A Phase I Clinical Trial of Irinotecan and Carboplatin in Patients with Extensive Stage Small Cell Lung CancerCrabb S.J.a, b · Bradbury J.a · Nolan L.a · Selman D.b · Muthuramalingam S.R.c · Cave J.a · Johnson P.W.M.a, b · Ottensmeier C.a, b
aDepartment of Medical Oncology, University Hospital Southampton NHS Foundation Trust, and bCancer Research UK Centre, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, and cDepartment of Medical Oncology, Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Portsmouth, UK
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: Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination. Methods: Twenty patients with extensive stage SCLC received intravenous carboplatin at an area under the curve (AUC) of 5 on day 1, and irinotecan in 40–70 mg/m2 dose levels on days 1 and 8, every 21 days, for up to 6 cycles. Results: Dose-limiting toxicity occurred in 1 patient at the 50 mg/m2 irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m2 (grade 5 neutropenic sepsis; combined grade 4 febrile neutropenia, grade 4 diarrhoea and grade 3 thrombosis). Toxicity patterns were consistent with the expected profile for this combination. The objective response rate was 75% and the median survival was 9.3 months (95% confidence interval 7.5–11.2). Conclusion: Irinotecan 60 mg/m2 on days 1 and 8 combined with carboplatin AUC 5 every 21 days is recommended for phase II evaluation. This regimen has clinical activity, acceptable toxicity and greater dose intensity over those currently tested in phase III trials.
© 2012 S. Karger AG, Basel
Rodriguez E, Lilenbaum RC: Small cell lung cancer: past, present, and future. Curr Oncol Rep 2010;12:327–334.
- Chute JP, Chen T, Feigal E, Simon R, Johnson BE: Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol 1999;17:1794–1801.
- Sambrook RJ, Girling DJ: A national survey of the chemotherapy regimens used to treat small cell lung cancer (SCLC) in the United Kingdom. Br J Cancer 2001;84:1447–1452.
- Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N: Randomised phase III trial of carboplatin plus etoposide vs. split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer 2007;97:162–169.
- Kosmidis PA, Samantas E, Fountzilas G, Pavlidis N, Apostolopoulou F, Skarlos D: Cisplatin/etoposide versus carboplatin/etoposide chemotherapy and irradiation in small cell lung cancer: a randomized phase III study – Hellenic Cooperative Oncology Group for Lung Cancer Trials. Semin Oncol 1994;21:23–30.
- Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004;22:1382–1388.
- Rouits E, Boisdron-Celle M, Dumont A, Guerin O, Morel A, Gamelin E: Relevance of different UT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Clin Cancer Res 2004;10:5151–5159.
- Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N: Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002;346:85–91.
- Lara PN, Jr., Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR: Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol 2009;27:2530–2535.
- Hanna N, Bunn PA, Jr., Langer C, Einhorn L, Guthrie T, Jr., Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A: Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 2006;24:2038–2043.
- Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M: A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol 2010;21:1810–1816.
- Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrom S, Thaning L, Vilsvik J, Aasebo U, Sorenson S: Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol 2008;26:4261–4267.
- Gandara DR, Lara PN, Jr., Natale R, Belani C: Progress in small-cell lung cancer: the lowest common denominator. J Clin Oncol 2008;26:4236–4238.
- Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: 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.
- Al-Dasooqi N, Bowen JM, Gibson RJ, Logan RM, Stringer AM, Keefe DM: Selection of housekeeping genes for gene expression studies in a rat model of irinotecan-induced mucositis. Chemotherapy 2011;57:43–53.
- Wallin AP, Francis P, Nilbert M, Svanvik J, Sun XF: Gene expression profile of colon cancer cell lines treated with SN-38. Chemotherapy 2010;56:17–25.
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.