Phase III Randomized Study of Neoadjuvant Chemotherapy with MCV (MTX/CDDP/VBL) vs No Neoadjuvant Chemotherapy Followed by Radiotherapy plus CDDP for Selective Bladder Preservation Following TURB in Patients with Muscle-Invading Bladder Cancer
Basic Trial Information
|Phase III||Treatment||Completed||18 and over||NCI||RTOG-8903|
I. Determine, in a phase III randomized setting, whether neoadjuvant chemotherapy with MCV (methotrexate/cisplatin/vinblastine) significantly improves the rate of successful bladder preservation (tumor-free with good function) at 3 years. II. Determine whether, in the context of a potential bladder-preserving treatment regimen, neoadjuvant MCV chemotherapy reduces the rate of disease recurrence. III. Assess and compare the duration of disease-free survival, overall survival, and patterns of failure in patients receiving neoadjuvant MCV vs. no neoadjuvant chemotherapy (durability of local CR will be evaluated in patients with bladder preserved, and the frequency of subsequent development of metastases will be noted in all patients). IV. Evaluate the effects of neoadjuvant MCV chemotherapy on the sequelae from radiotherapy, surgery, or intravesical chemotherapy in these patients. V. Assess the value of cellular DNA analysis by flow cytometry in predicting patients whose tumors will achieve and maintain a CR to combined chemotherapy and radiotherapy.
Primary carcinoma of the bladder of any histology with histologic evidence of muscle invasion Clinical Stage T2-4a, NX, M0 No nodal metastasis allowed Suspicious nodes must be histologically negative Maximum tumor reduction (by TURB) required within 4 weeks of entry
Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior pelvic radiotherapy Surgery: Staging procedures and TURB with removal of as much of bladder tumor as possible required within 4 weeks of treatment Urinary diversion prior to treatment allowed Other: No concurrent nephrotoxic or ototoxic drugs (e.g., aminoglycosides)
Age: At least 18 Performance status: Karnofsky 70%-100% Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hemoglobin at least 10 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 1.7 mg/dL Creatinine clearance at least 60 mL/min Other: Patient must be able to tolerate systemic chemotherapy, pelvic radiotherapy, and possible cystectomy No second malignancy within 5 years except: Nonmelanomatous skin cancer Stage T1a prostatic cancer In situ cervical carcinoma
174 patients will be entered over about 2 years.
Randomized study. Following treatment on Arm I or II, patients who achieve CR and those who achieve incomplete response but are unsuited for surgery receive Consolidation therapy, while those incomplete responders who are suited for surgery undergo radical cystectomy. Arm I: 3-Drug Combination Chemotherapy followed by Radiotherapy plus Single-agent Chemotherapy. MCV: Methotrexate, MTX, NSC-740; Cisplatin, CDDP, NSC-119875; Vinblastine, VBL, NSC-49842; followed by small-field pelvic irradiation using external beam photons with energies of at least 4 MV (Co60 equipment is not acceptable); plus CDDP. Arm II: Radiotherapy plus Single-agent Chemotherapy. Small-field pelvic irradiation with equipment as in Arm I; plus CDDP. Consolidation: Radiotherapy plus Single-agent Chemotherapy. Small-field pelvic irradiation followed by cone-down boost with equipment as in Arm I; plus CDDP.
Chakravarti A, Winter K, Wu CL, et al.: Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 62 (2): 309-17, 2005.[PUBMED Abstract]
Shipley WU, Winter KA, Kaufman DS, et al.: Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol 16 (11): 3576-83, 1998.[PUBMED Abstract]
Shipley W, Winter K, Kaufman D, et al.: An RTOG phase III trial (#89-03) of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A1197, 311a, 1998.
Efstathiou JA, Bae K, Shipley WU, et al.: Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol 27 (25): 4055-61, 2009.[PUBMED Abstract]
Shipley WU, Bae K, Efstathiou JA, et al.: Late pelvic toxicity following bladder-sparing therapy in patients with invasive bladder cancer: analysis of RTOG 89-03, 95-06, 97-06, 99-06. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-14, S8, 2007.
Chakravarti A, Winter K, Wu C, et al.: Expression of the epidermal growth factor receptor (EGFR) is associated with improved outcome in muscle-invading bladder cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-713, 2002.
Trial Contact Information
Trial Lead Organizations
Radiation Therapy Oncology Group
Ph: 617-726-8146; 877-726-5130
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.