Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Apr;63(4):717-23.
doi: 10.1016/j.eururo.2012.11.042. Epub 2012 Nov 26.

Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials

Guru Sonpavde  1 , Gregory R Pond, Ronan Fougeray, Toni K Choueiri, Angela Q Qu, David J Vaughn, Guenter Niegisch, Peter Albers, Nicholas D James, Yu-Ning Wong, Yoo-Joung Ko, Srikala S Sridhar, Matthew D Galsky, Daniel P Petrylak, Ulka N Vaishampayan, Awais Khan, Nicholas J Vogelzang, Tomasz M Beer, Walter M Stadler, Peter H O'Donnell, Cora N Sternberg, Jonathan E Rosenberg, Joaquim Bellmunt
Affiliations

Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials

Guru Sonpavde et al. Eur Urol. 2013 Apr.

Abstract

Background: Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM).

Objectives: The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors.

Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n=570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n=352).

Outcome measurements and statistical analysis: Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures.

Results and limitations: ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic=0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable.

Conclusions: Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Likelihood ratio χ2 statistics. The optimal discriminatory ability, measured by the likelihood ratio χ2-statistic, occurred when the cut-off point was 3 mo for all patients and those who received prior chemotherapy for metastatic disease. For nonmetastatic disease, the optimal cut-off point was 10 mo.
Fig. 2
Fig. 2
Survival based on time from prior chemotherapy.
Fig. 3
Fig. 3
Survival based on number of risk factors.
See this image and copyright information in PMC

References

    1. Sonpavde G, Sternberg CN, Rosenberg JE, Hahn NM, Galsky MD, Vogelzang NJ. Second-line systemic therapy and emerging drugs for metastatic transitional-cell carcinoma of the urothelium. Lancet Oncol. 2010;11:861–870. - PubMed
    1. Albers P, Park SI, Niegisch G, et al. Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99] Ann Oncol. 2011;22:288–294. - PubMed
    1. Beer TM, Goldman B, Nichols CR, et al. Southwest Oncology Group phase II study of irinotecan in patients with advanced transitional cell carcinoma of the urothelium that progressed after platinumbased chemotherapy. Clin Genitourin Cancer. 2008;6:36–39. - PubMed
    1. Choueiri TK, Ross RW, Jacobus S, et al. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol. 2012;30:507–512. - PMC - PubMed
    1. Culine S, Theodore C, De Santis M, et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer. 2006;94:1395–1401. - PMC - PubMed

LinkOut - more resources