Prognostic Factors for Survival With Gemcitabine Plus 5-fluorouracil Based Regimens for Metastatic Renal Cancer
Abstract
Purpose:
Combination gemcitabine and 5-fluorouracil (5-FU) may have activity in metastatic renal cell cancer. To identify patient subgroups most likely to benefit and compare survival to that in previously described patient series long-term survival as a function of known and suspected prognostic variables was determined.
Materials and Methods:
The survival status of 153 patients with metastatic renal cell cancer treated on 1 phase I and 4 phase II trials of gemcitabine/5-FU based regimens was updated. Univariate and multivariate Cox proportional hazards models were constructed using multiple imputation for missing values.
Results:
Performance status, prior nephrectomy, number of metastatic sites, decreased albumin and elevated alkaline phosphatase were highly prognostic for survival. Sarcomatoid differentiation and hypercalcemia had borderline prognostic significance. Using a previous described prognostic model that divided patients into 3 risk groups survival in those treated with gemcitabine/5-FU in this series was consistently better than survival in similar patients treated in the Motzer series.
Conclusions:
Previously described prognostic factors for survival in metastatic renal cancer were confirmed. There is no clearly identifiable group that is most likely to benefit from a gemcitabine/5-FU regimen but there is a continued suggestion that this regimen provides a modest improvement over historical chemotherapy approaches.
References
- 1 : Systemic therapy for renal cell carcinoma. J Urol2000; 163: 408. Link, Google Scholar
- 2 : A randomized double-blind placebo-controlled trial of bevacizumab (anti-VEGF antibody) demonstrating a prolongation in time to progression in patients with metastatic renal cancer. Proc Amer Soc Clin Oncol2002; 21: 5a. Google Scholar
- 3 : Phase I study to evaluate multiple regimens of intravenous 5-fluorouracil administered in combination with weekly gemcitabine in patients with advanced solid tumors: a potential broadly active regimen for advanced solid tumor malignancies. Cancer2001; 92: 1567. Google Scholar
- 4 : Phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil in patients with metastatic renal cell cancer. J Clin Oncol2000; 18: 2419. Google Scholar
- 5 : A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with metastatic renal cell carcinoma. Cancer2002; 94: 2602. Google Scholar
- 6 : A phase II trial of weekly intravenous gemcitabine and cisplatin with continuous infusion fluorouracil in patients with metastatic renal cell carcinoma. Ann Oncol2002; 13: 116. Google Scholar
- 7 : A high rate of venous thromboembolism in a multi-institutional phase II trial of weekly intravenous gemcitabine with continuous infusion fluorouracil and daily thalidomide in patients with metastatic renal cell carcinoma. Cancer2002; 95: 1629. Google Scholar
- 8 : New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst2000; 92: 205. Google Scholar
- 9 : Regression models and life tables. J R Stat Soc Series B1972; 34: 187. Google Scholar
- 10 : Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol1999; 17: 2530. Google Scholar
- 11 : Multiple Imputation for Nonresponse in Surveys. New York: John Wiley1987. Google Scholar
- 12 : Analysis of Incomplete Multivariate Data. London: Chapman & Hall1997. Google Scholar
- 13 : Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. J Clin Oncol2000; 18: 1928. Google Scholar
- 14 : Nonparametric estimation from incomplete observations. J Am Stat Assoc1958; 53: 457. Google Scholar
- 15 : A confidence interval for the median survival time. Biometrics1982; 38: 29. Google Scholar
- 16 : Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d'Immunotherapie. Ann Oncol2002; 13: 1460. Google Scholar
- 17 : Prognostic factors for survival in patients with recurrent or metastatic renal cell carcinoma. Cancer Res1988; 48: 7310. Google Scholar
- 18 : Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol2001; 19: 1649. Google Scholar
- 19 : Expanding the indications for surgery and adjuvant interleukin-2-based immunotherapy in patients with advanced renal cell carcinoma. Cancer J Sci Am2000; 6: S88. Google Scholar
- 20 : Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med2001; 345: 1655. Google Scholar
From the Section of Hematology/Oncology (WMS, CG, CWR, TMZ, NJV), and Departments of Health Sciences (DH, TK) and Pathology (XY), University of Chicago, Chicago, Illinois
