title: Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study.
abstract: BACKGROUND
  Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited.
  
  
  OBJECTIVE
  The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment.
  
  
  METHODS
  For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 × 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents.
  
  
  RESULTS
  A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%).
  
  
  CONCLUSIONS
  The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose-dependent thrombocytopenia a dose reduction may be sufficient.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Ten Berg
authors.forename: Patricia M L A
authors.initials: PM
authors.lastname: van den Bemt
authors.forename: Sumitra
authors.initials: S
authors.lastname: Shantakumar
authors.forename: Dimitri
authors.initials: D
authors.lastname: Bennett
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.forename: Albert
authors.initials: A
authors.lastname: Huisman
authors.forename: Wouter W
authors.initials: WW
authors.lastname: van Solinge
authors.forename: Toine C G
authors.initials: TC
authors.lastname: Egberts
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
references.citation: Gastroenterol Clin Biol. 2006 May;30(5):797-8
references.pmid: 16801909
references.citation: Cancer Chemother Pharmacol. 2008 Oct;62(5):925-7
references.pmid: 18204841
references.citation: J Thromb Thrombolysis. 2008 Oct;26(2):125-31
references.pmid: 18034323
references.citation: Am J Hematol. 2006 Mar;81(3):193-8
references.pmid: 16493620
references.citation: J Clin Oncol. 1994 Nov;12(11):2317-20
references.pmid: 7964946
references.citation: J Natl Cancer Inst. 2006 Aug 16;98(16):1108-17
references.pmid: 16912263
references.citation: Drug Saf. 2009;32(1):69-76
references.pmid: 19132806
references.citation: Clin Colorectal Cancer. 2009 Oct;8(4):220-4
references.pmid: 19822513
references.citation: BMJ. 2004 Jul 3;329(7456):44-7
references.pmid: 15231627
references.citation: Cancer. 1984 Feb 1;53(3):557-62
references.pmid: 6692260
references.citation: J Clin Oncol. 2002 Dec 15;20(24):4636-42
references.pmid: 12488407
references.citation: Clin Ther. 2009;31 Pt 2:2416-32
references.pmid: 20110050
references.citation: Pharmacotherapy. 2000 Mar;20(3):292-307
references.pmid: 10730685
references.citation: Clin Chem Lab Med. 2007;45(1):13-9
references.pmid: 17243908
references.citation: Cancer Res. 2007 May 15;67(10):4767-73
references.pmid: 17510405
references.citation: Drug Saf. 2000 Jun;22(6):415-23
references.pmid: 10877036
references.citation: Oncologist. 1998;3(1):15-34
references.pmid: 10388081