The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

Abstract

Background. Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. Patients and Methods. Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.

Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies

“…Therefore, 139 remaining studies were further evaluated for eligibility, and 118 studies were further excluded because they were animal studies, had no survival data with the pretreatment NLR, were without sufficient data to extract the HRs and 95% confidence intervals (CIs), used a continuous variable as the cut-off value, or had overlapping patients or < 10 patients. A total of 21 studies were finally included in this pooled analysis, of which 17 studies included 11, 262 bladder cancer patients treated with RC or TURBT [15-17, 28-41] and 4 studies involved 862 mUC or uUC patients treated with systemic chemotherapy [42-45]. The flow diagram for the study selection process is depicted in Fig.…”

“…The prognostic role of the pretreatment NLR regarding RFS, PFS and disease-specific survival/cancer-specific survival (DSS/CSS) in bladder cancer patients was evaluated in 9, 7 and 9 studies, respectively. Of the 21 included studies, Hermanns’s study reported adjusted HRs and 95% CIs [29], while 3 studies reported HRs and 95% CIs derived only from a univariate analysis [42, 44, 45]; the remaining studies presented HRs and 95% CIs obtained by a multivariate analysis. With regard to the quality assessment of the included studies, the Newcastle-Ottawa Scale (NOS) scores ranged from 6 to 8.…”

“…Conducting surgery is the first choice for organ-confined bladder malignancies. Cisplatin-based systemic chemotherapy has been recommended as standard care for mUC or uUC patients, and novel agents alone or in combination are in development for patients with cisplatin-resistant mUC or uUC [42, 53, 54]. However, mUC or uUC is still an intractable disease with a poor prognosis.…”

“…However, mUC or uUC is still an intractable disease with a poor prognosis. Emerging studies have evaluated the prognostic value of the NLR in mUC or uUC patients, and there have been conflicting results [42-45]. In this context, we performed our study to evaluate the prognostic role of the pretreatment NLR in mUC or uUC patients treated with systemic chemotherapy, and the pooled result indicated that an elevated pretreatment NLR predicted worse OS in mUC or uUC patients with no significant heterogeneity among the included studies, which suggests that the pretreatment NLR is a prognostic indicator for mUC or uUC patients.…”

Salvage Systemic Therapy for Advanced Urothelial Carcinoma: On the Cusp of a Sea Change?

“…Optimal information regarding prognostic factors can help riskstratify patients, tailor monitoring strategies, and interpret and design clinical trials.The study by Bambury et al [5] also examined prognostic factors and suggests a prognostic impact for the neutrophil-lymphocyte ratio (NLR), which has been shown to be prognosticacrossmalignancies [16].Morerecently,aretrospective analysis of prospective trials externally validated the independent prognostic impact of hypoalbuminemia after controlling for the four recognized factors [17]. However, neutrophil and platelet counts, as well as NLR, could not be externally validated in this study.Thus, this five-factor salvage prognostic model (PS, Hb, liver metastasis, time from prior therapy, and hypoalbuminemia) resembles the four-factor first-line prognostic model, which includes anemia, PS, hypoalbuminemia, and visceral metastasis [18].…”