|Year : 2018 | Volume
| Issue : 3 | Page : 139-142
Chemotherapy in a patient with advanced carcinoma of the bladder with renal insufficiency
RB Nerli1, Shridhar C Ghagane2, Abhijit Musale3, Sushant Deole3, Shyam Mohan3, Neeraj S Dixit2, Murigendra B Hiremath4
1 Department of Urology, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus; KLES Kidney Foundation, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India
2 Department of Urology, KLES Kidney Foundation, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India
3 Department of Urology, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus, Belagavi, Karnataka, India
4 Department of Biotechnology and Microbiology, Karnatak University, Dharwad, Karnataka, India
|Date of Web Publication||28-Jun-2019|
Dr. R B Nerli
Department of Urology, KLE Academy of Higher Education and Research (Deemed.to.be.University), JNMC Campus, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
A large proportion of patients with high-risk bladder cancer also have renal insufficiency. These patients are not fit enough to receive cisplatin-based chemotherapy based on impaired renal function. This finding is most strikingly seen in the elderly population. We report a case of an elderly male presenting with advanced carcinoma of the bladder and renal dysfunction.
Keywords: Aged, bladder neoplasms, chemotherapy, chronic kidney disease, estimated glomerular filtration rate
|How to cite this article:|
Nerli R B, Ghagane SC, Musale A, Deole S, Mohan S, Dixit NS, Hiremath MB. Chemotherapy in a patient with advanced carcinoma of the bladder with renal insufficiency. J Sci Soc 2018;45:139-42
|How to cite this URL:|
Nerli R B, Ghagane SC, Musale A, Deole S, Mohan S, Dixit NS, Hiremath MB. Chemotherapy in a patient with advanced carcinoma of the bladder with renal insufficiency. J Sci Soc [serial online] 2018 [cited 2019 Oct 14];45:139-42. Available from: http://www.jscisociety.com/text.asp?2018/45/3/139/261666
| Introduction|| |
Radical cystectomy is the primary treatment modality for patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder. Patients with either extravesical disease or lymph node-positive status, are at high risk for disease recurrence after surgery alone. Perioperative chemotherapy has been used in an attempt to improve disease control and patient survival. The use of cisplatin-based combination neoadjuvant chemotherapy has shown a survival advantage in two large randomized trials and a meta-analysis.,,
One of the requirements to enroll patients in clinical trials exploring perioperative chemotherapy in urothelial carcinoma is the need for adequate renal function. It has long been known that a large proportion of patients with urothelial cancer have impaired renal function due to multiple factors, including medical comorbidities, age-related decline in glomerular filtration rate (GFR), and ureteral obstruction. It has never been systematically explored as to the degree to which impaired renal function limits the use of perioperative cisplatin-based chemotherapy.
A working group of medical oncologists has laid down certain criteria so as to define patients who are not eligible to receive cisplatin, which includes any of the following: the World Health Organization or the Eastern Cooperative Oncology Group (ECOG) performance status >2, creatinine clearance <60 mL/min, Grade 2 or above audiometric hearing loss, Grade 2 or above peripheral neuropathy, or a New York Heart Association Class III or higher heart failure. When cisplatin therapy is contraindicated, carboplatin has been substituted with the benefit of improved tolerability but with the cost of decreased efficacy.,
| Case Report|| |
A 72-year-old male presented to a nursing home with complaints of hematuria of 6-month duration. His hemoglobin levels were 9.4 gm%, serum creatinine was 3.97 mg%, and computed tomography showed a well-defined intraluminal mass lesion measuring 48 mm × 38 mm × 41 mm along the left lateral wall involving the left ureteric orifice. Left pelvicalyceal system and left ureter were dilated up to the bladder [Figure 1] and [Figure 2]. In view of the raised creatinine and dilated left pelvicalyceal system, the patient underwent left-sided double J stenting.
|Figure 1: Bladder is well distended and moderate wall thickness. An isoechoic mass of the dimension 6.1 cm × 5.3 cm × 5.0 cm is seen at the base of the bladder on the left side|
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|Figure 2: (a) Computed tomography showed a well-defined intraluminal mass lesion measuring 48 mm × 38 mm × 41 mm along the left lateral wall involving the left ureteric orifice. (b) Left pelvicalyceal system and left ureter were dilated up to the bladder|
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The patient was referred to our hospital for further management. The serum creatinine persisted to be high at around 3.74 mg%. The patient was prepared for surgery and underwent transurethral resection of bladder tumor. The histopathological opinion was high-grade muscle infiltrating bladder cancer. The clinical stage of the tumor was T3N0M0. The patient was unwilling for any surgical intervention. It was decided to treat the patient with chemoradiation. The patients Karnofsky Performance Score was 70%, and his creatinine clearance was 40 ml./min. Chemotherapy involved gemcitabine 1200 mg on day 1 and day 8, and dose-adjusted carboplatin 190 mg on day 1 of the cycle, and repeated every 21 days. The patient received 6 cycles of chemotherapy and 4500 rads of radiation to the involved region. The patient withstood the chemoradiation well and is on close follow-up. Serum creatinine done at the end of chemotherapy remained at 3.8 mg%.
