Top

Cancer Chemotherapy and Pharmacology

Published in:

01-07-2015 | Original Article

Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma

Authors: Yi Rang Kim, Jae Lyun Lee, Dalsan You, In Gab Jeong, Cheryn Song, Bumsik Hong, Jun Hyuk Hong, Hanjong Ahn

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2015

Abstract

Purpose

Cisplatin-based chemotherapies are standard treatment regimens of advanced urothelial cell carcinoma. But a significant proportion of patients are unsuitable for cisplatin due to impaired renal function. Carboplatin-based regimens such as gemcitabine and carboplatin regimen (GCb) were applied due to less nephrotoxicity and side effects in these patients. However, it is known that clinical outcome of carboplatin-based regimens was unsatisfactory compared to cisplatin-based regimens. We compared the nephrotoxicity and response to treatment between GCb and gemcitabine plus split-dose cisplatin regimen (GC-S).

Methods

GC-S consists of cisplatin 35 mg/m² given on day 1, 2 and gemcitabine 1000 mg/m² on day 1, 8 every 3 weeks. GCb consists of carboplatin (AUC 4.5) on day 1 and gemcitabine 1000 mg/m² on day 1, 8 every 3 weeks. Patient demographics, serum creatinine and calculated GFR, adverse events, and radiologic response were retrospectively reviewed.

Results

Forty-four patients with advanced urothelial carcinoma treated with GCb (n = 22) or GC-S (n = 22) in our institution. There was no difference at deterioration of serum creatinine or GFR between GCb and GC-S (p = 0.442, p = 0.345). For patients who had GFR < 60 mL/min/1.73 m² subgroup, similar results were produced (p = 0.292, p = 0.186). In addition, GC-S (68.4 %) showed improved response compared to GCb (31.6 %) (p = 0.023). Both treatments were well tolerated, and there were no unexpected serious adverse events.

Conclusions

Based on preserved renal function, favorable response, and tolerability, GC-S could be a promising alternative to GCb for cisplatin-unfit patients with advanced urothelial carcinoma.

Available only for authorised users

Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics. CA Cancer J Clin 64(1):9–29. doi:10.3322/caac.21208 PubMedCrossRef

Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L, Group EG-UC (2006) Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer 42(1):50–54. doi:10.1016/j.ejca.2005.08.032 PubMedCrossRef

von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M (2005) 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 23(21):4602–4608. doi:10.1200/JCO.2005.07.757 PubMedCrossRef

De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Gil T, Marreaud S, Daugaard G, Skoneczna I, Collette S, Lorent J, de Wit R, Sylvester R (2012) Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 30(2):191–199. doi:10.1200/JCO.2011.37.3571 PubMedCentralPubMedCrossRef

Vaughn DJ (2008) Chemotherapeutic options for cisplatin-ineligible patients with advanced carcinoma of the urothelium. Cancer Treat Rev 34(4):328–338PubMedCrossRef

Bellmunt J, Ribas A, Eres N, Albanell J, Almanza C, Bermejo B, Sole LA, Baselga J (1997) Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma. Cancer 80(10):1966–1972PubMedCrossRef

Dogliotti L, Carteni G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L (2007) 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 52(1):134–141. doi:10.1016/j.eururo.2006.12.029 PubMedCrossRef

Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004) Meta-analysis of randomized clinical trials comparing Cisplatin to Carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22(19):3852–3859. doi:10.1200/JCO.2004.02.109 PubMedCrossRef

Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J et al (1990) A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. J Clin Oncol 8(9):1556–1562PubMed

10.

Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G (2002) Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol 13(10):1539–1549PubMedCrossRef

11.

Hussain SA, Palmer DH, Swinson DE, Riley P, Wills A, Brown C, Draycott C, El-Modir A, Peake DR, Rea DW, Chetiyawardana AD, Cullen MH (2008) A phase II clinical trial of gemcitabine and split dose cisplatin in advanced non-small cell lung cancer in an outpatient setting. Oncol Rep 20(1):233–237PubMed

12.

Hussain SA, Stocken DD, Riley P, Palmer DH, Peake DR, Geh JI, Spooner D, James ND (2004) A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer. Br J Cancer 91(5):844–849. doi:10.1038/sj.bjc.6602112 PubMedCentralPubMed

13.

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470PubMedCrossRef

14.

De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Gil T, Marreaud S, Daugaard G, Skoneczna I (2012) Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 30(2):191–199PubMedCentralPubMedCrossRef

15.

Arany I, Safirstein RL (2003) Cisplatin nephrotoxicity. Semin Nephrol 23(5):460–464PubMedCrossRef

16.

Meijer S, Mulder NH, Sleijfer DT, de Jong PE, Sluiter WJ, Schraffordt Koops H, van der Hem GK (1982) Nephrotoxicity of cis-diamminedichloride platinum (CDDP) during remission-induction and maintenance chemotherapy of testicular carcinoma. Cancer Chemother Pharmacol 8(1):27–30PubMedCrossRef

17.

