Background: Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood. Patients and Methods: Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed. Results: Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016). Conclusions: An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.

Keywords:
Chemotherapy discontinuation, Colorectal cancer, FOLFOX, Hypersensitivity, Neuropathy, Oxaliplatin
1.
Wolpin BM, Mayer RJ: Systemic treatment of colorectal cancer. Gastroenterology 2008;134:1296–1310.
2.
de Gramont A, Figer A, Seymour M, et al: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938–2947.
3.
Tournigand C, Andre T, Achille E, et al: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22:229–237.
4.
Misset JL: Oxaliplatin in practice. Br J Cancer 1998;77(suppl 4):4–7.
5.
Tournigand C, Cervantes A, Figer A, et al: OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer: a GERCOR study. J Clin Oncol 2006;24:394–400.
6.
Matsumoto S, Nishimura T, Kanai M, et al: Safety and efficacy of modified FOLFOX6 for treatment of metastatic or locally advanced colorectal cancer. A single-institution outcome study. Chemotherapy 2008;54:395–403.
7.
Tournigand C, Maindrault-Goebel F, Louvet C, et al: Severe anaphylactic reactions to oxaliplatin. Eur J Cancer 1998;34:1297–1298.
8.
Meyer L, Zuberbier T, Worm M, et al: Hypersensitivity reactions to oxaliplatin: cross-reactivity to carboplatin and the introduction of a desensitization schedule. J Clin Oncol 2002;20:1146–1147.
9.
Thomas RR, Quinn MG, Schuler B, Grem JL: Hypersensitivity and idiosyncratic reactions to oxaliplatin. Cancer 2003;97:2301–2307.
10.
Brandi G, Pantaleo MA, Galli C, et al: Hypersensitivity reactions related to oxaliplatin (OHP). Br J Cancer 2003;89:477–481.
11.
Maindrault-Goebel F, Andre T, Tournigand C, et al: Allergic-type reactions to oxaliplatin: retrospective analysis of 42 patients. Eur J Cancer 2005;41:2262–2267.
12.
Siu SW, Chan RT, Au GK: Hypersensitivity reactions to oxaliplatin: experience in a single institute. Ann Oncol 2006;17:259–261.
13.
Polyzos A, Tsavaris N, Gogas H, et al: Clinical features of hypersensitivity reactions to oxaliplatin: a 10-year experience. Oncology 2008;76:36–41.
14.
Andre T, Boni C, Mounedji-Boudiaf L, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–2351.
15.
Desrame J, Broustet H, Darodes de Tailly P, et al: Oxaliplatin-induced haemolytic anaemia. Lancet 1999;354:1179–1180.
16.
Earle CC, Chen WY, Ryan DP, Mayer RJ: Oxaliplatin-induced Evan’s syndrome. Br J Cancer 2001;84:441.
17.
Taleghani BM, Meyer O, Fontana S, et al: Oxaliplatin-induced immune pancytopenia. Transfusion 2005;45:704–708.
18.
Garufi C, Cristaudo A, Vanni B, et al: Skin testing and hypersensitivity reactions to oxaliplatin. Ann Oncol 2003;14:497–498.
19.
Leguy-Seguin V, Jolimoy G, Coudert B, et al: Diagnostic and predictive value of skin testing in platinum salt hypersensitivity. J Allergy Clin Immunol 2007;119:726–730.
20.
Pagani M, Bonadonna P, Senna GE, Antico A: Standardization of skin tests for diagnosis and prevention of hypersensitivity reactions to oxaliplatin. Int Arch Allergy Immunol 2008;145:54–57.
21.
National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm (accessed August 5, 2009).
22.
Schwartz JR, Bandera C, Bradley A, et al: Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women and Infants’ Hospital. Gynecol Oncol 2007;105:81–83.
23.
Markman M, Kennedy A, Webster K, et al: Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 1999;17:1141–1145.
24.
Maindrault-Goebel F, Tournigand C, Andre T, et al: Oxaliplatin reintroduction in patients previously treated with leucovorin, fluorouracil and oxaliplatin for metastatic colorectal cancer. Ann Oncol 2004;15:1210–1214.
25.
Kim BH, Bradley T, Tai J, Budman DR: Hypersensitivity to oxaliplatin: an investigation of incidence and risk factors, and literature review. Oncology 2009;76:231–238.
26.
Mis L, Fernando NH, Hurwitz HI, Morse MA: Successful desensitization to oxaliplatin. Ann Pharmacother 2005;39:966–969.
27.
Castells MC, Tennant NM, Sloane DE, et al: Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 2008;122:574–580.
28.
Giacchetti S, Bjarnason G, Garufi C, et al: Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol 2006;24:3562–3569.
29.
Lim KH, Huang MJ, Lin HC, et al: Hypersensitivity reactions to oxaliplatin: a case report and the success of a continuous infusional desensitization schedule. Anticancer Drugs 2004;15:605–607.
30.
Pagani M, Bonadonna P, Senna GE, Antico A: Standardization of skin tests for diagnosis and prevention of hypersensitivity reactions to oxaliplatin. Int Arch Allergy Immunol 2008;145:54–57.
© 2010 S. Karger AG, Basel
2010
Copyright / Drug Dosage / Disclaimer
Copyright: 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.
You do not currently have access to this content.