Association between high antitumor activity of oxaliplatin and cyclophosphamide and constitutional GSTM1 homozygous deletion in an advanced ovarian cancer patient.

ABSTRACT

BACKGROUND: Although the efficiency of oxaliplatin in patients with advanced ovarian cancer has been demonstrated, it is not commonly used. In cells, oxaliplatin is metabolized by the enzymes belonging to the glutathione-S-transferase (GST) family. CASE A 55-year-old woman with advanced ovarian cancer received 6 cycles of paclitaxel and carboplatin after debulking surgery. Six months later, she experienced a clinical recurrence. A second-line chemotherapy combining 500 mg/m² cyclophosphamide with 100 mg/m² oxaliplatin was initiated and maintained for 10 cycles. The patient thus experienced a second complete remission that lasted for 6 years. We found that she had deficient GSTM1 enzyme activity with homozygous deletion and normal GSTP1 and GSTT1 activities. CONCLUSION: The association of a homozygous deletion of GSTM1 with hypersensitivity to oxaliplatin and cyclophosphamide combination chemotherapy has not been described to date in ovarian cancer. Further study of its potential interest to personalized second-line therapy in these patients is called for.