PMID- 28333021 OWN - NLM STAT- MEDLINE DCOM- 20170710 LR - 20220321 IS - 1879-355X (Electronic) IS - 0360-3016 (Print) IS - 0360-3016 (Linking) VI - 97 IP - 5 DP - 2017 Apr 1 TI - A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524). PG - 995-1001 LID - S0360-3016(16)33592-1 [pii] LID - 10.1016/j.ijrobp.2016.12.018 [doi] AB - PURPOSE: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. METHODS AND MATERIALS: Sixty-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 results. 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. RESULTS: A 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 1 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. CONCLUSIONS: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Michaelson, M Dror AU - Michaelson MD AD - Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Electronic address: dmichaelson1@partners.org. FAU - Hu, Chen AU - Hu C AD - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Pham, Huong T AU - Pham HT AD - Virginia Mason CCOP, Seattle, Washington. FAU - Dahl, Douglas M AU - Dahl DM AD - Massachusetts General Hospital Cancer Center, Boston, Massachusetts. FAU - Lee-Wu, Chin AU - Lee-Wu C AD - Massachusetts General Hospital Cancer Center, Boston, Massachusetts. FAU - Swanson, Gregory P AU - Swanson GP AD - University of Texas at San Antonio, San Antonio, Texas. FAU - Vuky, Jacqueline AU - Vuky J AD - Virginia Mason CCOP, Seattle, Washington. FAU - Lee, R Jeffrey AU - Lee RJ AD - Intermountain Medical Center, Murray, Utah. FAU - Souhami, Luis AU - Souhami L AD - McGill University, Montreal, Quebec. FAU - Chang, Brian AU - Chang B AD - Parkview Cancer Center, Parkview Hospital, Fort Wayne, Indiana. FAU - George, Asha AU - George A AD - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. FAU - Sandler, Howard AU - Sandler H AD - Cedars-Sinai Medical Center, Los Angeles, California. FAU - Shipley, William AU - Shipley W AD - Massachusetts General Hospital Cancer Center, Boston, Massachusetts. LA - eng GR - U10 CA180868/CA/NCI NIH HHS/United States GR - U10 CA037422/CA/NCI NIH HHS/United States GR - U10 CA021661/CA/NCI NIH HHS/United States GR - U10 CA180867/CA/NCI NIH HHS/United States GR - U10 CA180822/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20161219 PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - P188ANX8CK (Trastuzumab) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Chemoradiotherapy, Adjuvant/*adverse effects/*methods MH - Cystectomy MH - Female MH - Gastrointestinal Diseases/diagnosis/*etiology/prevention & control MH - Humans MH - Male MH - Middle Aged MH - Muscle, Smooth/pathology MH - Neoplasm Invasiveness MH - Paclitaxel/administration & dosage MH - Radiation Injuries/diagnosis/*etiology/prevention & control MH - Trastuzumab/administration & dosage MH - Treatment Outcome MH - Urethra/surgery MH - Urinary Bladder Neoplasms/diagnosis/pathology/*therapy PMC - PMC5536836 MID - NIHMS879983 COIS- Conflicts of interest: Dr. Souhami reports travel expenses from Varian Medical Systems, outside the submitted work. Dr. Sandler reports grants from ACR-RTOG, during the conduct of the study; consulting and advisory fees from Sanofi, Medivation, Clovis Oncology, Janssen, Ferring, NANT Health, and Blue Earth Diagnostics, speaking fees from Varian, outside the submitted work. EDAT- 2017/03/24 06:00 MHDA- 2017/07/14 06:00 PMCR- 2018/04/01 CRDT- 2017/03/24 06:00 PHST- 2016/10/19 00:00 [received] PHST- 2016/11/23 00:00 [revised] PHST- 2016/12/13 00:00 [accepted] PHST- 2017/03/24 06:00 [entrez] PHST- 2017/03/24 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2018/04/01 00:00 [pmc-release] AID - S0360-3016(16)33592-1 [pii] AID - 10.1016/j.ijrobp.2016.12.018 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):995-1001. doi: 10.1016/j.ijrobp.2016.12.018. Epub 2016 Dec 19.