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CHEMOTHERAPY AND BLADDER CANCER

CHEMOTHERAPY AND BLADDER CANCER. Walter Stadler, MD, FACP University of Chicago. Anatomy as a Problem. One score and seven years ago…. The metastatic d. problem 1985 - MVAC first reported 1997 - Gemcitabine first reported to have activity GC found comparable to MVAC in 2000

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CHEMOTHERAPY AND BLADDER CANCER

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  1. CHEMOTHERAPY AND BLADDER CANCER Walter Stadler, MD, FACP University of Chicago

  2. Anatomy as a Problem

  3. One score and seven years ago… The metastatic d. problem • 1985 - MVAC first reported • 1997 - Gemcitabine first reported to have activity • GC found comparable to MVAC in 2000 • Response rates: • 50-55% CR +PR • 10% CR • OS 14 months • ~5% cured Sternberg et al., J Urol (1985) Stadler et al., JCO (1997) von der Maase et al., JCO (2000)

  4. For the Patient • Gemcitabine/cisplatin OR MVAC appropriate • Toxicities similar, but potential cardiac problems and mouth sores with MVAC • Major toxicities of both: • Low blood counts & risk for infection • Fatigue • Nausea • Neuropathy and hearing loss • Kidney damage

  5. Carboplatin instead of Cisplatin • More problems with low blood counts • Fewer kidney and neurologic problems • Probably less effective than Cisplatin • Significance in the metastatic setting debatable • Should not be used in peri-operative setting

  6. What if Initial Therapy is not Effective • No standard of care • Responses observed with paclitaxel, docetaxel, pemetrexed, etc, but not clear how meaningful these are for the patient • Clinical trial participation preferred

  7. N=317 pts • Enrolled from 1987 - 1998 • Muscle-invasive bladder cancer (stage T2 to T4a, all N0) • Primary objective: compare survival of patients treated with cystectomy alone vs treated with 3 cycles MVAC followed by cystectomy • Randomized phase III trial • Median follow-up 8.7 years (2003)

  8. Overall Survival • At five years, 57% alive in combination-therapy group, compared with 43% in cystectomy alone group (P=0.06) • --14% survival difference Grossman et al., NEJM (2003)

  9. Poor Adoption of These Data • Historical rates 5-10% • Retrospective review of patients with bladder cancer who underwent RC between 2003 and 2008 at University of Texas Southwestern: • Among 238 patients who underwent RC for bladder cancer, 145 had a preoperative clinical stage ≥T2 • Only 17% (25 of 145) received cisplatin-based neoadjuvant chemotherapy • Renal function was adequate in 97 (67%) of these patients Raj et al., Cancer (2011)

  10. Conclusions – Bladder Cancer • Peri-operative CDDP based chemotherapy improves survival • Best data in neoadjuvant setting • Underutilized • Ideal utilization rate unknown • >observed 5%; <80% • Gem/CDDP or MVAC is standard for metastatic disease • Carboplatin based therapies a reasonable option • No good standard for patients in whom initial therapy is not effective • Current standard is not good enough • I don’t want to give this talk in 20 yrs again • Clinical trial participation is key

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