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)

Journal Article · Sat Apr 01 04:00:00 EDT 2017 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2016.12.018· OSTI ID:22649889

Hu, Chen ^[1]; Pham, Huong T. ^[2]; Dahl, Douglas M.; Lee-Wu, Chin ^[3]; Swanson, Gregory P. ^[4]; Vuky, Jacqueline ^[2]; Lee, R. Jeffrey ^[5]; Souhami, Luis ^[6]; Chang, Brian ^[7]; George, Asha ^[1]; Sandler, Howard ^[8]; Shipley, William ^[3]

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1. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States)
2. Virginia Mason CCOP, Seattle, Washington (United States)
3. Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States)
4. University of Texas at San Antonio, San Antonio, Texas (United States)
5. Intermountain Medical Center, Murray, Utah (United States)
6. McGill University, Montréal, Quebec (Canada)
7. Parkview Cancer Center, Parkview Hospital, Fort Wayne, Indiana (United States)
8. Cedars-Sinai Medical Center, Los Angeles, California (United States)

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.

• OSTI ID: 22649889
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 97; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BLADDER
GY RANGE 10-100
IRRADIATION
NEOPLASMS
PATIENTS
RADIOTHERAPY
TOXICITY