Chemotherapy and Radiation Therapy in Treating Patients With Stage II or Stage III Bladder Cancer That Was Removed by Surgery
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: induction cisplatin; induction 5-fluorouracil; induction gemcitabine; Induction BID radiation therapy; Induction QD radiation therapy; Consolidation BID radiation therapy; Consolidation QD radiation therapy; consolidation gemcitabine; consolidation 5-fluorouracil; consolidation cisplatin; radical cystectomy; Post-Induction Chemoradiotherapy Endoscopic Response Evaluation; adjuvant gemcitabine; adjuvant cisplatin
Intervention description: 15 mg/m^2 administered as a 60-minute infusion on days 1,2,3,8,9,10,15,16,17.; 400mg/m^2 administered as a 24-hour infusion on days 1,2,3, and 15,16,17.; 27 mg/m^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15, 18, 22, 25.; Twice daily (BID) on days 1-5,8-12,15-17. The first daily treatment consists of 1.6 Gy delivered to the pelvis. The second fraction consists of 1.5 Gy to the bladder for the first 5 treatment days. Then, 1.5 Gy is delivered to bladder tumor volume as the second treatment for the remaining 8 treatment days. The bladder tumor volume receives a total of 40.3 Gy.; Once daily (QD) on days (1-5,8-12,15-19,22-26). For the first 10 treatment days, 2 Gy is delivered to the pelvis. Then, 2 Gy is delivered to the bladder for the next 4 treatment days, followed by 2 Gy to the bladder tumor volume for the remaining 6 treatment days. The bladder tumor volume receives a total of 40 Gy.; Twice daily (BID) for 8 days on days 1,2,3,4,5,8,9,10 of consolidation. 1.5 Gy per fraction for a total of 24 Gy delivered to the pelvis.; Once daily (QD) pelvic radiation therapy for 12 days on days 1-5,8-12,15-16 of consolidation. 2 Gy per fraction for a total of 24 Gy delivered to the pelvis.; 27 mg/m^2 administered as a 30-minute infusion on days 1, 4, 8, 11, 15 of consolidation.; 400 mg/m^2 administered as a 24-hour infusion on days 1, 2, 3 and 8, 9, 10 of consolidation.; 15 mg/m^2 administered as a sixty-minute infusion on days 1, 2, 8, 9 of consolidation.; Operable patients who have a pT1 or worse tumor response on re-evaluation following initial transurethral resection and induction chemoradiotherapy will have a radical cystectomy 3-8 weeks following the post-induction response evaluation.; Urine cytology, cystoscopy, tumor site transurethral biopsy, and bimanual examination after biopsy.; 1000 mg/m^2 administered intravenously over 30-60 minutes (preferably 30 minutes) on days 1 and 8 of each 21-day cycle for four cycles.; 70 mg/m^2 administered as a sixty-minute infusion on day 1 of each 21-day cycle for four cycles.
Intervention MeSH terms: Cisplatin; Gemcitabine; Fluorouracil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage II bladder cancer; stage III bladder cancer; transitional cell carcinoma of the bladder

Summary:

      RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and gemcitabine, work
      in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells.
      Giving chemotherapy together with radiation therapy may kill more tumor cells.

      PURPOSE: This randomized phase II trial is studying two different chemotherapy and radiation
      therapy regimens to see how they work in treating patients with stage II or stage III bladder
      cancer that was removed by surgery.
    

Eligibility criteria:

        Inclusion criteria:

          1. Pathologically (histologically or cytologically) proven diagnosis of primary carcinoma
             of the bladder (transitional cell cancer) within 8 weeks of registration. Operable
             patients whose tumors are primary carcinomas of the bladder and exhibit histologic
             evidence of muscularis propria invasion and are American Joint Committee on Cancer
             (AJCC) clinical stages T2-T4a, Nx or N0, M0 (Appendix IV) without hydronephrosis;
             patients who have involvement of the prostatic urethra with transitional cell cancer
             (TCC) that was visibly completely resected and no evidence of stromal invasion of the
             prostate remain eligible. T2a, T2b, T3a, T3b -substages‖ are not usually able to be
             determined with clinical (TURBT) staging.

          2. If radiologic evaluation of a lymph node is interpreted as "positive", this must be
             evaluated further either by lymphadenectomy or percutaneous needle biopsy. Patients
             with histologically or cytologically confirmed node metastases will not be eligible.

          3. Patients must have an adequately functioning bladder after thorough evaluation by an
             urologist and have undergone as thorough a transurethral resection of the bladder
             tumor as is judged safely possible.

          4. Patients must be considered able to tolerate systemic chemotherapy combined with
             pelvic radiation therapy, and a radical cystectomy by the joint agreement of the
             participating Urologist, Radiation Oncologist, and Medical Oncologist.

          5. History and physical examination including weight, performance status, and body
             surface area within 8 weeks prior to study registration

          6. Zubrod Performance Status ≤ 1

          7. Age ≥ 18

          8. Complete blood count (CBC)/differential obtained no more than 4 weeks prior to
             registration on study, with adequate bone marrow function defined as follows:

               -  8.1 White blood cell count (WBC) ≥ 4000/ml

               -  8.2 Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;

               -  8.3 Platelets ≥ 100,000 cells/mm3;

               -  8.4 Hemoglobin (hgb) ≥ 10.0 mg/dl (Note: The use of transfusion or other
                  intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.);

          9. Serum creatinine of 1.5 mg% or less; serum bilirubin of 2.0 mg% or less; creatinine
             clearance of 60 ml/min or greater no more than 4 weeks prior to registration; Note:
             Calculated creatinine clearance is permissible. If the creatinine clearance is > 60
             ml/min, then a serum creatinine of up to 1.8 mg% is allowable at the discretion of the
             study chair;

         10. Serum pregnancy test for female patients of childbearing potential, ≤ 72 hours prior
             to study entry; women of childbearing potential and male participants must practice
             adequate contraception.

         11. Patient must be able to provide study-specific informed consent prior to study entry.

        Exclusion criteria:

          1. Evidence of tumor-related hydronephrosis

          2. Evidence of distant metastases or histologically or cytologically proven lymph node
             metastases

          3. Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy

          4. A prior or concurrent malignancy of any other site or histology unless the patient has
             been disease-free for ≥ 5 years except for non-melanoma skin cancer and/or stage T1a
             prostate cancer or carcinoma in situ of the uterine cervix

          5. Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b
             disease are considered to have unresectable disease

          6. Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such
             as an aminoglycoside)

          7. Severe, active co-morbidity, defined as follows:

               -  7.1 Unstable angina and/or congestive heart failure requiring hospitalization
                  within the last 6 months;

               -  7.2 Transmural myocardial infarction within the last 6 months;

               -  7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of registration;

               -  7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory
                  illness requiring hospitalization or precluding study therapy at the time of
                  registration;

               -  7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation
                  defects; note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol.

               -  7.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for
                  Disease Control (CDC) definition; note, however, that HIV testing is not required
                  for entry into this protocol. The need to exclude patients with AIDS from this
                  protocol is necessary because the treatments involved in this protocol may be
                  significantly immunosuppressive. Protocol-specific requirements may also exclude
                  immuno-compromised patients.

          8. Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception; this exclusion is
             necessary because the treatment involved in this study may be significantly
             teratogenic.

          9. Prior allergic reaction to the study drug(s) involved in this protocol