| Discussion|| |
Bladder cancer is the most common malignancy involving the urinary system and one of the most prevalent solid tumors., Urothelial carcinoma, also referred to as TCC, is the most predominant histologic type, and it accounts for approximately 90% of all bladder cancers., Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic disease. Although response rates are high, the median survival is only approximately 14 months, whereas the 5-year survival rate is approximately 15% with current combination regimens.
Cisplatin has been the cornerstone of chemotherapy regimens for TCC. Cisplatin in combination with other antineoplastic agents has been shown to be significantly more effective than cisplatin monotherapy. The regimen consisting of methotrexate, vinblastine, doxorubicin, and cisplatin has consistently achieved overall survival (OS) of patients with advanced TCC of 12–14 months.,, Stratification according to the Karnofsky Performance Status (KPS) and site of metastases has identified a sizeable proportion of patients who will achieve long-term disease-free survival. Patients with no risk factors (KPS ≥80% and no visceral metastasis) had a median survival time of 33 months and a 33% likelihood of achieving 5-year survival. Cisplatin-based regimens are associated with significant toxicities, including renal, neurologic, myelosuppression, and ototoxicity. Taking into consideration that most patients with advanced bladder cancer are over 60 years of age, preexisting comorbidities preclude the administration of cisplatin. For the aforementioned reasons, approximately 40%–50% of patients with advanced bladder cancer would not be fit enough to receive cisplatin.
Renal dysfunction remains the most common reason for cisplatin-ineligibility. Up to 40% of patients with bladder cancer have renal impairment, defined as a creatinine clearance ≤60 ml/min, as calculated by the Cockroft–Gault formula [Table 1]. Renal insufficiency may be secondary to TCC itself, caused by ureteral blockage, prior nephrectomy or, more often, age-related decrease in the GFR. Creatinine levels that are usually related to a creatinine clearance of <60 ml/min are above 1.5 or 1.6 mg/dl. It is better to avoid cisplatin or other nephrotoxic agents whenever treating patients with renal dysfunction.
|Table 1: Formulas commonly used to estimate creatinine clearance (Cr Cl)|
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Carboplatin is the most widely studied agent in patients with TCC bladder with renal insufficiency. It has always been used in combination with other drugs as a means of overcoming intrinsic resistance to chemotherapy. A popular combination has been the use of carboplatin with gemcitabine, given the efficacy of gemcitabine as a single agent in urothelial carcinoma. Bamias et al. evaluated gemcitabine–carboplatin treatment regimen in 34 patients unfit for cisplatin in a Phase II trial. Treatment resulted in an overall response of 24% and a median OS of 9.8 months. Similarly in another study, Linardou et al. administered gemcitabine and carboplatin to 56 chemo-naive patients who were elderly or otherwise deemed unfit for cisplatin-based chemotherapy based on the same aforementioned criteria. Participants in the study had an ECOG performance status of 2–3 (46%) and/or a GFR of 50 ml/min or less (68%). The overall response rate (ORR) was 36%, with a median progression-free survival of 4.8 months and a median OS of 7.2 months. Bellmunt et al. administered the gemcitabine–carboplatin combination to 16 patients considered unfit for cisplatin-based therapy because of creatinine clearance ≤60 ml/min. The ORR was 44%, while the OS was not reported.
Paclitaxel has shown the best single-agent activity in TCC. As paclitaxel can be used at full doses even when renal function is impaired, it forms another partner of carboplatin in the treatment of these patients. The paclitaxel–carboplatin combination has shown ORRs of 21%–50%, with a median progression-free survival of 4–7 months and median OS of approximately 9 months.,,
| Conclusions|| |
TCC of the bladder is the most common malignancy involving the urinary system. Cisplatin is the mainstay of treatment in patients with advanced/metastatic disease. However, a large number of patients with TCC also have associated renal insufficiency, and are, therefore, unfit to receive such chemotherapy. Although 50% of patients with advanced TCC are unfit to receive cisplatin, there is a lack of randomized trials to define the optimal regimen for those with renal impairment. Multiple Phase II studies have demonstrated the feasibility and activity of substituting carboplatin for cisplatin in conjunction with either gemcitabine, taxanes, or multidrug regimens. In addition, biological agents that are not nephrotoxic are currently under study in this setting.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Quek ML, Stein JP, Clark PE, Daneshmand S, Miranda G, Cai J, et al.
