SAN DIEGO – Cisplatin plus paclitaxel and cisplatin plus 5-fluorouracil induction regimens are equally effective, and can be combined with radiation and transurethral resection in a bladder-sparing protocol, preliminary results from an ongoing, randomized, phase II trial show.
Dr. Anthony L. Zietman
Both regimens produce significant acute toxicity, yet more than 90% of patients completed induction and more than 80% completed consolidation without deviation, Dr. Anthony L. Zietman reported at the annual meeting of the American Society for Radiation Oncology.
After a median of 3 years, 73% of patients in the paclitaxel/cisplatin arm and 69% in the 5-FU/cisplatin arm were alive with intact bladders. The difference was not statistically significant.
"Adjuvant therapy remains a challenge after both regimens, with low rates of completion," said Dr. Zietman, professor of radiation oncology at Massachusetts General Hospital and Harvard Medical School, Boston. "This is a problem because many of these patients have occult micrometastatic disease, so we do want nontoxic adjuvant therapy."
In the RTOG (Radiation Therapy Oncology Group) 0233 study funded by the National Cancer Institute, Dr. Zietman and his associates at 33 institutions enrolled 97 patients with muscle-invading bladder cancer.
All patients underwent a transurethral resection and then were randomized into two chemotherapy arms: paclitaxel (50 mg/m2 weekly) plus cisplatin (15 mg/m2 on 3 days per week), or 5-FU (400 mg/m2 on 3 days per week on alternate weeks) plus the same cisplatin schedule. Patients in both arms also received radiotherapy twice daily to a total of 64.3 Gy, followed by adjuvant cisplatin/gemcitabine/paclitaxel chemotherapy.
Four patients were not eligible to complete the trial, leaving 46 in the paclitaxel/cisplatin arm and 47 in the 5-FU/cisplatin arm. Median follow-up was 3 years. The median age of patients was 66 years, 84% were men, and 95% had T2 disease.
Statistically similar proportions of patients in both arms had grade 2 or 3 toxicity during chemoradiation (70% in the paclitaxel/cisplatin arm and 62% in the 5-FU/cisplatin arm). The proportion with late toxicity reaching grade 3 or higher was also similar between the two groups (6% and 4%, respectively). The only case of grade 4 toxicity occurred in the paclitaxel/cisplatin arm.
"The big problem with the trial is with the adjuvant chemotherapy," Dr. Zietman said, noting that 86% of patients in the paclitaxel/cisplatin arm and 76% in the 5-FU/cisplatin arm had grade 3 or 4 toxicity during the later adjuvant treatment.
Dr. Zietman, the immediate past president of ASTRO, reported that 98% of patients in the paclitaxel/cisplatin arm completed induction; while 4 had grade 4 toxicity during induction, 11 had grade 4 toxicity during adjuvant therapy. Similarly, 96% of patients in the 5-FU/cisplatin arm completed induction; only 1 had grade 4 toxicity during induction, but 15 had grade 4 toxicity during adjuvant therapy.
The adjuvant cisplatin/gemcitabine/paclitaxel regimen "is standard chemotherapy given to [patients] after a cystectomy, but it really was a struggle to get them through it," he said. "It didn’t matter which chemotherapy regimen had been used up front. The outback chemotherapy was difficult. It was toxic."
After induction therapy, 87% of patients in the paclitaxel/cisplatin arm and 79% in the 5-FU/cisplatin arm were downstaged to T0, Ta, and Tcis bladder cancer; the difference was not statistically significant. Complete response was also statistically similar between the two arms (72% and 62%, respectively).
To date, Dr. Zietman concluded, "both regimens produce similarly high rates of tumor response and bladder preservation. I think it leaves you with a choice. Either regimen can be used."
Dr. Zietman said that he had no financial conflicts to disclose.