Use of Gemcitabine plus Carboplatin is Associated with Poor Outcomes in Urothelial Carcinoma Patients with Chronic Kidney Disease Stage 4-5
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Purpose This study aimed to investigate the clinical outcomes with gemcitabine-carboplatin (GCb), the standard treatment for patients with advanced urothelial carcinoma (UC) who are ineligible for cisplatin-based regimens, in advanced UC patients with a glomerular filtration rate (GFR) < 30 mL/min. Materials and Methods A retrospective cohort study involving GCb-treated advanced UC patients with GFR < 60 mL/min (n=89) was performed. Clinical outcomes were compared between subgroups with GFR < 30 mL/min and GFR ≥ 30 mL/min but < 60 mL/min. Results Most baseline characteristics were comparable between the two subgroups. Patients with GFR < 30 mL/min had a significantly lower objective response rate (12.5%) compared to those with higher GFR levels (56.7%) (p=0.004). The number of GCb cycles was significantly lower in patients with GFR < 30 mL/min (median 2 cycles) than in those with higher GFR levels (median 6 cycles) (p=0.002). Compared to those with GFR ≥ 30 mL/min but < 60 mL/min, patients with GFR < 30 mL/min showed significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.001 for both). Further stratification of patient subgroups according to their GFR (i.e., GFR ≥ 45 mL/min but < 60 mL/min vs. GFR ≥ 30 mL/min but < 45 mL/min vs. GFR < 30 mL/min) revealed significantly different PFS and OS (p < 0.001 for both). Conclusion The use of GCb is discouraged in advanced UC patients with GFR < 30 mL/min. Alternative therapeutic approaches with better efficacy are warranted for these patients.
Abstract
Purpose This study aimed to investigate the clinical outcomes with gemcitabine-carboplatin (GCb), the standard treatment for patients with advanced urothelial carcinoma (UC) who are ineligible for cisplatin-based regimens, in advanced UC patients with a glomerular filtration rate (GFR) < 30 mL/min. Materials and Methods A retrospective cohort study involving GCb-treated advanced UC patients with GFR < 60 mL/min (n=89) was performed. Clinical outcomes were compared between subgroups with GFR < 30 mL/min and GFR ≥ 30 mL/min but < 60 mL/min. Results Most baseline characteristics were comparable between the two subgroups. Patients with GFR < 30 mL/min had a significantly lower objective response rate (12.5%) compared to those with higher GFR levels (56.7%) (p=0.004). The number of GCb cycles was significantly lower in patients with GFR < 30 mL/min (median 2 cycles) than in those with higher GFR levels (median 6 cycles) (p=0.002). Compared to those with GFR ≥ 30 mL/min but < 60 mL/min, patients with GFR < 30 mL/min showed significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.001 for both). Further stratification of patient subgroups according to their GFR (i.e., GFR ≥ 45 mL/min but < 60 mL/min vs. GFR ≥ 30 mL/min but < 45 mL/min vs. GFR < 30 mL/min) revealed significantly different PFS and OS (p < 0.001 for both). Conclusion The use of GCb is discouraged in advanced UC patients with GFR < 30 mL/min. Alternative therapeutic approaches with better efficacy are warranted for these patients.
참고문헌 (20)
- Koufopoulou M, "Clinical evidence for the first-line treatment of advanced urothelial carcinoma : current paradigms and emerging treatment options", Cancer Treat Rev, 89, pp.102072~ (2020)
- von der Maase H, "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, 18, pp.3068~3077 (2000)
- von der Maase H, "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, pp.4602~4608 (2005)
- Bellmunt J, "Borealis-1 : a randomized, first-line, placebocontrolled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer", Ann Oncol, 28, pp.2481~2488 (2017)
- Galsky MD, "Treatment of patients with metastatic urothelial cancer"unfit"for cisplatin-based chemotherapy", J Clin Oncol, 29, pp.2432~2438 (2011)
- Bukhari N, "Update on the treatment of metastatic urothelial carcinoma", ScientificWorldJournal, 2018, pp.5682078~ (2018)
- De Santis M, "Randomized phase II", III trial assessing gemcitabine, carboplatin, pp.vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy : EORTC study 30986, J Clin Oncol[DOI]
- Na SY, "Chronic kidney disease in cancer patients : an independent predictor of cancer-specific mortality", Am J Nephrol, 33, pp.121~130 (2011)
- Park I, "Gemcitabine plus carboplatin versus gemcitabine plus oxaliplatin in cisplatin-unfit patients with advanced urothelial carcinoma : a randomised phase II study(COACH, KCSG GU10-16)", Eur J Cancer, 127, pp.183~190 (2020)
- Havrilesky LJ, "A review of relative dose intensity and survival in patients with metastatic solid tumors", Crit Rev Oncol Hematol, 93, pp.203~210 (2015)
- Beumer JH, "Improving carboplatin dosing based on estimated GFR", Am J Kidney Dis, 71, pp.163~165 (2018)
- "Chemotherapy nephrotoxicity and dose modification in patients with kidney impairment: conventional cytotoxic agents" (2020)[URL]
- Launay-Vacher V, "Renal insufficiency and cancer treatments", ESMO Open, 1, pp.e000091~ (2016)
- Iff S, "Reduced estimated GFR and cancer mortality", Am J Kidney Dis, 63, pp.23~30 (2014)
- Perazella MA, "Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do?", Kidney Int, 97, pp.62~74 (2020)
- Bellmunt J, "Pembrolizumab as second-line therapy for advanced urothelial carcinoma", N Engl J Med, 376, pp.1015~1026 (2017)
- Fradet Y, "Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer : results of >2 years of follow-up", Ann Oncol, 30, pp.970~976 (2019)
- Powles T, "Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma(DANUBE) : a randomised, openlabel, multicentre, phase 3 trial", Lancet Oncol, 21, pp.1574~1588 (2020)
- Galsky MD, "Atezolizumab with or without chemotherapy in metastatic urothelial cancer(IMvigor130) : a multicentre, randomised, placebo-controlled phase 3 trial", Lancet, 395, pp.1547~1557 (2020)
- Alva A, "LBA23 Pembrolizumab (P) combined with chemotherapy (C) vs C alone as first-line (1L) therapy for advanced urothelial carcinoma (UC): KEYNOTE-361", Ann Oncol, 31(Suppl 4), pp.S1155~ (2020)
