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).
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.



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.



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.



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.
Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Electronic address: dmichaelson1@partners.org.
M Dror
MD
Michaelson
NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Chen
C
Hu
Virginia Mason CCOP, Seattle, Washington.
Huong T
HT
Pham
Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Douglas M
DM
Dahl
Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Chin
C
Lee-Wu
University of Texas at San Antonio, San Antonio, Texas.
Gregory P
GP
Swanson
Virginia Mason CCOP, Seattle, Washington.
Jacqueline
J
Vuky
Intermountain Medical Center, Murray, Utah.
R Jeffrey
RJ
Lee
McGill University, Montréal, Quebec.
Luis
L
Souhami
Parkview Cancer Center, Parkview Hospital, Fort Wayne, Indiana.
Brian
B
Chang
NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
Asha
A
George
Cedars-Sinai Medical Center, Los Angeles, California.
Howard
H
Sandler
Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
William
W
Shipley
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects* / Q000379:methods*; D015653:Cystectomy; D005260:Female; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome; D014521:Urethra / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*
D000068878:Trastuzumab; D017239:Paclitaxel