Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)

Exclusion Criteria

• •1. Subject planned for intraoperative radiotherapy
• •2. Subject planned for immediate reconstruction
• •3. Neoadjuvant BC therapy
• •4. Allergy to any NSAID or gabapentinoïd
• •5. Known hypersensitivity reactions to the investigational treatments, or any excipients or auxiliary medicinal products or concomitant medications. Hypersensitive to peanut or soya (related to propofol contraindications)
• •6. Current use of the antidiabetic agent thiazolidinedione (related to interaction with pregabalin), lithium salts, probenecid, pentoxifylline or intensive diuretic therapy.
• •7. Current NSAID (\> twice a week the year prior to diagnosis) or pregabalin use
• •8. Previous malignant pathology within 5 years prior to inclusion or currently undergoing maintenance therapy. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that have undergone potentially curative therapy or in situ cervical cancer.
• •9. Active or history of peptic ulcer disease or gastro-intestinal bleeding or perforation
• •10. Pregnancy or lactating women
• •11. Chronic inflammatory disease as rheumatoid arthritis, uncontrolled asthma, chronic heart failure, chronic obstructive pulmonary disease, cystic fibrosis, inflammatory myopathies (e.g., idiopathic polymyositis, dermatomyositis, inclusion body myositis), inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), McArdle's disease, multiple sclerosis, lupus, chronic inflammatory demyelinating polyneuropathy, psoriasis, autoimmune thyroiditis as Graves' disease or Hashimoto's thyroiditis (unless previous surgical ablation), myasthenia gravis, vasculitis.
• •12. Complete or partial nasal polyposis syndrome, Quincke's oedema, bronchospasm, asthma
• •13. Known chronic infectious disease as active hepatitis B (defined as positive serology for Ac anti-HBc and IgM anti HBc OR Ac anti HBc and Ag HBs), active hepatitis C (defined as positive serology for anti-VHC and positive PCR-VHC) or active tuberculosis (included under treatment)
• •14. Uncontrolled HIV infection (defined as detectable viral loads by standard clinical assays) or controlled HIV infection (defined undetectable HIV viral loads by standard clinical assays) treated by one of following drugs: Nelfinavir, Atazanavir or Saquinavir (related to interaction with omeprazole).
• •15. Infection currently treated with one of the following drugs: posaconazole, voriconazole, ketoconazole and rifampicin, unless discontinuation of treatment is planned at least 10 days prior to the start of study treatment AND with complete resolution according to expert opinion (related to interaction with omeprazole)
• •16. Inadequate liver function (defined as total serum bilirubin ≥ 2 x upper limit of normal (ULN\<1.2 mg/dl) - unless documented Gilbert syndrome- AND Alanine Aminotransferase (ALT) ≥ 2 x ULN (ULN \<32 UI/l and ULN \<33 UI/l, respectively) AND Alkaline phosphatase (ALP) ≥ 2.5 x ULN (ULN=104 UI/l))
• •17. Cirrhosis or severe hepatitis.
• •18. Renal impairment (defined as GFR\<90ml/min/1.73m² or serum creatinine \> 442 μmol/l or \> 5 mg/dL) or single kidney or previous renal surgery
• •19. Subject with history of (severe) renal toxicity with an NSAID
• •20. Subject with a recent history of operations associated with a high risk of bleeding
• •21. Previous, ongoing or suspected cardiovascular disease defined as history of ischemic heart disease or heart failure or uncontrolled high blood pressure (Systolic ≥160mmHg and/or diastolic ≥100mmHg) or peripheral arterial disease or cerebrovascular disease
• •22. Subject with a recent history of surgery associated with a high risk of bleeding
• •23. Hemostasis disorder as haemophilia, Von Willebrand disease, constitutional thrombopathies or thrombocytopenia (defined as platelet count \< 100 000/mm³), current /planned anticoagulant or anti-platelet therapy.
• •24. Inadequate bone marrow function (defined as absolute neutrophil count \<1000/μL and platelet count \<100'000/μL)
• •25. Systemic immunosuppressive treatment (defined as systemic corticotherapy or anti-rejection treatment or interferon therapy) within the 2-years prior diagnosis
• •26. Psychiatric disease or antipsychotic/ antidepressant use
• •27. Epilepsy or any current anti-epileptic drug use
• •28. Obstructive sleep apnea
• •29. ASA≥3