Researchers has assessed effectiveness, safety, and tolerability of Paclitaxel or Fluorouracil when added to radiation plus Cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer.
In the randomised phase 2 trial, investigators enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA.
The patients were randomly allocated to receive Paclitaxel plus Cisplatin ( Paclitaxel group ) or Fluorouracil plus Cisplatin ( Fluorouracil group ) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage ( T2 vs T3-4 ). Patients and physicians were aware of treatment assignment.
All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40.3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response.
Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64.3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant Cisplatin – Gemcitabine - Paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, researchers recommended patients undergo cystectomy and adjuvant chemotherapy.
During the period 2002-2008, investigators enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5.0 years.
Of 46 patients in the Paclitaxel group, 45 ( 98% ) completed induction ( 16 [ 35% ] with grade 3-4 toxicity ), 39 ( 85% ) completed induction and consolidation ( 11 [ 24% ] with grade 3-4 toxicity due to consolidation ), and 31 ( 67% ) completed the entire protocol with adjuvant chemotherapy.
34 ( 85% ) of 40 assessable patients in the Paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy.
Of 47 patients in the Fluorouracil group, 45 ( 96% ) completed induction ( 9 [ 19% ] with grade 3-4 toxicity ), 39 ( 83% ) completed induction and consolidation ( 12 [ 26% ] had grade 3-4 toxicity due to consolidation ), and 25 ( 53% ) completed the entire protocol with adjuvant chemotherapy. 31 ( 76% ) of 41 assessable patients in the Fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy.
Five ( 11% ) patients treated with the Paclitaxel regimen and three ( 6% ) patients treated with the Fluorouracil regimen developed late grade 3-4 radiotherapy toxicities.
11 ( 24% ) patients treated with the Paclitaxel regimen and 16 ( 34% ) patients treated with the Fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy.
One patient ( in the Fluorouracil group ) died during follow-up.
Six ( 13% ) patients in the Paclitaxel group and in three ( 6% ) patients in the Fluorouracil group discontinued due to treatment-related toxicity. ( Xagena )
Mitin T et al, The Lancet Oncology 2013; 14: 863-872