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 ****)
Mené sur 68 patients atteints d'un carcinome urothélial invasif de la vessie traité par chirurgie transurétrale, cet essai de phase I/II évalue, du point de vue de la toxicité, la possibilité d'ajouter le trastuzumab au paclitaxel dans le cadre d'une radiothérapie adjuvante
Purpose : Bladder 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 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. 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 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. Conclusions : In 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.