SAN FRANCISCO—Bladder-preserving treatment with paclitaxel, trastuzumab, and daily irradiation is “appropriate” following transurethral surgery for patients with muscle-invasive bladder urothelial carcinoma not suitable for cystectomy, according to the initial report of a phase 1/2 Radiation Therapy Oncology Group (RTOG) study presented at the 2014 Genitourinary Cancers Symposium.

Although the response rate for HER2/neu-targeted therapy is “encouraging,” this trimodal treatment may “increase certain adverse events in this challenging population,” noted M. Dror Michaelson, MD, PhD, Clinical Director of the Genitourinary Cancer Center at Massachusetts General Hospital, Boston, MA, on behalf of the RTOG 0524 study investigators.

“Up to 50% of patients with urothelial carcinoma overexpress HER2/neu, which may be associated with reduced responsiveness to chemoradiation and reduced survival,” he stated. “Many patients with urothelial carcinoma have comorbidities that preclude surgery, creating a traditionally underserved population with worse outcomes.”

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In this study, patients with invasive bladder urothelial carcinoma (stages T2-T4a, N0-1, M0) underwent cystoscopic tumor resection. “Tumors were analyzed by HER2/neu immunohistochemistry (IHC) and assigned to chemotherapy group 1 (IHC 2+ or 3+; paclitaxel and trastuzumab) or [group] 2 (IHC-negative or 1+; paclitaxel alone),” he noted. “Concurrent weekly paclitaxel (50 mg/m2), weekly trastuzumab (group 1 only), and daily radiation (64.8 Gy total in 36 fractions) were given for 7 consecutive weeks.”

Group 1 comprised 21 patients with a median age of 80 years and group 2, 47 patients with a median age of 73 years. The primary endpoint, acute protocol-defined toxicity related to treatment, was observed in seven patients (33%) in group 1 and 14 patients (30%) in group 2. The most common grade 3 or higher adverse events were marrow suppression (43% in group 1 and 17% in group 2), diarrhea (33% and 30%), and hyponatremia (14% and 4%).

“Three deaths on study were attributed to colonic perforation, pneumonia, and sudden death,” Dr. Michaelson noted. A total of 72% of patients completed radiation in group 1 and 85% in group 2; full-dose chemotherapy completion rates were 52% and 51%, respectively.

When patients were evaluated by cystoscopy and/or tumor biopsy at 12 weeks, nine (69%) of 13 patients in group 1 and 19 (58%) of 33 patients in group 2 had a complete response. The remaining patients did not undergo these procedures.

The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).


  1. Michaelson MD, Hu C, Pham HT, et al. Abstract LBA287. Presented at: 2014 Genitourinary Cancers Symposium. Jan. 30-Feb. 1, 2014; San Francisco.