A Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab with Daily Irradiation or Paclitaxel Alone with Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates with Muscle-Invasive Bladder Cancer (Trial ****)

Publication date: Available online 19 December 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): M. Dror Michaelson, Chen Hu, Huong T. Pham, Douglas M. Dahl, Chin Lee-Wu, Gregory P. Swanson, Jacqueline Vuky, R. Jeffrey Lee, Luis Souhami, Brian Chang, Asha George, Howard Sandler, William Shipley
PurposeBladder preservation therapy is an effective treatment for muscle invasive urothelial carcinoma (UC). In this study we treated non-cystectomy candidates with daily radiation and weekly paclitaxel for seven weeks. Patients whose tumors exhibited her2/neu overexpression were additionally treated with weekly trastuzumab.Methods and MaterialsSixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (Group 1) or paclitaxel alone (Group 2). Groups were assigned on the basis of her2/neu immunohistochemistry. Patients received 1.8 Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival.ResultsA total of 20 evaluable patients were treated in Group 1, and 46 patients in Group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in Group 1 (35%) and 14 of 46 patients in Group 2 (30.4%). Protocol therapy was completed by 60% (Group 1) and 74% (Group 2) of patients. Most incompletions were due to toxicity and the majority of AEs were gastrointestinal, including one Grade 5 AE (Group 1). Two other deaths (both in Group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic or other toxicities were observed. The CR rate at 1 year was 72% for Group 1 and 68% for Group 2.ConclusionsIn patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with high completion rate and moderate toxicity. In patients with her2/neu+ positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.

Teaser

Standard treatment for muscle invasive urothelial cancer of the bladder is radical cystectomy. Bladder preservation with combination of radiation and chemotherapy is a well-established alternative to surgery. In this study we treated patients who were not surgical candidates with chemoradiation, to a high completion rate. Our findings suggest that in such patients radiation may be combined with weekly paclitaxel, and in her2/neu positive tumors with the further addition of trastuzumab, with moderate toxicity.


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