Bladder-sparing Trimodal Chemotherapy Produces Good Response in Patients with Muscle-invasive Bladder Cancer
In a phase II study reported in Lancet Oncology, Timur Mitin, MD, of Massachusetts General Hospital, and colleagues assessed the effects of adding paclitaxel or fluorouracil (5-FU) to radiation therapy plus cisplatin followed by adjuvant chemotherapy in a program of selected bladder preservation in patients with muscle-invasive bladder cancer. They found that the addition of paclitaxel or 5-FU to cisplatin and radiation therapy produced good response and bladder preservation rates but that completion of adjuvant therapy was difficult to achieve.
Study Details
In the multicenter, unblinded study (RTOG 0233), patients with T2–4a transitional cell carcinoma of the bladder were randomized to receive paclitaxel (n = 46) or 5-FU (n = 47) plus cisplatin with twice-daily radiation therapy. All patients had transurethral resection of bladder tumor and twice-daily radiation therapy to 40.3 Gy along with the allocated chemotherapy followed by assessment of response. Patients with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64.3 Gy with the same chemotherapy regimen. Patients received four cycles of adjuvant cisplatin, gemcitabine, and paclitaxel after the end of chemoradiotherapy. The primary endpoints were rates of treatment completion and toxicity. Median ages were 65 years in the paclitaxel group and 67 years in the 5-FU group, and most patients were male (83% and 85%).
Main Outcomes
Median follow-up was 5.0 years. In the paclitaxel group, 45 patients (98%) completed induction therapy, 39 (85%) completed induction and consolidation, and 31 (67%) completed the entire protocol. Grade 3 or 4 toxicity occurred in 16 patients (35%) during induction, 11 (24%) during consolidation, and in 34 (85%) of 40 during adjuvant therapy.
In the 5-FU group, 45 patients (96%) completed induction, 39 (83%) completed induction and consolidation, and 25 (53%) completed the entire protocol. Grade 3 or 4 toxicity occurred in 9 patients (19%) during induction, 12 (26%) during consolidation, and in 31 (76%) of 41 during adjuvant therapy.
Five paclitaxel patients (11%) and 3 5-FU patients (6%) had late grade 3 or 4 radiotherapy toxicities, and 11 (24%) and 16 (34%), respectively, developed late grade 3 or 4 toxicities unrelated to radiotherapy. Six paclitaxel patients (13%) and 3 5-FU patients (6%) discontinued treatment due to treatment-related toxicity.
Response and Survival
Complete responses were achieved in 72% (95% confidence interval [CI] = 57%–84%) of patients in the paclitaxel group and 62% (95% CI = 46%–76%) of patients in the 5-FU group. Five-year overall survival was 71% (95% CI = 57%–84%) in the paclitaxel group and 75% (95% CI = 62%–88%) in the 5-FU group, and 5-year bladder-intact survival was 67% (95% CI = 53%–81%) and 71% (95% CI = 57%–84%), respectively.
The investigators concluded, “[The study] showed that cisplatin with either paclitaxel or fluorouracil in combination with radiotherapy achieves good results in terms of cancer control and bladder preservation but completion of four cycles of systemic adjuvant chemotherapy is difficult. Frequency of toxic effects seemed similar for paclitaxel or fluorouracil regimens, and clinical judgment with physician experience should guide the selection of chemotherapy regimen.”
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