Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (44)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by van Moorsel, C.J.A.
Right arrow Articles by Peters, G.J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Moorsel, C.J.A.
Right arrow Articles by Peters, G.J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Annals of Oncology 10:441-448, 1999
© 1999 European Society for Medical Oncology

research-article

Pharmacokinetic schedule finding study of the combination of gemcitabine and cisplatin in patients with solid tumors

C.J.A. van Moorsel1, J.R. Kroep1, H.M. Pinedo1, G. Veerman1, D.A. Voorn1, P.E. Postmus2, J. B. Vermorken3, C.J. van Groeningen1, W.J.F. van der Vijgh1 and G.J. Peters1,

1Department of Medical Oncology, University Hospital Vrije Universiteit Amsterdam
2Department of Pulmonology, University Hospital VU The Netherlands
3Department of Oncology, University Hospital Antwerp Belgium

Correspondence to: G.J. Peters, MD. University Hospital Vrije Universiteit, Department of Medical Oncology, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: gj.peters{at}azvu.nl

Purpose: To determine possible schedule dependent pharmacokinetic and pharmacodynamic interactions between gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and cisplatin (cis-diammine-dichloroplatinum, CDDP) in patients with advanced stage solid tumors in a phase I trial.

Patients and methods: A total of 33 patients with advanced stage solid tumors were treated with gemcitabine (30-min infusion, 800 mg/m2) and cisplatin (one-hour infusion, 50 mg/m2). Sixteen patients had a four-hour interval between gemcitabine (days 1, 8, 15) and cisplatin (days 1 and 8), followed by the reverse schedule and seventeen patients had a 24-hour interval between gemcitabine (days 1,8, 15) and cisplatin (days 2 and 9), followed by the reverse schedule. Gemcitabine and cisplatin pharmacokinetics were measured in plasma and white blood cells (WBC), isolated from blood samples taken at several time points after the start of treatment.

Results: A four-hour time interval between both agents did not reveal major differences in plasma pharmacokinetics of gemcitabine, dFdU (deaminated gemcitabine) and platinum (Pt), and of gemcitabine-triphosphate (dFdCTP) accumulation and Pt-DNA adduct formation in WBC between the two different sequences of gemcitabine and cisplatin. In the patients treated with the 24-hour interval, cisplatin before gemcitabine did not significantly change peak gemcitabine levels and the AUC of plasma dFdU, but tended to increase dFdCTP AUC in WBC 1.5-fold (P < 0.06). Gemcitabine before cisplatin decreased the plasma AUC of Pt 2.1-fold (P= 0.03). No significant differences in Pt-DNA adduct levels in WBC were found, although gemcitabine before cisplatin tended to increase the 24-hour retention of Pt-DNA adducts. Creatinine clearance on day 28 was related to the peak plasma levels of total Pt (linear regression coefficient (r) = 0.47, P = 0.02, n = 26). Furthermore, the increase in the Pt-GG to Pt-AG ratio 24 hours after cisplatin treatment was related to the overall response of patients (r = 0.89, P <0.01, n = 8).

Conclusions: Of all schedules the treatment of patients with cisplatin 24 hours before gemcitabine led to the highest dFdCTP accumulation in WBC and total Pt levels in plasma. These characteristics formed the basis for further investigation of this schedule in a phase II clinical study.

cisplatin, dFdCTP accumulation, gemcitabine, pharmacodynamics, pharmacokinetics, phase I study, Pt-DNA adducts


