Platinum-Free Combination Chemotherapy in Patients with Advanced or Metastatic Transitional Cell Carcinoma

A Phase I/II Trial of Gemcitabine, Paclitaxel, and Methotrexate

Primo N Lara, Frederick J Meyers, Lisa Y. Law, Nancy A. Dawson, Joan Houston, Ignacio Lauder, Martin J. Edelman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND. Platinum-based regimens have improved response rates and survival in patients with advanced transitional cell carcinoma (TCC) of the urothelial tract. However, the toxicities of platinum-based chemotherapy are considerable. Regimens with reduced toxicity that are applicable to a broader group of TCC patients without sacrificing activity therefore are of interest. METHODS. Because gemcitabine, paclitaxel, and methotrexate have each been reported to possess single-agent activity in this disease, the authors evaluated the tolerability and efficacy of fixed doses of paclitaxel (100 mg/m2 over 3 hours) and methotrexate (30 mg/m2) with escalating doses of gemcitabine (800-1000 mg/m2), all given on Days 1 and 8 every 21 days, in patients with previously untreated unresectable or metastatic TCC. RESULTS. Twenty-five patients were enrolled. Two patients were ineligible and were excluded from analysis. Because no dose-limiting toxicity occurred in the first 4 patients who were given gemcitabine at a dose of 800 mg/m2, the gemcitabine dose was escalated to 1000 mg/m2 in the next 21 patients. Of the 21 patients assessable for response, 6 had achieved a complete response (CR) and 6 had achieved a partial response, for an overall response rate of 57%. An additional patient was converted to a CR surgically. The median overall and progression-free survival times were 18 months and 9.2 months, respectively. Toxicity was predominantly neutropenia: Grade 3 in 9 patients (39%) and Grade 4 in 4 patients (17%) (according to the Southwest Oncology Group Toxicity Criteria, version 12/1994). One patient died of septic shock associated with febrile neutropenia after three cycles. CONCLUSIONS. The regimen of gemcitabine, paclitaxel, and methotrexate at this dose and schedule was found to possess activity in patients with locally advanced or metastatic TCC. Further studies of this regimen are warranted.

Original languageEnglish (US)
Pages (from-to)82-88
Number of pages7
JournalCancer
Volume100
Issue number1
DOIs
StatePublished - Jan 1 2004

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gemcitabine
Transitional Cell Carcinoma
Paclitaxel
Combination Drug Therapy
Platinum
Methotrexate

Keywords

  • Gemcitabine
  • Methotrexate
  • Paclitaxel
  • Transitional cell carcinoma (TCC)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Platinum-Free Combination Chemotherapy in Patients with Advanced or Metastatic Transitional Cell Carcinoma : A Phase I/II Trial of Gemcitabine, Paclitaxel, and Methotrexate. / Lara, Primo N; Meyers, Frederick J; Law, Lisa Y.; Dawson, Nancy A.; Houston, Joan; Lauder, Ignacio; Edelman, Martin J.

In: Cancer, Vol. 100, No. 1, 01.01.2004, p. 82-88.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND. Platinum-based regimens have improved response rates and survival in patients with advanced transitional cell carcinoma (TCC) of the urothelial tract. However, the toxicities of platinum-based chemotherapy are considerable. Regimens with reduced toxicity that are applicable to a broader group of TCC patients without sacrificing activity therefore are of interest. METHODS. Because gemcitabine, paclitaxel, and methotrexate have each been reported to possess single-agent activity in this disease, the authors evaluated the tolerability and efficacy of fixed doses of paclitaxel (100 mg/m2 over 3 hours) and methotrexate (30 mg/m2) with escalating doses of gemcitabine (800-1000 mg/m2), all given on Days 1 and 8 every 21 days, in patients with previously untreated unresectable or metastatic TCC. RESULTS. Twenty-five patients were enrolled. Two patients were ineligible and were excluded from analysis. Because no dose-limiting toxicity occurred in the first 4 patients who were given gemcitabine at a dose of 800 mg/m2, the gemcitabine dose was escalated to 1000 mg/m2 in the next 21 patients. Of the 21 patients assessable for response, 6 had achieved a complete response (CR) and 6 had achieved a partial response, for an overall response rate of 57{\%}. An additional patient was converted to a CR surgically. The median overall and progression-free survival times were 18 months and 9.2 months, respectively. Toxicity was predominantly neutropenia: Grade 3 in 9 patients (39{\%}) and Grade 4 in 4 patients (17{\%}) (according to the Southwest Oncology Group Toxicity Criteria, version 12/1994). One patient died of septic shock associated with febrile neutropenia after three cycles. CONCLUSIONS. The regimen of gemcitabine, paclitaxel, and methotrexate at this dose and schedule was found to possess activity in patients with locally advanced or metastatic TCC. Further studies of this regimen are warranted.",
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T2 - A Phase I/II Trial of Gemcitabine, Paclitaxel, and Methotrexate

