Phenotyping Study of Cyclophosphamide 4-Hydroxylation in Malay Cancer Patients

Abstract

Background

Cyclophosphamide (CP) is an anticancer alkylating group (nitrogen mustard) and a prodrug that will be metabolized to form its active metabolite, 4-hydroxycyclophosphamide (4-OHCP). The various enzymes involved in its bioactivation can cause a wide range of CP expression and activity among patients and ultimately affect the metabolism, efficacy and toxicity of this drug. The effectiveness of CP therapy can be determined by 4-OHCP level in dried blood spot (DBS).

Aim

The purpose of this study was to conduct the phenotyping of CP 4-hydroxylation rate in Malay cancer patients.

Methodology

Phenotyping study of CP 4-hydroxylation rate to 40 subjects of Malay cancer patients was done based on the value of its bioactivity ratio (4-OHCP to CP levels).

Results

The result shown the cyclophosphamide 4-hydroxylation rate of 80% (n=32) subjects as ultrarapid metabolizer (UM) and 20% (n=8) as poor metabolizer (PM).

Conclusion

Phenotyping study of CP 4-hydroxylation in Malay cancer patients can be conducted by quantifying CP bioactivity ratio (4-OHCP to CP level) in dried blood spot. In majority of Malay cancer patients, cyclophosphamide would be bioactivated through 4-hydroxylation in hepar rapidly as indicated by the high value of the bioactivity ratio or the increased CP clearance and 4-OHCP level.