1. cancer
Conditions
Interventions
Patients who will be treated with lapatinib as indicated will be asked to participate. Those patients who consent will undergo three midazolam hydroxylation tests: 1–2 days prior to their first admini
Sponsors
Erasmus MC-Daniel den Hoed
Department of Medical Oncology
Groene Hilledijk 301
3075 EA Rotterdam
the Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. Any patient who is going to be treated with lapatinib (1,250–1,500 mg once daily); 2. Age >= 18 years; 3. WHO performance status < 2.4; 4. Adequate renal and hepatic functions, as determined within two weeks before planned start of lapatinib treatment (bilirubin < 1.25xULN; aspartate and alanine transferases (ASAT and ALAT) < 2.5xUNL; alkaline phosphatase (Alk Phos) < 5xULN; serum creatinine £ 1.5xULN); 5.Written informed consent; 6. Complete initial work-up prior to the first midazolam hydroxylation test.
Exclusion criteria
Exclusion criteria: 1. Symptomatic CNS-metastases or a history of a psychiatric disorder that would prohibit the understanding and giving of informed consent; 2. Use of and/or unwillingness to abstain from grapefruit, grapefruit juice, star fruit, dietary supplements, herbal tea, herbals, and over-the-counter medication (except for acetaminophen (paracetamol) and ibuprofen) during the study period, starting 3 weeks before the first midazolam hydroxylation test and ending after the third test; 3. Use of and/or unwillingness to abstain from/absence of adequate alternatives of CYP3A, CYP2C8, CYP2C19, BCRP (ABCG2), and P-glycoprotein (ABCB1) modulating (inducing or inhibiting; see also: http://medicine.iupui.edu/flockhart/table.htm)45 co-medication during the study period, starting 3 weeks before the first midazolam hydroxylation test and ending after the third test; 4. Use of and/or unwillingness to abstain from hypnotics and anxiolytics during the study period, starting 2 weeks before the first midazolam hydroxylation test and ending after the third test; 5. Current and/or recent alcohol- and/or drug (both psycholeptics and psychodysleptics)-abuse; 6. Use of and/or unwillingness to abstain from/absence of adequate alternatives of oxazepam, temazepam and midazolam during the study period, starting 3 weeks before the first midazolam hydroxylation test and ending after the third test.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CYP3A-activity, as determined by midazolam clearance tests. | — |
Secondary
| Measure | Time frame |
|---|---|
| Auto-inhibition of lapatinib, as determined by lapatinib-levels. | — |
Contacts
Public ContactF.A. Jong, de
Erasmus Medical Center, Daniel den Hoed Kliniek Groene Hilledijk 301
Outcome results
None listed