Bournakis E, Dimopoulos MA, Bamias A (2011) Management of advanced bladder cancer in patients with impaired renal function. Expert Rev Anticancer Ther 11(6):931–939. doi:10.1586/era.10.197 PubMedCrossRef

18.

Pabla N, Dong Z (2008) Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 73(9):994–1007. doi:10.1038/sj.ki.5002786 PubMedCrossRef

19.

Yao X, Panichpisal K, Kurtzman N, Nugent K (2007) Cisplatin nephrotoxicity: a review. Am J Med Sci 334(2):115–124. doi:10.1097/MAJ.0b013e31812dfe1e PubMedCrossRef

20.

Bamias A, Lainakis G, Kastritis E, Antoniou N, Alivizatos G, Koureas A, Chrisofos M, Skolarikos A, Karayiotis E, Dimopoulos MA (2007) 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 73(5–6):290–297. doi:10.1159/000132394 PubMedCrossRef

21.

Bellmunt J, De Wit R, Albanell J, Baselga J (2001) A feasibility study of carboplatin with fixed dose of gemcitabine in ‘unfit’ patients with advanced bladder cancer. Eur J Cancer 37(17):2212–2215PubMedCrossRef

22.

Linardou H, Aravantinos G, Efstathiou E, Kalofonos C, Anagnostopoulos A, Deliveliotis C, Bafaloukos D, Athanasios Dimopoulos M, Bamias A, Phase IIsoHC-oOG (2004) 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 64(3):479–484. doi:10.1016/j.urology.2004.04.024 PubMedCrossRef

23.

Small EJ, Lew D, Redman BG, Petrylak DP, Hammond N, Gross HM, Eastham JA, Crawford ED (2000) 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 18(13):2537–2544PubMed

24.

Vaughn DJ, Manola J, Dreicer R, See W, Levitt R, Wilding G (2002) Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer 95(5):1022–1027. doi:10.1002/cncr.10782 PubMedCrossRef

25.

Carles J, Esteban E, Climent M, Font A, Gonzalez-Larriba JL, Berrocal A, Garcia-Ribas I, Marfa X, Fabregat X, Albanell J, Bellmunt J (2007) Gemcitabine and oxaliplatin combination: a multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer. Ann Oncol 18(8):1359–1362. doi:10.1093/annonc/mdm160 PubMedCrossRef

26.

Culine S, Flechon A, Guillot A, Le Moulec S, Pouessel D, Rolland F, Ravaud A, Houede N, Mignot L, Joly F, Oudard S, Gourgou S (2011) Gemcitabine or gemcitabine plus oxaliplatin in the first-line treatment of patients with advanced transitional cell carcinoma of the urothelium unfit for cisplatin-based chemotherapy: a randomized phase 2 study of the French Genitourinary Tumor Group (GETUG V01). Eur Urol 60(6):1251–1257. doi:10.1016/j.eururo.2011.08.072 PubMedCrossRef

27.

Dimopoulos MA, Deliveliotis C, Moulopoulos LA, Papadimitriou C, Mitropoulos D, Anagnostopoulos A, Athanassiades P, Dimopoulos C (1998) Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel. Urology 52(1):56–60PubMedCrossRef

28.

Ricci S, Galli L, Chioni A, Iannopollo M, Antonuzzo A, Francesca F, Vocaturo V, Selli C, Orlandini C, Conte P (2002) Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum-based regimens. Cancer 95(7):1444–1450. doi:10.1002/cncr.10860 PubMedCrossRef

29.

Turkolmez K, Beduk Y, Baltaci S, Gogus C, Gogus O (2003) Gemcitabine plus vinorelbine chemotherapy in patients with advanced bladder carcinoma who are medically unsuitable for or who have failed cisplatin-based chemotherapy. Eur Urol 44(6):682–686PubMedCrossRef

30.

Carles J, Suarez C, Mesia C, Nogue M, Font A, Domenech M, Suarez M, Tusquets I, Gallen M, Albanell J, Fabregat X (2006) Feasibility study of gemcitabine and cisplatin administered every two weeks in patients with advanced urothelial tumors and impaired renal function. Clin Transl Oncol 8(10):755–757PubMedCrossRef

Title: Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma
Authors: Yi Rang Kim
Jae Lyun Lee
Dalsan You
In Gab Jeong
Cheryn Song
Bumsik Hong
Jun Hyuk Hong
Hanjong Ahn
Publication date: 01-07-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2774-z

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial)

Inhibition of prostate cancer cell growth by 3′,4′,5′-trimethoxyflavonol (TMFol)

Safety, tolerability, and efficacy of oxaliplatin-based adjuvant chemotherapy after curative resection of hepatic or extrahepatic metastases of Stage IV colorectal cancer

A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck

Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia

Development of a new equation to estimate creatinine clearance in cancer patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer