title: Incidence of hematologic toxicity in older adults treated with gemcitabine or a gemcitabine-containing regimen in routine clinical practice: a multicenter retrospective cohort study.
abstract: OBJECTIVE
  Older adults receiving cytotoxic agents may be more susceptible to hematologic toxicities because of progressive reduction in organ functions and multiple co-morbidities. Because older adults are under-represented in clinical trials, this retrospective study aims to evaluate hematologic toxicity of gemcitabine-based regimens in older patients compared with their younger counterparts in clinical practice.
  
  
  METHODS
  A total of 494 patients routinely treated with gemcitabine, either alone or in combination with platinum-based drugs, in the Slotervaart Hospital or The Netherlands Cancer Institute between January 2003 and January 2013 were enrolled. Patient characteristics, underlying malignancy, treatment regimen, administered doses of gemcitabine, and laboratory values were retrospectively collected from electronic patient records. The relative dose intensity achieved in older patients and their younger counterparts was evaluated using the Wilcoxon rank sum test. Incidence of hematologic toxicity in older adults (age ≥70 years) and their younger counterparts (age <70 years) was compared using the Fisher's exact test. Predictors of experiencing Grade 3 or 4 hematologic toxicity were evaluated using logistic regression.
  
  
  RESULTS
  Patient characteristics and baseline laboratory values were equally distributed among the two age groups, except for the estimated glomerular filtration rate being significantly lower in the older patients. Reduction of the first administered dose of gemcitabine was significantly more frequently applied in the older patients (p = 0.03). However, no significant difference in the gemcitabine relative dose intensity over the median number of four treatment cycles was observed (65 % in the older patients group vs. 67 % in the younger control group). Incidence of severe hematologic toxicity (Grade ≥3) was not significantly higher in the older patients. A subset analysis of nadir blood counts showed a trend towards an increased incidence of Grade ≥3 hematologic toxicity for the older patients in the gemcitabine-cisplatin treatment group. Moreover, the relative risk for developing Grade 3 or 4 leukocytopenia in the older patients was increased fivefold (p = 0.007) for combination therapy with gemcitabine and cisplatin. Blood transfusions were administered nearly twofold more frequently in the older patients, but this difference did not reach statistical significance.
  
  
  CONCLUSIONS
  Treatment with gemcitabine or a gemcitabine-containing regimen appeared to be feasible and well tolerated in the older patients who were selected to receive chemotherapy. Overall, patients ≥70 years of age did not incur a higher incidence of severe or life-threatening hematologic toxicity nor did they undergo more frequent or larger dose adjustments. These data support additional treatment-specific prospective studies and clinical trials in older cancer patients to optimize treatment benefit and risk in this heterogeneous older patient population.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1006 BK, Amsterdam, The Netherlands, Marie-Rose.Crombag@slz.nl.
authors.forename: Marie-Rose B S
authors.initials: MR
authors.lastname: Crombag
authors.forename: Aurelia H M
authors.initials: AH
authors.lastname: de Vries Schultink
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006299:Health Services for the Aged; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine