Retrospective cohort study to assess the increased risk of myelotoxicity due to the combined use of fluoropyrimidines and thiazides

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  CAPECITABINE ACCORD
• Medicinal product name, other:
  Tegafur; 5-Fluorouracil; Hydrochlorothiazide; Bendroflumethiazide; Indapamide; Chlorthalidone
• Study drug International non-proprietary name (INN) or common name:
  CAPECITABINE

  HYDROCHLOROTHIAZIDE

  INDAPAMIDE

  OXALIPLATIN
• Anatomical Therapeutic Chemical (ATC) code:
  (A) ALIMENTARY TRACT AND METABOLISM

  ALIMENTARY TRACT AND METABOLISM

  (C03AA01) bendroflumethiazide

  bendroflumethiazide

  (C03AA03) hydrochlorothiazide

  hydrochlorothiazide

  (C03BA11) indapamide

  indapamide

  (L01BC02) fluorouracil

  fluorouracil

  (L01BC03) tegafur

  tegafur

  (L01BC06) capecitabine

  capecitabine
• Medical condition to be studied:
  Anal cancer

  Colon cancer

  Chemotherapy

Population studied

• Short description of the study population:
  Patients treated with capecitabine or capecitabine-oxaliplatin due to colorrectal/anal cancer
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  192

Study design details

• Study design:
  Retrospective cohort of patients treated with fluropyrimidines due to cancer in order to compare the incidence of mielotoxicity and other adverse events in patients thar are treated with thiazides or not.
• Main study objective:
  To compare the incidence of mielotoxicity of patients treated in combination with fluoropyrimidines and thiazides in comparision with patients not treated with thiazides.
• Setting:
  Patients treated in our hospital by the medical oncology department
• Comparators:
  Patients treated with thiazides and fluoropyrimidines versus treated only with fluoropyrimidines.
• Outcomes:
  Myelotoxicity defined as: Anemia, leukopenia, neutropenia, lymphopenia and thrombocytopenia. ; Clinical significance of those adverse events: febril neutropenia, hemorrhage, number of infections, oral mucositis and skin reactions
• Data analysis plan:
  Relative risk of mielotoxicity will be compared between both grups, those treated with thiazides and those not treated.
• Summary results:
  We included 192 patients (mean age 68.6±13 years; 61.5% male); 37 (19.3%) were on thiazides at treatment start. Baseline characteristics, including chemotherapy type, did not differ between groups. Median follow-up was 125 days (IQR 75.8). Hemoglobin declined significantly in thiazide users at 1–3 months (-0.3 vs +0.11g/dL;p=0.006) and >6 months (-2.63 vs -0.75g/dL; p=0.002). Other hematologic parameters showed no significant differences. Myelotoxicity occurred in 83.8% of thiazide users vs 75.5% in controls (RR=1.11; 95%CI: 0.94–1.31;p=0.280). ; No differences were seen in febrile neutropenia, mucositis, infections, or other AEs. Logistic regression did not identify any risk factor for myelotoxicity risk. ; Concomitant use of fluoropyrimidines and thiazides was not associated with higher myelotoxicity or adverse events. SmPC and drug-interaction warnings should be reconsidered.