Bladder Cancer Medication

  • Author: Gary David Steinberg, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS   more...
 
Updated: Feb 21, 2012
 

Medication Summary

Methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC) is the standard treatment for metastatic bladder cancer. No proven role exists for adjuvant chemotherapy. MVAC has substantial toxicity, which must be weighed against the expected benefit. The major dose-limiting toxicity is myelosuppression.

The new combination regimens show response rates and median survival comparable to MVAC but with less toxicity. Gemcitabine plus cisplatin is now considered a first-line treatment for bladder cancer.

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Antineoplastic Agents

Class Summary

These agents inhibit cell growth and proliferation.

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Methotrexate

 

Methotrexate inhibits dihydrofolate reductase (DHFR), causing a block in the reduction of dihydrofolate to tetrahydrofolate. This inhibits the formation of thymidylate and purines and arrests DNA, RNA, and protein synthesis.

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Vinblastine

 

A vinca alkaloid with cytotoxic effect via mitotic arrest, Vinblastine binds to a specific site on tubulin, prevents polymerization of tubulin dimers, and inhibits microtubule formation. Intrathecal (IT) administration may result in death.

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Doxorubicin (Adriamycin)

 

Doxorubicin is an anthracycline antibiotic that causes DNA strand breakage through effects on topoisomerase II and direct intercalation into DNA, which causes DNA polymerase inhibition. This drug is both mutagenic and carcinogenic.

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Cisplatin

 

Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. The platinum complex also can bind to nucleus and cytoplasmic protein.

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Gemcitabine (Gemzar)

 

Gemcitabine is a cytidine analog. After intracellular metabolism to its active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA.

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Contributor Information and Disclosures
Author

Gary David Steinberg, MD, FACS  The Bruce and Beth White Family Professor and Vice Chairman of Urology, Director of Urologic Oncology, Section of Urology, Department of Surgery, The University of Chicago Medical Center and Cancer Center

Gary David Steinberg, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Urological Association, Société Internationale d'Urologie (International Society of Urology), Society of Laparoendoscopic Surgeons, and Society of Urologic Oncology

Disclosure: Predictive Biosciences Consulting fee Consulting; Abbott Molecular Consulting fee Consulting; Endo Pharmaceuticals Consulting fee Consulting; Bioniche Consulting fee Consulting; Tengion Consulting fee Consulting; Archimedes Consulting fee Review panel membership

Coauthor(s)

Stanley A Brosman, MD  Clinical Professor, Department of Urology, University of California at Los Angeles Medical School

Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for Cancer Research, American Association for the Advancement of Science, American College of Surgeons, American Medical Association, American Society of Clinical Oncology, American Urological Association, Association of Clinical Research Professionals, International Society of Urological Pathology, Société Internationale d'Urologie (International Society of Urology), Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, and Western Section American Urological Association

Disclosure: Nothing to disclose.

Brendan Curti, MD  Director, Genitourinary Oncology Research, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center

Brendan Curti, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, Oregon Medical Association, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Bagi RP Jana, MD  Assistant Professor, University of Texas Medical Branch, Galveston, TX

Bagi RP Jana, MD is a member of the following medical societies: American Cancer Society, American Medical Association, American Society of Clinical Oncology, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Zhong Jiang, MD  Professor, Department of Pathology, University of Massachusetts, Memorial Medical Center

Zhong Jiang, MD is a member of the following medical societies: College of American Pathologists, International Society of Urological Pathology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

J Stephen Jones, MD, MBA, FACS  Chairman, Department of Regional Urology, Cleveland Clinic Glickman Urological and Kidney Institute; Professor of Surgery (Urology), Cleveland Clinic Lerner College of Medicine at Case Western Reserve University School of Medicine

J Stephen Jones, MD, MBA, FACS is a member of the following medical societies: Academy of Medicine Cleveland/Northern Ohio Medical Assn, American College of Surgeons, American Urological Association, International Continence Society, Society of Urologic Oncology, and Southwest Oncology Group

Disclosure: Abbott Honoraria Speaking and teaching; Cook Honoraria Consulting; HealthTronics Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; GTx Consulting fee Consulting

Mark H Katz, MD  Fellow in Urologic Oncology and Minimally Invasive Surgery, University of Chicago Medical Center

Mark H Katz, MD is a member of the following medical societies: Alpha Omega Alpha, American Urological Association, Endourological Society, and Society of Urologic Oncology

Disclosure: Nothing to disclose.

