle invasion

  • Resectable disease
  • Prostatic urethral involvement with transitional cell carcinoma allowed, if completely resected and no evidence of stromal invasion
  • No tumor-related hydronephrosis

• Positive lymph node must be evaluated by lymphadenectomy or percutaneous needle biopsy

  • No nodal metastases

• No distant metastases

• No more than 6 weeks since prior transurethral resection of the bladder tumor

  • Functioning bladder

PATIENT CHARACTERISTICS:

Age:

• Adult

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10 g/dL
• White blood cell (WBC) count of at least 4,000/mm^3
• Absolute neutrophil count at least 1,800/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min

Other:

• No other prior or concurrent malignancy within the past 5 years except curatively treated nonmelanoma skin cancer, stage I prostate cancer, or carcinoma in situ of the cervix
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• Medically operable

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior pelvic radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No concurrent potential nephrotoxic or ototoxic drugs (e.g., aminoglycosides)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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84 participants in 1 patient group

Arm 1

Experimental group

Description:

Transurethral surgery with chemotherapy and radiation therapy followed by either selective bladder preservation or radical cystectomy followed by adjuvant chemotherapy.

Treatment:

Procedure: conventional surgery

Drug: gemcitabine hydrochloride

Drug: cisplatin

Radiation: radiation therapy

Drug: paclitaxel