Top

Published in:

01-06-2017 | Original Article

The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum

Authors: Takumi Fujiwara, Hirotsugu Kenmotsu, Tateaki Naito, Takahisa Kawamura, Nobuaki Mamesaya, Mie Kotake, Haruki Kobayashi, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Tetsuhiko Taira, Haruyasu Murakami, Katsuhiro Omae, Keita Mori, Masahiro Endo, Toshiaki Takahashi

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2017

Abstract

Purpose

This study was to determine the incidence and risk factors of febrile neutropenia in chemotherapy-naïve Japanese patients treated systemically with etoposide plus platinum for lung cancer.

Methods

The study was a retrospective analysis of 244 patients who were monitored for febrile neutropenia through multiple cycles of the combination of etoposide with platinum, and the associations between incidence of febrile neutropenia and patient characteristics were evaluated.

Results

Eighty-eight patients were treated with etoposide plus cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244 patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88 (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%) patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus carboplatin. Male gender and previous radiotherapy were identified by multivariate analysis as independent risk factors for febrile neutropenia.

Conclusions

These results contrast with findings in Western patients and suggest that ethnic differences exist in the incidence of febrile neutropenia in patients receiving etoposide plus platinum chemotherapy. In addition, our results suggest that primary prophylaxis with granulocyte colony-stimulating factor should be considered for patients with these risk factors for febrile neutropenia prior to treatment with etoposide plus platinum.

Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin Oncol 63:11–30. doi:10.3322/caac.21166 CrossRef

Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24:4539–4544. doi:10.1200/JCO.2005.04.4859 CrossRefPubMed

Shepherd FA, Crowley J, Van Houtte P et al (2007) The international association for the study of lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol 2:1067–1077. doi:10.1097/JTO.0b013e31815bdc0d CrossRefPubMed

Lara PN Jr, Natale R, Crowley J et al (2009) 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 27:2530–2535. doi:10.1200/JCO.2008.20.1061 CrossRefPubMedPubMedCentral

Hanna N, Bunn PA Jr, Langer C et al (2006) 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 24:2038–2043. doi:10.1200/JCO.2005.04.8595 CrossRefPubMed

Zatloukal P, Cardenal F, Szczesna A et al (2010) 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 21:1810–1816. doi:10.1093/annonc/mdq036 CrossRefPubMed

Okamoto H, Watanabe K, Kunikane H et al (2007) 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 97:162–169. doi:10.1093/annonc/mdq036 CrossRefPubMedPubMedCentral

Ochi N, Hotta K, Takigawa N et al (2012) Treatment-related death in patients with small-cell cancer in phase III trials over the last two decades. PLoS One 7:e42798. doi:10.1371/journal.pone.0042798 CrossRefPubMedPubMedCentral

Talcott JA, Siegel RD, Finberg R et al (1992) Risk assessment in cancer patients with fever and neutropenia: a prospective, two center validation of a prediction rule. J Clin Oncol 10:316–322. doi:10.1200/JCO.1992.10.2.316 CrossRefPubMed

10.

Kuderer NM, Dale DC, Crawford J et al (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258–2266. doi:10.1002/cncr.21847 CrossRefPubMed

11.

Caggiano V, Weiss RV, Rickert TS et al (2005) Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 103:1916–1924. doi:10.1002/cncr.20983 CrossRefPubMed

12.

Smith TJ, Khatcheressian J, Lyman GH et al (2006) 2006 Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24:3187–3205. doi:10.1200/JCO.2006.06.4451 CrossRefPubMed

13.

Socinski MA, Smit EF, Lorigan P et al (2009) Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naïve patients with extensive-stage small-cell lung cancer. J Clin Oncol 27:4787–4792. doi:10.1200/JCO.2009.23.1548 CrossRefPubMed

14.

Schmittel A, Sebastian M, Fischer von Weikersthal L et al (2011) A German multicenter, randomized phase III trial comparing irinotecan–carboplatin with etoposide–carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol 22:1798–1804. doi:10.1093/annonc/mdq652 CrossRefPubMed

15.

Langer CJ, Albert I, Ross HJ et al (2014) Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer. Lung Cancer 85:420–428. doi:10.1016/j.lungcan.2014.05.003 CrossRefPubMed

16.

Sekine I, Okamoto H, Horai T et al (2014) A randomized phase III study of single-agent amrubicin vs carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer. Clin Lung Cancer 15:96–102. doi:10.1016/j.cllc.2013.11.006 CrossRefPubMed

17.

Gandara DR, Kawaguchi T, Crowley J et al (2009) Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics. J Clin Oncol 27:3540–3546. doi:10.1200/JCO.2008.20.8793 CrossRefPubMedPubMedCentral

18.

Lyman GH, Kuderer NM, Crawford J et al (2011) Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy. Cancer 117:1917–1927. doi:10.1002/cncr.25691 CrossRefPubMed

19.

