Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: Results of a large phase 2 study

David J. Vaughn, Sandy Srinivas, Walter M. Stadler, Roberto Pili, Daniel Petrylak, Cora N. Sternberg, David C. Smith, Sarah Ringuette, Edwin De Wit, Virginie Pautret, Claude George

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: The activity and safety of vinflunine was evaluated in patients with locally advanced or metastatic urothelial carcinoma (UC) who developed disease progression within 12 months of platinum-containing chemotherapy. METHODS: Patients with UC were eligible if they received a prior platinum-based regimen in the neoadjuvant/adjuvant setting or as first-line treatment for advanced/metastatic disease and had developed disease progression within 12 months. Vinflunine was administered intravenously every 3 weeks. Patients with Karnofsky performance status of 80 or 90, impaired renal function, prior pelvic irradiation, or age ≥75 years received an initial dose of 280 mg/m 2, which was escalated to 320 mg/m2 in Cycle 2 if well tolerated. All other patients received an initial dose of 320 mg/m2. The primary endpoint was response rate defined by an independent response review committee (IRRC). RESULTS: Per the IRRC, 22 patients achieved a partial response, with a response rate of 15% (95% confidence interval, 9%-21%) with a median duration of response of 6.0 months. Sixty-four (42%) patients had stable disease. The median progression-free survival was 2.8 months, and the median overall survival was 8.2 months. Myelosuppression was the most frequent adverse event, with grade 3 of 4 (adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria [version 2.0] guidelines) neutropenia reported in 58% of the patients. Grade 3 of 4 febrile neutropenia occurred in 10 (7%) patients. Nonhematologic treatment-related events (grade 3 of 4) were generally manageable and included constipation (17%), asthenia/fatigue (13%), ileus (5%), and abdominal pain (5%). No cumulative toxicity was observed. CONCLUSIONS: Vinflunine demonstrates moderate activity in patients with platinum-pretreated UC. Toxicity is manageable and noncumulative.

Original languageEnglish (US)
Pages (from-to)4110-4117
Number of pages8
JournalCancer
Volume115
Issue number18
DOIs
StatePublished - Sep 15 2009

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Platinum
Carcinoma
Advisory Committees
Disease Progression
Karnofsky Performance Status
vinflunine
Asthenia
Febrile Neutropenia
National Cancer Institute (U.S.)
Ileus
Constipation
Neutropenia
Abdominal Pain
Disease-Free Survival
Fatigue
Guidelines
Confidence Intervals
Kidney
Safety
Drug Therapy

Keywords

  • Platinum-containing chemotherapy
  • Toxicity
  • Urothelial carcinoma
  • Vinflunine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vaughn, D. J., Srinivas, S., Stadler, W. M., Pili, R., Petrylak, D., Sternberg, C. N., ... George, C. (2009). Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: Results of a large phase 2 study. Cancer, 115(18), 4110-4117. https://doi.org/10.1002/cncr.24460

Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma : Results of a large phase 2 study. / Vaughn, David J.; Srinivas, Sandy; Stadler, Walter M.; Pili, Roberto; Petrylak, Daniel; Sternberg, Cora N.; Smith, David C.; Ringuette, Sarah; De Wit, Edwin; Pautret, Virginie; George, Claude.

In: Cancer, Vol. 115, No. 18, 15.09.2009, p. 4110-4117.

