Multicentre EORTC study 16997

Feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers

C. Theodore, L. Geoffrois, J. B. Vermorken, F. Caponigro, W. Fiedler, P. Chollet, A. Ravaud, G. J. Peters, C. De Balincourt, D. Lacombe, P. Fumoleau

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Abstract

In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle). Dosages of gemcitabine and its metabolite dFdU were performed on day one of cycle 1 before exposure to SCH66336 and day one of cycle 2. A total of 152 cycles were administered in 33 patients (median 3, range: 1-15). No patients had severe hematological toxicity, defined as Grade 4 thrombocytopenia or febrile neutropenia. Nine partial responses and one complete response were achieved in 31 assessable patients and corresponded to an overall response rate of 32.3% [95% CI:17%-51%]. There was no influence of exposure to SCH66336 on the level of gemcitabine or dFdU in 11 assessable patients. In conclusion, a combination of SCH66336 and gemcitabine is feasible in terms of toxicity and active as second-line treatment in patients with advanced urothelial tract cancer. SCH66336 had no effect on the pharmacokinetics of gemcitabine. Randomised trials should be undertaken to clarify the role of SCH66336 in combination with gemcitabine in cancer treatment.

Original languageEnglish
Pages (from-to)1150-1157
Number of pages8
JournalEuropean Journal of Cancer
Volume41
Issue number8
DOIs
Publication statusPublished - May 2005

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gemcitabine
Salvage Therapy
Transferases
Multicenter Studies
Neoplasms
Pharmacokinetics
Drug Therapy
Febrile Neutropenia
lonafarnib
Therapeutics

Keywords

  • Bladder cancer
  • Chemotherapy
  • Farnesyl transferase inhibitor SCH66336
  • Gemcitabine
  • Signal transduction modification

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Multicentre EORTC study 16997 : Feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers. / Theodore, C.; Geoffrois, L.; Vermorken, J. B.; Caponigro, F.; Fiedler, W.; Chollet, P.; Ravaud, A.; Peters, G. J.; De Balincourt, C.; Lacombe, D.; Fumoleau, P.

In: European Journal of Cancer, Vol. 41, No. 8, 05.2005, p. 1150-1157.

Research output: Contribution to journalArticle

Theodore, C, Geoffrois, L, Vermorken, JB, Caponigro, F, Fiedler, W, Chollet, P, Ravaud, A, Peters, GJ, De Balincourt, C, Lacombe, D & Fumoleau, P 2005, 'Multicentre EORTC study 16997: Feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers', European Journal of Cancer, vol. 41, no. 8, pp. 1150-1157. https://doi.org/10.1016/j.ejca.2005.02.015
Theodore, C. ; Geoffrois, L. ; Vermorken, J. B. ; Caponigro, F. ; Fiedler, W. ; Chollet, P. ; Ravaud, A. ; Peters, G. J. ; De Balincourt, C. ; Lacombe, D. ; Fumoleau, P. / Multicentre EORTC study 16997 : Feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers. In: European Journal of Cancer. 2005 ; Vol. 41, No. 8. pp. 1150-1157.
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abstract = "In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle). Dosages of gemcitabine and its metabolite dFdU were performed on day one of cycle 1 before exposure to SCH66336 and day one of cycle 2. A total of 152 cycles were administered in 33 patients (median 3, range: 1-15). No patients had severe hematological toxicity, defined as Grade 4 thrombocytopenia or febrile neutropenia. Nine partial responses and one complete response were achieved in 31 assessable patients and corresponded to an overall response rate of 32.3{\%} [95{\%} CI:17{\%}-51{\%}]. There was no influence of exposure to SCH66336 on the level of gemcitabine or dFdU in 11 assessable patients. In conclusion, a combination of SCH66336 and gemcitabine is feasible in terms of toxicity and active as second-line treatment in patients with advanced urothelial tract cancer. SCH66336 had no effect on the pharmacokinetics of gemcitabine. Randomised trials should be undertaken to clarify the role of SCH66336 in combination with gemcitabine in cancer treatment.",
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AU - Geoffrois, L.

AU - Vermorken, J. B.

AU - Caponigro, F.

AU - Fiedler, W.

AU - Chollet, P.

AU - Ravaud, A.

AU - Peters, G. J.

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AU - Lacombe, D.

AU - Fumoleau, P.

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N2 - In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle). Dosages of gemcitabine and its metabolite dFdU were performed on day one of cycle 1 before exposure to SCH66336 and day one of cycle 2. A total of 152 cycles were administered in 33 patients (median 3, range: 1-15). No patients had severe hematological toxicity, defined as Grade 4 thrombocytopenia or febrile neutropenia. Nine partial responses and one complete response were achieved in 31 assessable patients and corresponded to an overall response rate of 32.3% [95% CI:17%-51%]. There was no influence of exposure to SCH66336 on the level of gemcitabine or dFdU in 11 assessable patients. In conclusion, a combination of SCH66336 and gemcitabine is feasible in terms of toxicity and active as second-line treatment in patients with advanced urothelial tract cancer. SCH66336 had no effect on the pharmacokinetics of gemcitabine. Randomised trials should be undertaken to clarify the role of SCH66336 in combination with gemcitabine in cancer treatment.

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