Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma

C. Bengala, V. Guarneri, E. Giovannetti, M. Lencioni, E. Fontana, V. Mey, A. Fontana, U. Boggi, M. Del Chiaro, R. Danesi, S. Ricci, F. Mosca, M. Del Tacca, P. F. Conte

Research output: Contribution to journalArticle

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Abstract

This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate (FDR) of gemcitabine (2′-2′-difluorodeoxycitidine) infusion with circulating haemopoietic progenitor support and to evaluate the activity of the treatment. Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina (dFdU) measured at first course and the activity and expression profile of cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced pancreatic carcinoma received escalating dose of gemcitabine 10 mg m-2min-1 every 2 weeks with circulating haemopoietic progenitor support. First dose level was 3000 mg m-2 and the doses were increased by 500 mg m-2 until MTD. In all, 23 patients were enrolled. Toxicities were mild or moderate; the only patient treated at 7000 mg m-2 died because of toxicity; therefore; the MTD was established at 6500 mg m-2. The overall response rate was 22.2%. The AUC of gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a plateau at 4500 mg m-2. A significant relationship was found between the AUC of dFdU and CdA expression and activity (P <0.05). Moreover, progression rate and survival were significantly related to CdA expression and activity levels. The activity of high-dose gemcitabine is not superior to that reported with less intensive FDR schedules. The predictive role of CdA expression and activity on outcome deserves further investigation.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalBritish Journal of Cancer
Volume93
Issue number1
DOIs
Publication statusPublished - Jul 11 2005

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gemcitabine
Cytidine Deaminase
Adenocarcinoma
Maximum Tolerated Dose
Area Under Curve
Appointments and Schedules
Survival Rate
Pharmacokinetics

Keywords

  • Cytidine deaminase
  • Fixed dose rate infusion
  • Gemcitabine pharmacokinetic
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma. / Bengala, C.; Guarneri, V.; Giovannetti, E.; Lencioni, M.; Fontana, E.; Mey, V.; Fontana, A.; Boggi, U.; Del Chiaro, M.; Danesi, R.; Ricci, S.; Mosca, F.; Del Tacca, M.; Conte, P. F.

In: British Journal of Cancer, Vol. 93, No. 1, 11.07.2005, p. 35-40.

Research output: Contribution to journalArticle

Bengala, C, Guarneri, V, Giovannetti, E, Lencioni, M, Fontana, E, Mey, V, Fontana, A, Boggi, U, Del Chiaro, M, Danesi, R, Ricci, S, Mosca, F, Del Tacca, M & Conte, PF 2005, 'Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma', British Journal of Cancer, vol. 93, no. 1, pp. 35-40. https://doi.org/10.1038/sj.bjc.6602673
Bengala, C. ; Guarneri, V. ; Giovannetti, E. ; Lencioni, M. ; Fontana, E. ; Mey, V. ; Fontana, A. ; Boggi, U. ; Del Chiaro, M. ; Danesi, R. ; Ricci, S. ; Mosca, F. ; Del Tacca, M. ; Conte, P. F. / Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma. In: British Journal of Cancer. 2005 ; Vol. 93, No. 1. pp. 35-40.
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AU - Giovannetti, E.

AU - Lencioni, M.

AU - Fontana, E.

AU - Mey, V.

AU - Fontana, A.

AU - Boggi, U.

AU - Del Chiaro, M.

AU - Danesi, R.

AU - Ricci, S.

AU - Mosca, F.

AU - Del Tacca, M.

AU - Conte, P. F.

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N2 - This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate (FDR) of gemcitabine (2′-2′-difluorodeoxycitidine) infusion with circulating haemopoietic progenitor support and to evaluate the activity of the treatment. Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina (dFdU) measured at first course and the activity and expression profile of cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced pancreatic carcinoma received escalating dose of gemcitabine 10 mg m-2min-1 every 2 weeks with circulating haemopoietic progenitor support. First dose level was 3000 mg m-2 and the doses were increased by 500 mg m-2 until MTD. In all, 23 patients were enrolled. Toxicities were mild or moderate; the only patient treated at 7000 mg m-2 died because of toxicity; therefore; the MTD was established at 6500 mg m-2. The overall response rate was 22.2%. The AUC of gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a plateau at 4500 mg m-2. A significant relationship was found between the AUC of dFdU and CdA expression and activity (P <0.05). Moreover, progression rate and survival were significantly related to CdA expression and activity levels. The activity of high-dose gemcitabine is not superior to that reported with less intensive FDR schedules. The predictive role of CdA expression and activity on outcome deserves further investigation.

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