Annals of Oncology 15:831-838, 2004
© 2004 European Society for Medical Oncology
Original Paper |
Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors
Received 24 September 2003; revised 12 January 2004; accepted 22 January 2004Background:
The aim of this study was to investigate the tolerability, pharmacokinetic interaction and antitumor activity of gefitinib (‘Iressa’, ZD1839), an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, combined with gemcitabine and cisplatin in chemotherapy-naïve patients with advanced solid tumors.
Patients and methods:
This was an open-label feasibility trial evaluating two doses of gefitinib (250 and 500 mg/day) in combination with gemcitabine and cisplatin. Gefitinib was administered daily from day 2 onwards. Gemcitabine 1250 mg/m2 was given on days 1 and 8 and cisplatin 80 mg/m2 on day 1 for up to six 3-week cycles. Patients could then continue to receive gefitinib monotherapy.
Results:
Eighteen patients were entered, nine at each gefitinib dose level. Two patients developed dose-limiting toxicity: one grade 3 convulsion (250 mg/day dose group) and one grade 3 rash (500 mg/day dose group). The most frequently occurring adverse events in the combination phase were vomiting (17 patients), asthenia (16), nausea (14), diarrhea (14) and skin rash (13). The most common grade 3/4 adverse events were vomiting (seven patients), asthenia (six), thrombocytopenia (six), diarrhea (five) and anorexia (five). Pharmacokinetic analyses showed no apparent pharmacokinetic interaction between gefitinib and cisplatin or gemcitabine, with the exception of a possible small increase in the geometric mean exposure to gemcitabine seen on day 8 of therapy when given alone with the higher dose of gefitinib. Of 17 evaluable patients, nine had confirmed partial responses, seven had stable disease and one had progressive disease.
Conclusions:
Combination therapy of gefitinib with cisplatin and gemcitabine had a manageable and predictable safety profile, no major effect on exposure to any of the three drugs and antitumor activity.
1 VU University Medical Center, Amsterdam, The Netherlands; 2 Hospital Clinico San Carlos, Madrid, Spain; 3 University Hospital Gasthuisberg, Leuven, Belgium; 4 AstraZeneca, Macclesfield, UK; 5 AstraZeneca, Wilmington, DE, USA
Key words: combination therapy, efficacy, gefitinib, Iressa, NSCLC, tolerability
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. P. Jani, R. S. Finn, M. Campbell, K. G. Coleman, R. D. Connell, N. Currier, E. O. Emerson, E. Floyd, S. Harriman, J. C. Kath, et al. Discovery and Pharmacologic Characterization of CP-724,714, a Selective ErbB2 Tyrosine Kinase Inhibitor Cancer Res., October 15, 2007; 67(20): 9887 - 9893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Y. Chun, F. Y. Feng, A. M. Scheurer, M. A. Davis, T. S. Lawrence, and M. K. Nyati Synergistic Effects of Gemcitabine and Gefitinib in the Treatment of Head and Neck Carcinoma Cancer Res., January 15, 2006; 66(2): 981 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tsurutani, J. Fukuoka, H. Tsurutani, J. H. Shih, S. M. Hewitt, W. D. Travis, J. Jen, and P. A. Dennis Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non-Small-Cell Lung Cancer Tumors J. Clin. Oncol., January 10, 2006; 24(2): 306 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Giaccone Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non-Small-Cell Lung Cancer J. Clin. Oncol., May 10, 2005; 23(14): 3235 - 3242. [Abstract] [Full Text] [PDF]
|
|