Phase II Study of Docetaxel and Gefitinib as Second-Line Therapy in Gemcitabine Pretreated Patients with Advanced Pancreatic CancerBrell J.M.a · Matin K.b · Evans T.b · Volkin R.L.b · Kiefer G.J.b · Schlesselman J.J.b · Dranko S.b · Rath L.a · Schmotzer A.b · Lenzner D.b · Ramanathan R.K.b
aUniversity Hospitals Case Medical Center, Ireland Cancer Center, Cleveland, Ohio, and bUniversity of Pittsburgh Cancer Institute, Pittsburgh, Pa., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background: There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure. Methods: EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m2 on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m2. Gefitinib, 250 mg/day orally, was given continuously. Results: Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m2 (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9–5.7). Conclusion: The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.
© 2009 S. Karger AG, Basel
- Parkin DM, Bray F, Ferlay J, et al: Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.
- Burris HA 3rd, Moore MJ, Anderson J, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreatic cancer: a randomized trial. J Clin Oncol 1997;15:2403–2413.
- Van Cutsem E, Aerts R, Haustermans K, et al: Systemic treatment of pancreatic cancer. Eur J Gastroenterol Hepatol 2004;16:265–274.
- Moore MJ, Goldstein D, Hamm J, et al: Erlotinib plus gemcitabine improves survival compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960–1966.
Kore M, Chandrasecker B, Yamanaka Y, et al: Overexpression of the human epidermal growth factor receptor in human pancreatic carcinoma is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor-alpha. J Clin Oncol 1992;90:1352–1360.
- Robinson SP, Dean BJ, Petty BA: Characterization of the A431 tumor xenograft as an in vivo model for testing epidermal growth factor-receptor antagonists. Int J Oncol 1992;1:293–298.
- Ciardiello F, Caputo R, Bianco R, 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.
Funakoshi A, Okusaka T, Ishii H, et al: Phase II study of irinotecan alone in patients with metastatic pancreatic carcinoma. J Clin Oncol 2004;22:4102.
- Cartwright TH, Cohn A, Varkey JA, et al: Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol 2002;20:160–164.
- Whitehead RP, Jacobson J, Brown TD, et al: Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study. J Clin Oncol 1997;15:2414–2419.
- Ducreux M, Mitry E, Ould-Kaci M, et al: Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol 2004;15:467–473.
- Rothenberg ML, Benedetti JK, MacDonald JS, et al: Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Study Group study. Ann Oncol 2002;13:1576–1582.
- Kozuch P, Grossbard ML, Barzdins A, et al: Irinotecam combined with gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (G-FLIP) is an effective and noncrossresistant treatment for chemotherapy refractory metastatic pancreatic cancer. Oncologist 2001;6:488–495.
- Ulrich-Pur H, Raderer M, Verena G, et al: Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 2003;88:1180–1184.
- Cantore M, Rabbi C, Fiorentini G, et al: Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology 2004;67:93–97.
- Tsavaris N, Kosmas C, Skopelitis H, et al: Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer. A phase II study. Invest New Drugs 2005;23:369–375.
- Demols A, Peeters M, Polus M, et al: Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: phase II study. Br J Cancer 2006;27:481–485.
- Ignatiadis M, Polyzos A, Stathopoulos GP, et al: Multicenter phase II study of docetaxel in combination with gefitinib in gemcitabine-pretreated patients with advanced/metastatic pancreatic cancer. Oncology 2006;71:159–163.
- Reni M, Pasetto L, Aprile G, et al: Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer 2006;27:785–791.
- Boeck S, Weigang-Kohler K, Fuchs M, et al: Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial. Ann Oncol 2007;18:745–751.
- Kulke MH, Blaszkowsky LS, Ryan DP, et al: Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol 2007;25:4787–4792.
- Lenzi R, Yalcin S, Evans DB, et al: Phase II study of docetaxel in patients with pancreatic cancer previously untreated with cytotoxic chemotherapy. Cancer Invest. 2002;20:464–472.
- Manegold C, Gatzemeier U, Buchholz E, et al: A pilot trial of gefitinib in combination with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer. Clin Lung Cancer 2005;6:343–349.
- Choe MS, Chen Z, Klass CM, et al: Enhancement of docetaxel-induced cytotoxicity by blocking epidermal growth factor receptor and cyclooxygenase-2 pathways in squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13:3015–3023.
- Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–216.
Pelzer U, Kubica K, Stieler J, et al: A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study (abstract No 4508). J Clin Oncol 2008;(May 20 suppl).
- Heymach JV, Johnson BE, Prager D, et al: Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer. J Clin Oncol 2007;25:4270–4277.
- Nakachi K, Furuse J, Ishii H, Suzuki E, Yoshino M: Prognostic factors in patients with gemcitabine-refractory pancreatic cancer. Jpn J Clin Oncol 2007;37:114–120.
- Eberhard DA, Johnson BE, Amler LC, et al: Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005;23:5900–5909.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.