- The rate of freedom from distant metastasis at three years surpassed 75% with both the established chemoradiation regimen for trimodality therapy and the investigational regimen: low-dose gemcitabine and once-daily radiation
- Rates of bladder preservation and complete response to induction chemotherapy were high with both regimens
- Both regimens were well tolerated
Bladder-preserving trimodality therapy is now accepted as a standard treatment for muscle-invasive bladder cancer. A series of trials by the Radiation Therapy Oncology Group (RTOG) have established that fluorouracil/cisplatin and radiation twice a day (FCT) is an effective chemoradiation regimen of trimodality therapy.
However, many patients with bladder cancer are poor candidates for cisplatin, especially those with renal impairment or hearing loss. A randomized phase II trial led by William U. Shipley, MD, chair of the Genitourinary Oncology Unit at Massachusetts General Hospital, suggests that a regimen incorporating concurrent low-dose gemcitabine and once-daily radiation (GD) is a reasonable alternative chemoradiation regimen. The results are published in the Journal of Clinical Oncology.
This trial was conducted at 10 centers in the United States and Canada from December 2008 through February 2014. Patients with cT2-4a muscle-invasive bladder cancer were randomly assigned to FCT (n=33) or GD (n=33) as the chemoradiation component of trimodality therapy. The median follow-up was 4.3 years for all patients and 5.1 years (range, 0.4 to 7.8 years) for the 51 patients alive at the time of reporting.
Patients underwent transurethral resection and induction chemoradiation to 40 Gy. Those who achieved a complete response received consolidation chemoradiation to 64 Gy; others underwent cystectomy. In the experimental arm, induction and consolidation chemotherapy consisted of gemcitabine 27 mg/m2 delivered twice weekly.
Adjuvant chemotherapy, consisting of cisplatin and gemcitabine, was also administered. If patients could not tolerate cispltain, paclitaxel was used as a substitute.
The primary endpoint was the rate of freedom from distant metastasis at three years (DMF3). The investigators assessed whether either regimen exceeded a DMF3 benchmark of 75% (the study was not statistically powered to compare the two regimens).
In the FCT group, the DMF3 rate was 78% (21 of 27 evaluable patients), with a 95% CI of 65-91%. In the GD group, the rate was 84% (21 of 25 evaluable patients), with a 95% CI of 72-96%. Both groups met the prespecified 75% benchmark.
The bladder-intact distant metastasis-free survival rate at three years was 67% in the FCT arm and 72% in the GD arm. Rates of complete response to induction chemoradiation were 88% and 78%, respectively. All of these rates compared favorably with the results of previous RTOG trials.
Treatment-related grade 3/4 adverse events were noted in 64% of patients in the FCT arm and 55% of patients in the GD arm during treatment. During the first six months after the end of treatment, the respective rates were 25% and 16%. The rates in both time periods were statistically similar.
About half of grade 3/4 events were hematologic, and only two or three gastrointestinal or genitourinary events were observed in each arm.
No definitive conclusion can be drawn about the toxicity of once-daily versus twice-daily radiation as part of trimodality therapy, since the patients in the two treatment arms received different chemotherapy regimens.
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