The addition of paclitaxel or fluorouracil to cisplatin in combination with radiotherapy resulted in disease control and preservation of the bladder in patients with muscle-invasive bladder cancer, according to results of a multicenter phase 2 study.
However, the ability to complete four cycles of systemic adjuvant chemotherapy proved difficult for many patients, researchers wrote.
“Frequency of toxic effects seemed similar for paclitaxel or fluorouracil regimens, and clinical judgment with physician experience should guide the selection of chemotherapy regimen,” the researchers wrote.
Although other chemotherapies have been evaluated in this patient population, radiation plus cisplatin as a sensitizer is the most studied strategy for bladder preservation in the United States.
For the current study, researchers assigned 93 patients to paclitaxel plus cisplatin or fluorouracil plus cisplatin in combination with twice-daily radiotherapy in random block sizes per site based upon clinical T-stage (T2 vs. T3–4).
All patients had undergone transurethral resection of the bladder tumor and twice-daily radiotherapy to 40.3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after completion of chemoradiation.
Median follow-up was 5 years.
Ninety-eight percent of patients in the paclitaxel group completed induction; 85% completed induction and consolidation; and 67% completed the entire protocol with adjuvant chemotherapy.
Of those assigned fluorouracil, 96% completed induction; 83% completed induction and consolidation; and 53% completed the entire protocol with adjuvant chemotherapy.
Researchers reported complete responses in 72% (95% CI, 57%-84%) of patients in the paclitaxel group and 62% (95% CI, 57%-76%) of patients in the fluorouracil group.
Eighty-five percent of evaluable patients in the paclitaxel group and 76% of evaluable patients in the fluorouracil group had grade 3/4 toxicity during adjuvant chemotherapy.
Eleven percent of patients assigned to paclitaxel and 6% of patients assigned to fluorouracil went on to develop late grade 3/4 toxicities that were associated with radiotherapy. Twenty-four percent of patients assigned paclitaxel and 34% of patients assigned fluorouracil developed grade 3/4 toxicities that were not associated with radiotherapy.
One death occurred in the fluorouracil group. Treatment was discontinued due to toxicity in six patients assigned paclitaxel and three patients assigned fluorouracil.
"A long time has passed since the first studies assessed organ preservation as a therapeutic approach in muscle-invasive bladder cancer, but some questions remain," Alejandro Martinez-Fernandez, MD, of the department of medical oncology at the Hospital del Mar in Barcelona, Spain, wrote in an accompanying editorial. "Enough data exist about the success of trimodality treatments, but we are not able to clearly identify which patients should be treated with a strategy that seeks to preserve the bladder and which patients need to undergo immediate radical cystectomy. Another query to be solved is whether bladder preservation is associated with better quality of life.
"Side effects of chemotherapy or radiotherapy might overcome the theoretical benefits of preservation of the bladder and avoidance of morbidity of major surgery," Martinez-Fernandez wrote. "Phase 2 or retrospective studies can contribute relevant clinical data about the best treatment approach and selection of patients, but a phase 3 trial comparing surgery with bladder preservation will define the non-inferiority in terms of efficacy, and will provide higher levels of evidence to answer these questions."
For more information:
- Martinez-Fernandez A. Lancet. 2013;doi:10.1016/S1470-2045(13)70299-7.
- Mitin T. Lancet.2013; doi:10.1016/S1470-2045(13)70255-9.
Disclosure:The study was funded by the NCI.