Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine

Cancer. 2002 Aug 15;95(4):751-7. doi: 10.1002/cncr.10762.

Abstract

Background: New chemotherapeutic agents, including paclitaxel and gemcitabine, are active in advanced bladder carcinoma, and combination regimens with these agents have shown promising results. Unlike conventional chemotherapy regimens, such as methotrexate, vinblastine, doxorubicin, and cisplatin, there are no data available on key predictive factors for response and survival with these novel agents. Since this information is needed for selection of patients for these new combinations and for stratification purposes in ongoing randomized trials, the authors aimed to study the predictive factors for response and survival to the current regimen containing cisplatin, paclitaxel, and gemcitabine.

Methods: The authors studied 56 patients with advanced urothelial tumors treated on a Phase I/II trial of paclitaxel, cisplatin, and gemcitabine (TCG) to identify pretreatment characteristics that were prognostic for survival using this novel combination. The pretreatment characteristics analyzed were age, gender, Eastern Cooperative Oncology Group performance status, histopathology (pure transitional versus other), visceral (liver, lung, or bone) metastasis, number of sites of disease, lactate dehydrogenase, and hemoglobin.

Results: The factors that were associated with a worse survival in univariate analysis were performance status > 0, presence of visceral metastasis, and more than one site of malignant disease. In a multivariate model, performance status (P = 0.044) and visceral disease (P = 0.008) showed independent statistical significance for decreased survival. Patients were then grouped based on these two independent prognostic factors. Median survival times in the groups of patients with zero, one, or two of these risk factors were 32.8 months, 17 months, and 9.6 months, respectively (P = 0.0005).

Conclusions: A pretreatment performance status > 0 and the presence of visceral metastasis have a profound impact on survival when using the TCG regimen. These two variables will be used to stratify patients in the upcoming Phase III randomized trial comparing this TGC regimen with a gemcitabine/cisplatin regimen in advanced urothelial tumors.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / mortality*
  • Carcinoma, Transitional Cell / pathology
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Paclitaxel / administration & dosage
  • Survival Analysis
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / mortality
  • Urologic Neoplasms / drug therapy*
  • Urologic Neoplasms / mortality*
  • Urothelium*

Substances

  • Deoxycytidine
  • Paclitaxel
  • Cisplatin
  • Gemcitabine