Lyman GH, Delgado DJ (2003) Risk and timing of hospitalization for febrile neutropenia in patients receiving CHOP, CHOP-R, or CNOP chemotherapy for intermediate-grade non-Hodgkin lymphoma. Cancer 98:2402–2409. doi:10.1002/cncr.11827 CrossRefPubMed

20.

Salar A, Haioun C, Rossi FG et al (2012) The need for improved neutropenia risk assessment in DLBCL patients receiving R-CHOP-21: findings from clinical practice. Leuk Res 36:548–553. doi:10.1016/j.leukres.2012.02.002 CrossRefPubMed

21.

Crawford J, Caserta C, Roila F (2010) ESMO guidelines working group. Hematopoietic growth factors: ESMO clinical practice guidelines for the applications. Ann Oncol 21(suppl 5):v248–v251. doi:10.1093/annonc/mdq195 CrossRefPubMed

22.

Freifeld AG, Bow EJ, Sepkowitz KA et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52:e56–e93. doi:10.1093/cid/cir073 CrossRefPubMed

23.

Crawford J, Armitage J, Balducci L et al (2013) Myeloid growth factors. J Natl Compr Cancer Netw 11:1266–1290CrossRef

24.

Japanese Society of Medical Oncology (2015) Practical guideline of febrile neutropenia (FN), 5th edn. Nankodo Co., Ltd, Tokyo

25.

National Cancer Institute (2009) Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE). http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 16 March 2017

26.

Kenmotsu H, Tanigawara Y (2015) Pharmacokinetics, dynamics and toxicity of docetaxel: why the Japanese dose differs from the Western dose. Cancer Sci 106:497–504. doi:10.1111/cas.12647 CrossRefPubMedPubMedCentral

27.

Goh BC, Lee SC, Wang LZ et al (2002) Explaining inter individual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol 20:3683–3890. doi:10.1200/JCO.2002.01.025 CrossRefPubMed

28.

Tobinai K, Kohno A, Shimada Y et al (1993) Toxicity grading criteria of the Japan Clinical Oncology Group. Jpn J Clin Oncol 23:250–257PubMed

29.

Noda K, Nishiwaki Y, Kawahara M et al (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85–91. doi:10.1056/NEJMoa003034 CrossRefPubMed

30.

Pettengell R, Bosly A, Szucs TD et al (2009) Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU Prospective Observational European Neutropenia Study. Br J Haematol 144:677–685. doi:10.1111/j.1365-2141.2008.07514.x CrossRefPubMed

31.

Park K, Kim JH, Cho EK et al (2016) East Asian subgroup analysis of a randomized, double-blind, phase 3 study of docetaxel and ramucirumab versus docetaxel and placebo in the treatment of stage IV non-small cell lung cancer following disease progression after one prior platinum-based therapy (REVEL). Cancer Res Treat 48:1177–1186. doi:10.4143/crt.2015.401 CrossRefPubMedPubMedCentral

32.

Ma Q, Lu AY (2011) Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 63:437–459. doi:10.1124/pr.110.003533 CrossRefPubMed

33.

Teh KL, Bertilsson L (2012) Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance. Drug Metab Pharmacokinet 27:55–67CrossRefPubMed

34.

Kadakol A, Ghosh SS, Sappal BS et al (2000) Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 16:297–306. doi:10.1002/1098-1004(200010)16:4<297:AID-HUMU2>3.0.CO;2-Z CrossRefPubMed

35.

Aapro MS, Bohlius J, Cameron DA et al (2011) 2010 Update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47:8–32. doi:10.1016/j.ejca.2010.10.013 CrossRefPubMed

36.

Crawford J, Dale DC, Kuderer NM et al (2008) Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J Natl Compr Cancer Netw 6:109–118CrossRef

Title: The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum
Authors: Takumi Fujiwara
Hirotsugu Kenmotsu
Tateaki Naito
Takahisa Kawamura
Nobuaki Mamesaya
Mie Kotake
Haruki Kobayashi
Shota Omori
Kazuhisa Nakashima
Kazushige Wakuda
Akira Ono
Tetsuhiko Taira
Haruyasu Murakami
Katsuhiro Omae
Keita Mori
Masahiro Endo
Toshiaki Takahashi
Publication date: 01-06-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-017-3324-7

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2017

Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer

Induction chemotherapy followed by concurrent chemoradiotherapy vs. concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective cohort study

Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study

A phase I study of cilengitide and paclitaxel in patients with advanced solid tumors

Enhancing the therapeutic range of a targeted small-molecule tubulysin conjugate for folate receptor-based cancer therapy

Pharmacodynamic effects in the cerebrospinal fluid of rats after intravenous administration of different asparaginase formulations

Keynote webinar | Spotlight on antibody–drug conjugates in cancer