Advertisement

Assessment of Tolerability, Response and Complications of Concurrent Chemoradiation With Capecitabine and Cisplatin in Muscle-Invasive Bladder Cancer; A Single Arm Study

      Abstract

      Purpose

      To evaluate the feasibility, tolerance and efficacy of cisplatin+capecitabine as a proposed combination in concurrent chemoradiotherapy for patients with muscle-invasive bladder cancer (MIBC).

      Methods

      MIBC patients with stage T2-T4aN0M0 participated in this single-arm clinical trial. After maximal TURBT, 66Gy/33 daily fractions of radiation were administered with concurrent chemotherapy of cisplatin (35 mg/m2) and capecitabine (625 mg/m2). The primary endpoint was treatment tolerability, defined as receiving capecitabine+cisplatin combination for at least 5 weeks during radiation therapy. The secondary endpoints included complete response (CR) and acute toxicity rates.

      Results

      This study included 19 MIBC patients from 2018 to 2019. Eighteen patients (94.7%, 95%CI: 75.4-99.0) completed the planned treatment course. Only one patient (5.26%, 95%CI: 0.9-24.6) discontinued the treatment due to grade-3 GI toxicity. Among those who completed the treatment, CR was seen in 12 patients (66.7%, 95% CI = 44.4-88.9) with no grade ≥ 3 toxicities. The most common grade-2 side effects during therapy were renal complications (57.9%), and the only grade-2 complication after therapy was urinary-related (11.1%). The median follow-up was 31 months and the median overall survival (OS) was 31 months. The 2-year OS was 78% (95% CI 58.4-97.6), Cystectomy-free survival was 61% (95% CI: 37.5-84.5), and the median OS after recurrence was 13 months. Distant metastases were the first type of recurrence in most patients with a recurrence, which occurred in 7 (36.8%) patients. Median metastasis-free survival (MFS) was 30 months, and 2-year MFS was 66% (95% CI:45-87).

      Conclusion

      The promising tolerability rate seen with concurrent cisplatin+capecitabine in this study was comparable to the available literature. Thus, this combination concurrently with radiation warrants further studies in the context of chemoradiotherapy of MIBC.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ploeg M
        • Aben KK
        • Kiemeney LA.
        The present and future burden of urinary bladder cancer in the world.
        World J Urol. 2009; 27: 289-293
        • Pakzad R
        • Mohammadian-Hafshejani A
        • Mohammadian M
        • et al.
        Incidence and mortality of bladder cancer and their relationship with development in Asia.
        Asian Pac J Cancer Prev. 2015; 16: 7365-7374
        • Scosyrev E
        • Noyes K
        • Feng C
        • Messing E
        Sex and racial differences in bladder cancer presentation and mortality in the US.
        Cancer. 2009; 115: 68-74
        • Rödel C
        • Weiss C
        • Sauer R.
        Combined systemic therapy and radiotherapy for bladder cancer.
        Strahlentherapie und Onkologie. 2007; 183: 29-31
        • Dunst J
        • Sauer R
        • Schrott KM
        • Kühn R
        • Wittekind C
        • Altendorf-Hofmann A.
        Organ-sparing treatment of advanced bladder cancer: a 10-year experience.
        Int J Radiat Oncol Biol Phys. 1994; 30: 261-266
        • Tester W
        • Porter A
        • Asbell S
        • et al.
        Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12.
        Int J Radiat Oncol Biol Phys. 1993; 25: 783-790
        • Kaufman DS
        • Winter KA
        • Shipley WU
        • et al.
        The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response.
        Oncologist. 2000; 5: 471-476
        • Housset M
        • Maulard C
        • Chretien Y
        • et al.
        Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study.
        J Clin Oncol. 1993; 11: 2150-2157
        • Rödel C
        • Grabenbauer GG
        • Kühn R
        • et al.
        Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results.
        J Clin Oncol. 2002; 20: 3061-3071
        • Arcangeli G
        • Arcangeli S
        • Strigari L
        A systematic review and meta-analysis of clinical trials of bladder-sparing trimodality treatment for muscle-invasive bladder cancer (MIBC).
        Crit Rev Oncol/Hematol. 2015; 94: 105-115
        • Chang SS
        • Bochner BH
        • Chou R
        • et al.
        Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline.
        J Urol. 2017; 198: 552-559
        • James ND
        • Hussain SA
        • Hall E
        • et al.
        Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer.
        N Engl J Med. 2012; 366: 1477-1488
        • Patel B
        • Forman J
        • Fontana J
        • Frazier A
        • Pontes E
        • Vaishampayan U.
        A single institution experience with concurrent capecitabine and radiation therapy in weak and/or elderly patients with urothelial cancer.
        Int J Radiat Oncol Biol Phys. 2005; 62: 1332-1338
        • Walko CM
        • Lindley C.
        Capecitabine: a review.
        Clin Therap. 2005; 27: 23-44
        • Basch E
        • Pugh SL
        • Dueck AC
        • et al.
        Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.
        Int J Radiat Oncol Biol Phys. 2017; 98: 409-418
        • Mitin T
        • Hunt D
        • Shipley WU
        • et al.
        Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial.
        Lancet Oncol. 2013; 14: 863-872
        • Coen JJ
        • Zhang P
        • Saylor PJ
        • et al.
        Bladder preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase II trial.
        J Clin Oncol. 2019; 37: 44-51
        • Kent E
        • Sandler H
        • Montie J
        • et al.
        Combined-modality therapy with gemcitabine and radiotherapy as a bladder preservation strategy: results of a phase I trial.
        J Clin Oncol. 2004; 22: 2540-2545
        • Oh KS
        • Soto DE
        • Smith DC
        • Montie JE
        • Lee CT
        • Sandler HM.
        Combined-modality therapy with gemcitabine and radiation therapy as a bladder preservation strategy: long-term results of a phase I trial.
        Int J Radiat Oncol Biol Phys. 2009; 74: 511-517
        • Schuettfort VM
        • Pradere B
        • Quhal F
        • et al.
        Incidence and outcome of salvage cystectomy after bladder sparing therapy for muscle invasive bladder cancer: a systematic review and meta-analysis.
        World J Urol. 2021; 39: 1757-1768
        • Horwich A
        • Dearnaley D
        • Huddart R
        • et al.
        A randomised trial of accelerated radiotherapy for localised invasive bladder cancer.
        Radiother Oncol. 2005; 75: 34-43