Natural history of surgically treated bladder carcinoma with extravesical tumor extension. Cancer 2003;98:955-61.
Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis. Lancet 2003;361:1927-34.
Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: A randomised controlled trial. International collaboration of trialists. Lancet 1999;354:533-40.
Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al.
Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N
Engl J Med 2003;349:859-66.
Rosenberg JE, Carroll PR, Small EJ. Update on chemotherapy for advanced bladder cancer. J Urol 2005;174:14-20.
Galsky MD, Hahn NM, Rosenberg J, Sonpavde G, Hutson T, Oh WK, et al.
Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol 2011;29:2432-8.
Petrioli R, Frediani B, Manganelli A, Barbanti G, De Capua B, De Lauretis A, et al.
Comparison between a cisplatin-containing regimen and a carboplatin-containing regimen for recurrent or metastatic bladder cancer patients. A randomized phase II study. Cancer 1996;77:344-51.
Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, et al.
Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: Results of a randomized phase 2 trial. Eur Urol 2007;52:134-41.
Nerli RB, Ghagane SC, Shankar K, Sanikop AC, Hiremath MB, Dixit NS, et al.
Low-grade, multiple, ta non-muscle-invasive bladder tumors: Tumor recurrence and worsening progression. Indian J Surg Oncol 2018;9:157-61.
Nerli RB, Magdum PV, Patil AY, Devraju S, Hiremath MB. Pheochromocytoma of the urinary bladder – A case report of an unusual presentation. Indian J Surg Oncol 2015;6:303-6.
Montie JE, Bahnson RR, Cohen SM, Drucker B, Eisenberger MA, El-Galley R, et al
. Bladder cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Ne 2005;3:4-5.
von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al.
Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23:4602-8.
Bamias A, Aravantinos G, Deliveliotis C, Bafaloukos D, Kalofonos C, Xiros N, et al.
Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: A multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. J Clin Oncol 2004;22:220-8.
Sternberg CN, de Mulder PH, Schornagel JH, Théodore C, Fossa SD, van Oosterom AT, et al.
Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no 30924. J Clin Oncol 2001;19:2638-46.
von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al
. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;17:3068-77.
Vaughn DJ. Chemotherapeutic options for cisplatin-ineligible patients with advanced carcinoma of the urothelium. Cancer Treat Rev 2008;34:328-38.
Dash A, Galsky MD, Vickers AJ, Serio AM, Koppie TM, Dalbagni G, et al.
Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer 2006;107:506-13.
Bamias A, Lainakis G, Kastritis E, Antoniou N, Alivizatos G, Koureas A, et al.
Biweekly carboplatin/gemcitabine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: Report of efficacy, quality of life and geriatric assessment. Oncology 2007;73:290-7.
Linardou H, Aravantinos G, Efstathiou E, Kalofonos C, Anagnostopoulos A, Deliveliotis C, et al.
Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: Phase II study of the Hellenic Co-Operative Oncology Group. Urology 2004;64:479-84.
Bellmunt J, de Wit R, Albanell J, Baselga J. A feasibility study of carboplatin with fixed dose of gemcitabine in “unfit” patients with advanced bladder cancer. Eur J Cancer 2001;37:2212-5.
Roth BJ, Dreicer R, Einhorn LH, Neuberg D, Johnson DH, Smith JL, et al.
Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: A phase II trial of the Eastern Cooperative Oncology Group. J Clin Oncol 1994;12:2264-70.
Small EJ, Lew D, Redman BG, Petrylak DP, Hammond N, Gross HM, et al.
Southwest oncology group study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: The importance of survival as a clinical trial end point. J Clin Oncol 2000;18:2537-44.
Rajendra BN, Pingale ND, Ghagane SC, Wagh AT, Malur PR. A series of primary signet ring cell carcinoma of the urinary bladder. Indian J Surg Oncol 2017;8:443-6.
Nerli RB, Ghagane SC, Ram P, Shimikore SS, Vinchurkar K, Hiremath MB. Bladder invasion in patients with advanced colorectal carcinoma. Indian J Surg Oncol 2018;9:547-51.
[Figure 1], [Figure 2]