Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium

Sweeney, Christopher J.; Roth, Bruce J.; Kabbinavar, Fairooz; Vaughn, David J.; Arning, M.; Curiel, Rafael E.; Obasaju, Coleman K.; Wang, Yanping; Nicol, Steven J.; Kaufman, Donald S.

doi:10.1200/jco.2005.03.6699

Cited by 232 publications

(147 citation statements)

References 30 publications

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“…That said, even for the 34 patients in our cohort without visceral metastases, the response rate was only 7%. Similarly, 60% of patients in the Sweeney et al [6] cohort had ECOG performance status of 0 compared with 15% here. Again, however, when our data were analyzed by subgroup, the response rate was only 11% among the 19 patients with ECOG performance status 0.…”

Section: Discussionmentioning

confidence: 90%

“…Of all the patients, 33% (n 5 43) had received prior neo-adjuvant platinum-based chemotherapy (data not shown) and 95% (n 5 122) had RECIST-measurable disease at baseline (the other 7 patients were excluded from the objective response portion of the analysis). A total of 109 (84%) patients were treated at a dose of 500 mg/m 2 , which is the FDA-approved dose for use in lung cancer and which was also the dose used in the aforementioned phase II clinical trials for UC [5,6]. Using a recently published nomogram described by Pond et al [7], we calculated the expected 6-month PFS for each patient in our cohort.…”

Section: Baseline Patient Characteristicsmentioning

confidence: 99%

“…Pemetrexed (an intravenously administered antifolate antimetabolite) is commonly used based on modest activity and good tolerability reported in two single-arm phase II trials [5,6]. The first study enrolled 45 patients and reported a 28% response rate, median progression-free survival (PFS) of 2.9 months, and median OS of 9.6 months [6]. The second trial enrolled 13 patients and reported an 8% response rate, with 2 patients (15%) achieving disease control for $6 months [5].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 90%

Section: Baseline Patient Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Trials to assess nab-paclitaxel in the firstline setting against GC or in cisplatin-unfit patients could also be considered. The only other single agent with encouraging results to date is pemetrexed, with an RR of 28% and a median OS of 9.6 months, although a smaller trial did not support those results (51).…”

Section: Metastatic Urothelial Carcinomamentioning

confidence: 94%

New Directions for Biologic Targets in Urothelial Carcinoma

Richter

Sridhar

2012

Molecular Cancer Therapeutics

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Urothelial carcinoma remains an important oncologic problem with significant morbidity and mortality. This article provides an overview of the current status of treatment of urothelial carcinoma, with an update on current trials and recent American Society of Clinical Oncology abstracts. As an alternative to focusing on the metastatic setting, we take a broad look at drug development to date, as it spans from early disease to advanced disease in the context of emerging molecular data. This approach allows us to show that each stage involves key considerations based on emerging evidence regarding molecular biology, stage-specific novel endpoints, and rational patient selection that may help further trial designs in the future. Key issues, such as neoadjuvant versus adjuvant perioperative chemotherapy, approaches to salvage second-line therapy in the metastatic setting, and treatment of elderly and cisplatin-ineligible patients, are discussed. New paradigms in clinical research, including novel endpoints, upfront rational patient selection, biomarkers, and trial design, are also addressed. Mol Cancer Ther; 11(6); 1226-35. Ó2012 AACR.

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“…Further studies are planned or underway. Pemetrexed as a single agent has also demonstrated varying activity with ORRs ranging from 8 to 28% [64,65]. Currently, the NCCN guidelines list taxanes, (paclitaxel or docetaxel), gemcitabine and pemetrexed as standard options for second-line chemotherapy, with referral to clinical trials for novel agents as the preferred recommendation when applicable.…”

Section: Systemic Therapy For Metastatic Diseasementioning

confidence: 99%

Systemic Therapy for Bladder Cancer Finally Comes into a New Age

Zibelman

Plimack

2016

Future Oncol.

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Systemic therapy for bladder cancer, both localized muscle-invasive disease and metastatic disease, has seen minimal progress over the past two decades. Current approaches rely upon cytotoxic chemotherapy combinations aimed at increasing cure rates or achieving palliation and disease control, but these regimens are fraught with short-and long-term toxicities and outcomes remain suboptimal. The emergence of systemic immunotherapies that can provide durable remissions in subsets of patients with other malignancies has the potential to transform the field, and early phase trials have begun to demonstrate activity in some patients with metastatic bladder cancer. In this article, we review the current state of systemic therapy for bladder cancer and discuss the current literature and ongoing trials utilizing various immunotherapies. KEYWORDS• bladder cancerCancers of the urinary bladder are the sixth most commonly diagnosed malignancy in the USA and the most prevalent malignancy of the GI tract, with 74,000 new cases estimated from 2015 [1]. The predominant histologic subtype is urothelial carcinoma (UC), which accounts for more than 90% of diagnoses in the western world. For patients with muscle-invasive bladder cancer (MIBC) confined to the bladder and deemed surgical candidates, radical cystectomy (RC) with pelvic lymphadenectomy remains the gold standard, with bladder preservation techniques using combinations of radiation therapy (RT) and systemic therapy receiving increased attention [2][3][4][5]. Local therapy with surgery or radiation alone is suboptimal, with median overall survival (OS) ranging from 1.8 to 3.8 years and 5-year survival of only 43% after RC and less than 40% with RT, with the majority of deaths related to distant disease [6,7]. The addition of neoadjuvant chemotherapy (NAC) has significantly improved outcomes. For patients who present with metastatic disease, systemic chemotherapy with cisplatin-based regimens, long recognized as an active drug in this disease, is accepted as the standard of care. Thus, systemic therapy is an integral component of treatment for patients with UC, yet despite tremendous advances across a multitude of malignant conditions, no new therapies have entered the armamentarium in over decade. Fortunately, recent and ongoing research in the burgeoning field of cancer immunotherapy (IT) offers hope that new agents will finally demonstrate survival benefits in clinical trials. In this article, we review the definitive studies that have established the current standards of care for systemic treatment in UC, then focus on new and future trials aiming to bring the systemic treatment of UC into the IT age.For reprint orders, please contact: reprints@futuremedicine.com

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Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium

Abstract: Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.

Cited by 232 publications

References 30 publications

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

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

New Directions for Biologic Targets in Urothelial Carcinoma

Systemic Therapy for Bladder Cancer Finally Comes into a New Age

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