David A Levy, MD  Assistant Professor of Surgery (Urology), Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation

David A Levy, MD is a member of the following medical societies: American Association of Clinical Urologists, American Urological Association, and Society of Urologic Oncology

Disclosure: Nothing to disclose.

Di Lu, MD  Clinical Associate Professor, Department of Pathology, University of Massachusetts Medical School

Disclosure: Nothing to disclose.

Kush Sachdeva, MD  Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.

Specialty Editor Board

Martha K Terris, MD, FACS  Professor, Department of Surgery, Section of Urology, Director, Urology Residency Training Program, Medical College of Georgia; Professor, Department of Physician Assistants, Medical College of Georgia School of Allied Health; Chief, Section of Urology, Augusta Veterans Affairs Medical Center

Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Dan Theodorescu, MD, PhD  Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

Liang Cheng, MD  Professor of Pathology and Urology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Clarian Health Partners

Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, Arthur Purdy Stout Society, College of American Pathologists, International Society of Urological Pathology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Chief Editor

Bradley Fields Schwartz, DO, FACS  Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Hyung L Kim, MD, Edward M Gong, MD, and Sujeet S Acharya, MD, to the development and writing of the source articles.

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In an ileal conduit, a small segment of ileum is taken out of continuity with the gastrointestinal tract but is maintained on its mesentery. Ureters are anastomosed to one end of this ileal segment, and the other end is brought out as a stoma to the abdominal wall.
In an Indiana pouch, a urinary reservoir is created from detubularized right colon and an efferent limb of terminal ileum. Terminal ileum is plicated and brought to the abdominal wall. The continence mechanism is the ileocecal valve.
In an orthotopic neobladder, a segment of ileum is used to construct a neobladder, which is connected to the urethra. Orthotopic neobladder most closely restores the natural storage and voiding function of the native bladder.
The classic appearance of carcinoma in situ as a flat, velvety patch. However, using special staining techniques such as 5-aminolevulinic acid, it has been shown that significant areas of carcinoma in situ are easily overlooked by conventional cystoscopy. Courtesy of Abbott and Vysis Inc.
Papillary bladder tumors such as this one are typically of low stage and grade (Ta-G1). Courtesy of Abbott and Vysis Inc.
Sessile lesions as shown usually invade muscle, although occasionally a tumor is detected at the T1-G3 stage prior to muscle invasion. Courtesy of Abbott and Vysis Inc.
Photograph in which fluorescence in situ hybridization centromere staining identifies aneuploidy of chromosome 3. Multiple instances of overexpression of the chromosome (note the multiple red dots, which identify centromeres of this chromosome) prove aneuploidy.
Cross-section through the bladder, uterus, and vagina with squamous cell carcinoma of the bladder infiltrating through the bladder wall into the vaginal wall.
Table 1. Clinical Findings and Recommended Action
Cystoscopy Findings Urine Cytology Findings FISH* Findings Action
NegativeNegativeNegative†Routine follow-up
NegativeNegativePositive‡Increased frequency of surveillance, whether FISH findings are false-positive or anticipatory positive
NegativePositiveNegative or positiveCancer until proven otherwise
  • Upper tract imaging with contrast
  • Cystoscopy with retrograde pyelography, washings, and/or ureteroscopy
  • Evaluate urethra
  • Increased frequency of surveillance upon negative findings
*FISH - Fluorescent in situ hybridization.



†Negative predictive value 95%.



‡Positive predictive value 30%.



Table 2. Recurrence and Progression Rates at 5 Years for Ta, T1, and CIS TCC of the Bladder Treated With BCG
Stage Recurrence, % Progression, %
Ta5511
T16131
CIS4523
G1612-4
G2565-7
G350-7030-40
Table 3. Most Common Complications of Radical Cystectomy
Early Complications Rate, % Late Complications Rate, %
Ileus10Small-bowel obstruction7.4
Wound infection5.5Ureteroenteric stricture7.0
Sepsis4.9Renal calculi3.9
Pelvic abscess4.7Acute pyelonephritis3.1
Hemorrhage3.4Parastomal hernia2.8
Wound dehiscence3.3Stomal stenosis2.8
Bowel obstruction3.0Incisional hernia2.2
Enterocutaneous fistula2.2Fistula1.3
Rectal injury2.2Rectal complications< 1
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