AU - Lara, Primo N

AU - Meyers, Frederick J

AU - Law, Lisa Y.

AU - Dawson, Nancy A.

AU - Houston, Joan

AU - Lauder, Ignacio

AU - Edelman, Martin J.

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N2 - BACKGROUND. Platinum-based regimens have improved response rates and survival in patients with advanced transitional cell carcinoma (TCC) of the urothelial tract. However, the toxicities of platinum-based chemotherapy are considerable. Regimens with reduced toxicity that are applicable to a broader group of TCC patients without sacrificing activity therefore are of interest. METHODS. Because gemcitabine, paclitaxel, and methotrexate have each been reported to possess single-agent activity in this disease, the authors evaluated the tolerability and efficacy of fixed doses of paclitaxel (100 mg/m2 over 3 hours) and methotrexate (30 mg/m2) with escalating doses of gemcitabine (800-1000 mg/m2), all given on Days 1 and 8 every 21 days, in patients with previously untreated unresectable or metastatic TCC. RESULTS. Twenty-five patients were enrolled. Two patients were ineligible and were excluded from analysis. Because no dose-limiting toxicity occurred in the first 4 patients who were given gemcitabine at a dose of 800 mg/m2, the gemcitabine dose was escalated to 1000 mg/m2 in the next 21 patients. Of the 21 patients assessable for response, 6 had achieved a complete response (CR) and 6 had achieved a partial response, for an overall response rate of 57%. An additional patient was converted to a CR surgically. The median overall and progression-free survival times were 18 months and 9.2 months, respectively. Toxicity was predominantly neutropenia: Grade 3 in 9 patients (39%) and Grade 4 in 4 patients (17%) (according to the Southwest Oncology Group Toxicity Criteria, version 12/1994). One patient died of septic shock associated with febrile neutropenia after three cycles. CONCLUSIONS. The regimen of gemcitabine, paclitaxel, and methotrexate at this dose and schedule was found to possess activity in patients with locally advanced or metastatic TCC. Further studies of this regimen are warranted.

AB - BACKGROUND. Platinum-based regimens have improved response rates and survival in patients with advanced transitional cell carcinoma (TCC) of the urothelial tract. However, the toxicities of platinum-based chemotherapy are considerable. Regimens with reduced toxicity that are applicable to a broader group of TCC patients without sacrificing activity therefore are of interest. METHODS. Because gemcitabine, paclitaxel, and methotrexate have each been reported to possess single-agent activity in this disease, the authors evaluated the tolerability and efficacy of fixed doses of paclitaxel (100 mg/m2 over 3 hours) and methotrexate (30 mg/m2) with escalating doses of gemcitabine (800-1000 mg/m2), all given on Days 1 and 8 every 21 days, in patients with previously untreated unresectable or metastatic TCC. RESULTS. Twenty-five patients were enrolled. Two patients were ineligible and were excluded from analysis. Because no dose-limiting toxicity occurred in the first 4 patients who were given gemcitabine at a dose of 800 mg/m2, the gemcitabine dose was escalated to 1000 mg/m2 in the next 21 patients. Of the 21 patients assessable for response, 6 had achieved a complete response (CR) and 6 had achieved a partial response, for an overall response rate of 57%. An additional patient was converted to a CR surgically. The median overall and progression-free survival times were 18 months and 9.2 months, respectively. Toxicity was predominantly neutropenia: Grade 3 in 9 patients (39%) and Grade 4 in 4 patients (17%) (according to the Southwest Oncology Group Toxicity Criteria, version 12/1994). One patient died of septic shock associated with febrile neutropenia after three cycles. CONCLUSIONS. The regimen of gemcitabine, paclitaxel, and methotrexate at this dose and schedule was found to possess activity in patients with locally advanced or metastatic TCC. Further studies of this regimen are warranted.

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