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


METHODS
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.


CONCLUSIONS
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.
Oncologie Médicale, Hôpital Cochin, Paris, France.
Ithar
I
Gataa
George
G
Emile
Marie-Anne
MA
Loriot
François
F
Goldwasser
Jérôme
J
Alexandre
D000483:Alleles; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000627:therapeutic use; D012008:Recurrence
D000970:Antineoplastic Agents; D016190:Carboplatin; D003520:Cyclophosphamide; D005982:Glutathione Transferase; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017239:Paclitaxel