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JCOHome page
H. K. Chew, J. H. Doroshow, P. Frankel, K. A. Margolin, G. Somlo, H.-J. Lenz, M. Gordon, W. Zhang, D. Yang, C. Russell, et al.
Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer
J. Clin. Oncol., May 1, 2009; 27(13): 2163 - 2169.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. Ceresa, E. Giovannetti, J. Voortman, A. C. Laan, R. Honeywell, G. Giaccone, and G. J. Peters
Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells
Mol. Cancer Ther., May 1, 2009; 8(5): 1026 - 1036.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J. Sigmond, R. J. Honeywell, T. J. Postma, C. M. F. Dirven, S. M. de Lange, K. van der Born, A. C. Laan, J. C. A. Baayen, C. J. Van Groeningen, A. M. Bergman, et al.
Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer
Ann. Onc., January 1, 2009; 20(1): 182 - 187.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. A. Veltkamp, R. S. Jansen, S. Callies, D. Pluim, C. M. Visseren-Grul, H. Rosing, S. Kloeker-Rhoades, V. A.M. Andre, J. H. Beijnen, C. A. Slapak, et al.
Oral Administration of Gemcitabine in Patients with Refractory Tumors: A Clinical and Pharmacologic Study
Clin. Cancer Res., June 1, 2008; 14(11): 3477 - 3486.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Voortman, E. F. Smit, R. Honeywell, B. C. Kuenen, G. J. Peters, H. van de Velde, and G. Giaccone
A Parallel Dose-Escalation Study of Weekly and Twice-Weekly Bortezomib in Combination with Gemcitabine and Cisplatin in the First-Line Treatment of Patients with Advanced Solid Tumors
Clin. Cancer Res., June 15, 2007; 13(12): 3642 - 3651.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. P.H. Wittgen, P. W.A. Kunst, K. van der Born, A. W. van Wijk, W. Perkins, F. G. Pilkiewicz, R. Perez-Soler, S. Nicholson, G. J. Peters, and P. E. Postmus
Phase I Study of Aerosolized SLIT Cisplatin in the Treatment of Patients with Carcinoma of the Lung
Clin. Cancer Res., April 15, 2007; 13(8): 2414 - 2421.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
S. M. De Lange, C. J. van Groeningen, J. R. Kroep, A. Van Bochove, J. F. Snijders, G. J. Peters, H. M. Pinedo, and G. Giaccone
Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer
Ann. Onc., March 1, 2004; 15(3): 484 - 488.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J. R. Kroep, H. M. Pinedo, G. Giaccone, A. Van Bochove, G. J. Peters, and C. J. Van Groeningen
Phase II study of cisplatin preceding gemcitabine in patients with advanced oesophageal cancer
Ann. Onc., February 1, 2004; 15(2): 230 - 235.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
B. P. Van Putte, J. M. H. Hendriks, S. Romijn, B. Pauwels, G. De Boeck, G. Guetens, E. De Bruijn, and P. E. Y. Van Schil
Pharmacokinetics after pulmonary artery perfusion with gemcitabine
Ann. Thorac. Surg., October 1, 2003; 76(4): 1036 - 1040.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Crul, N. E. Schoemaker, D. Pluim, M. Maliepaard, R. W. M. Underberg, M. Schot, R. W. Sparidans, P. Baas, J. H. Beijnen, N. van Zandwijk, et al.
Randomized Phase I Clinical and Pharmacologic Study of Weekly versus Twice-Weekly Dose-intensive Cisplatin and Gemcitabine in Patients with Advanced Non-Small Cell Lung Cancer
Clin. Cancer Res., September 1, 2003; 9(10): 3526 - 3533.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
S. Cascinu, R. Labianca, V. Catalano, S. Barni, F. Ferrau, G. D. Beretta, L. Frontini, P. Foa, G. Pancera, D. Priolo, et al.
Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)
Ann. Onc., February 1, 2003; 14(2): 205 - 208.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
B. C. Kuenen, L. Rosen, E. F. Smit, M. R.N. Parson, M. Levi, R. Ruijter, H. Huisman, M. A. Kedde, P. Noordhuis, W. J.F. van der Vijgh, et al.
Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients With Solid Tumors
J. Clin. Oncol., March 15, 2002; 20(6): 1657 - 1667.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
P. Kozuch, M. L. Grossbard, A. Barzdins, M. Araneo, A. Robin, D. Frager, P. Homel, J. Marino, P. DeGregorio, and H.W. Bruckner
Irinotecan Combined with Gemcitabine, 5-Fluorouracil, Leucovorin, and Cisplatin (G-FLIP) is an Effective and Noncrossresistant Treatment for Chemotherapy Refractory Metastatic Pancreatic Cancer
Oncologist, December 1, 2001; 6(6): 488 - 495.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. R. Kroep, G. Giaccone, D. A. Voorn, E. F. Smit, J. H. Beijnen, H. Rosing, C. J.A. van Moorsel, C. J. van Groeningen, P. E. Postmus, H. M. Pinedo, et al.
Gemcitabine and Paclitaxel: Pharmacokinetic and Pharmacodynamic Interactions in Patients With Non-Small-Cell Lung Cancer
J. Clin. Oncol., July 1, 1999; 17(7): 2190 - 2190.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.