CHEMOTHERAPY AND BLADDER CANCER

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

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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 - PowerPoint PPT Presentation

Transcript of CHEMOTHERAPY AND BLADDER CANCER

Page 1: CHEMOTHERAPY AND BLADDER CANCER

CHEMOTHERAPY AND BLADDER CANCER

Walter Stadler, MD, FACPUniversity of Chicago

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Anatomy as a Problem

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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)

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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

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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

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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

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• 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)

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Overall Survival

Grossman et al., NEJM (2003)

• At five years, 57% alive in combination-therapy group, compared with 43% in cystectomy alone group (P=0.06)

--14% survival difference

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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)

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Neoadjuvant Chemotherapy

Advantage Disadvantage

Clear Survival Benefit DemonstratedClinical Staging Information Must be Utilized to

Determine Patients to be Treated; Concern for Overtreatment

Patients are More Likely to Receive Intended Chemotherapy than in Post-Operative Setting Patients May be Reluctant to “Delay” Surgery

Does Not Cause Increased Operative Morbidity Non-Responding Patients are Unnecessarily Delaying Definitive Surgical Intervention

Patients are at Their Best Performance Status

Adjuvant Chemotherapy

Advantage DisadvantageFull Pathologic Staging Information Known; Allows

Best Selection of Appropriate Patients for Therapy

Survival Benefit Not Clearly Established

A Small Subset of Patients Ineligible for Cisplatin-Based Neoadjuvant Therapy Due to Poor Renal

Function May Experience Renal Function Improvement Due to Relief of Obstruction from

the Surgery Itself

Patients Less Likely to Receive Intended Chemotherapy Due to Post-Operative Performance Status, Complications

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Disadvantage With Adjuvant

Survival Benefit Not Clearly Established

Patients Less Likely to Receive Intended Chemotherapy Due to Post-Operative Performance Status, Complications

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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