Purpose: To evaluate the efficacy and tolerance of the docetaxel/gefitinib combination as second-line treatment in patients with advanced pancreatic cancer. Patients and Methods: Twenty-six patients pretreated with gemcitabine-based chemotherapy were enrolled in the study. Docetaxel (75 mg/m2, i.v.) was administered every 3 weeks for a maximum of 6 cycles and gefitinib (250 mg/day, p.o.) was given continuously. Results: Five (19.2%) patients achieved stable disease. The median duration of disease control was 4.8 months (range 1–13.2), the median time to disease progression 2.1 months (range 1–7.3) and the median survival time 2.9 months (range 1–13.9). Grade 3/4 neutropenia was recorded in 9 (34.6%) patients, although only 1 (3.8%) developed grade 2 febrile neutropenia. One (3.8%) patient experienced grade 3 fatigue and 2 (7.7%) grade 3 diarrhea. Grade 1/2 rash was observed in 13 (50%) patients. There were no treatment-related deaths. Conclusion: The docetaxel/gefitinib combination, although safe, has no activity as salvage treatment for advanced pancreatic cancer after failure of gemcitabine-based chemotherapy.

1.
American Cancer Society. Cancer Facts and Figures 2005. http://www.cancer.org.
2.
Burris HA 3rd: Recent updates on the role of chemotherapy in pancreatic cancer. Semin Oncol 2005;32(suppl 6):S1–S3.
3.
Lutz MP, Van Cutsem E, Wagener T, Van Laethem JL, Vanhoefer U, Wils JA, et al: Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic carcinoma: randomized phase II study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group. J Clin Oncol 2005;23:9250–9256.
4.
Lopes G, Rocha Lima CM: Docetaxel in the management of advanced pancreatic cancer. Semin Oncol 2005;32(suppl 4):S10–S23.
5.
Androulakis N, Kourousis C, Dimopoulos MA, Samelis G, Kakolyris S, Tsavaris N, et al: Treatment of pancreatic cancer with docetaxel and granulocyte colony-stimulating factor: a multicenter phase II study. J Clin Oncol 1999;17:1779–1785.
6.
Okada S, Sakata Y, Matsuno S, Kurihara M, Sasaki Y, Ohashi Y, et al: Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan. Br J Cancer 1999;80:438–443.
7.
Xiong HQ, Abbruzzese JL: Epidermal growth factor receptor-targeted therapy for pancreatic cancer. Semin Oncol 2002;29(suppl 14):31–37.
8.
Xiong HQ, Rosenberg A, LoBuglio A, Schmidt W, Wolff RA, Deutsch J, et al: Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II trial. J Clin Oncol 2004;22:2610–2616.
9.
Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M: Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 1993;13:565–569.
10.
Bruns CJ, Solorzano CC, Harbison MT, Ozawa S, Tsan R, Fan D, et al: Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res 2000;60:2926–2935.
11.
Bruns CJ, Harbison MT, Davis DW, Portera CA, Tsan R, McConkey DJ, et al: Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 2000;6:1936–1948.
12.
Sirotnak FM, Zakowski MF, Miller VA, Scher HI, Kris MG: Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res 2000;6:4885–4892.
13.
Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S, et al: Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000;6:2053–2063.
14.
Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 1981;47:207–214.
15.
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1–10.
16.
Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481.
17.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht J, Gallinger S, et al: Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC[-]CTG). Proc Am Soc Clin Oncol 2005;23:1.
18.
Milella M, Gelibter A, Di CS, Bria E, Ruggeri EM, Carlini P, et al: Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma. Cancer 2004;101:133–138.
19.
Ulrich-Pur H, Raderer M, Verena KG, Schull B, Schmid K, Haider K, et al: Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 2003;88:1180–1184.
20.
Oettle H, Arnold D, Esser M, Huhn D, Riess H: Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma. Anticancer Drugs 2000;11:635–638.
21.
Androulakis N, Syrigos K, Polyzos A, Aravantinos G, Stathopoulos GP, Ziras N, et al: Oxaliplatin for pretreated patients with advanced or metastatic pancreatic cancer: a multicenter phase II study. Cancer Invest 2005;23:9–12.
22.
Klapdor R, Fenner C: Irinotecan (Campto R): efficacy as third/forth line therapy in advanced pancreatic cancer. Anticancer Res 2000;20:5209–5212.
23.
Morelli MP, Cascone T, Troiani T, De VF, Orditura M, Laus G, et al: Sequence-dependent antiproliferative effects of cytotoxic drugs and epidermal growth factor receptor inhibitors. Ann Oncol 2005;16(suppl 4):iv61–iv68.
24.
Bell DW, Lynch TJ, Haserlat SM, Harris PL, Okimoto RA, Brannigan BW, et al: Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005;23:8081–8092.
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