Research output: Contribution to journalArticle

Vaughn, DJ, Srinivas, S, Stadler, WM, Pili, R, Petrylak, D, Sternberg, CN, Smith, DC, Ringuette, S, De Wit, E, Pautret, V & George, C 2009, 'Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: Results of a large phase 2 study', Cancer, vol. 115, no. 18, pp. 4110-4117. https://doi.org/10.1002/cncr.24460
Vaughn, David J. ; Srinivas, Sandy ; Stadler, Walter M. ; Pili, Roberto ; Petrylak, Daniel ; Sternberg, Cora N. ; Smith, David C. ; Ringuette, Sarah ; De Wit, Edwin ; Pautret, Virginie ; George, Claude. / Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma : Results of a large phase 2 study. In: Cancer. 2009 ; Vol. 115, No. 18. pp. 4110-4117.
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abstract = "BACKGROUND: The activity and safety of vinflunine was evaluated in patients with locally advanced or metastatic urothelial carcinoma (UC) who developed disease progression within 12 months of platinum-containing chemotherapy. METHODS: Patients with UC were eligible if they received a prior platinum-based regimen in the neoadjuvant/adjuvant setting or as first-line treatment for advanced/metastatic disease and had developed disease progression within 12 months. Vinflunine was administered intravenously every 3 weeks. Patients with Karnofsky performance status of 80 or 90, impaired renal function, prior pelvic irradiation, or age ≥75 years received an initial dose of 280 mg/m 2, which was escalated to 320 mg/m2 in Cycle 2 if well tolerated. All other patients received an initial dose of 320 mg/m2. The primary endpoint was response rate defined by an independent response review committee (IRRC). RESULTS: Per the IRRC, 22 patients achieved a partial response, with a response rate of 15{\%} (95{\%} confidence interval, 9{\%}-21{\%}) with a median duration of response of 6.0 months. Sixty-four (42{\%}) patients had stable disease. The median progression-free survival was 2.8 months, and the median overall survival was 8.2 months. Myelosuppression was the most frequent adverse event, with grade 3 of 4 (adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria [version 2.0] guidelines) neutropenia reported in 58{\%} of the patients. Grade 3 of 4 febrile neutropenia occurred in 10 (7{\%}) patients. Nonhematologic treatment-related events (grade 3 of 4) were generally manageable and included constipation (17{\%}), asthenia/fatigue (13{\%}), ileus (5{\%}), and abdominal pain (5{\%}). No cumulative toxicity was observed. CONCLUSIONS: Vinflunine demonstrates moderate activity in patients with platinum-pretreated UC. Toxicity is manageable and noncumulative.",
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AU - Pili, Roberto

AU - Petrylak, Daniel

AU - Sternberg, Cora N.

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N2 - BACKGROUND: The activity and safety of vinflunine was evaluated in patients with locally advanced or metastatic urothelial carcinoma (UC) who developed disease progression within 12 months of platinum-containing chemotherapy. METHODS: Patients with UC were eligible if they received a prior platinum-based regimen in the neoadjuvant/adjuvant setting or as first-line treatment for advanced/metastatic disease and had developed disease progression within 12 months. Vinflunine was administered intravenously every 3 weeks. Patients with Karnofsky performance status of 80 or 90, impaired renal function, prior pelvic irradiation, or age ≥75 years received an initial dose of 280 mg/m 2, which was escalated to 320 mg/m2 in Cycle 2 if well tolerated. All other patients received an initial dose of 320 mg/m2. The primary endpoint was response rate defined by an independent response review committee (IRRC). RESULTS: Per the IRRC, 22 patients achieved a partial response, with a response rate of 15% (95% confidence interval, 9%-21%) with a median duration of response of 6.0 months. Sixty-four (42%) patients had stable disease. The median progression-free survival was 2.8 months, and the median overall survival was 8.2 months. Myelosuppression was the most frequent adverse event, with grade 3 of 4 (adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria [version 2.0] guidelines) neutropenia reported in 58% of the patients. Grade 3 of 4 febrile neutropenia occurred in 10 (7%) patients. Nonhematologic treatment-related events (grade 3 of 4) were generally manageable and included constipation (17%), asthenia/fatigue (13%), ileus (5%), and abdominal pain (5%). No cumulative toxicity was observed. CONCLUSIONS: Vinflunine demonstrates moderate activity in patients with platinum-pretreated UC. Toxicity is manageable and noncumulative.

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