A toxic interaction between mitomycin C and tamoxifen causing the haemolytic uraemic syndrome.
A comparison of patients receiving combination chemotherapy with mitomycin C, mitozantrone and methotrexate (3M) with and without tamoxifen for treatment of primary breast cancer indicates an increased risk of anaemia (P < 0.0001) and thrombocytopenia (P < 0.001), but not leucopenia for patients receiving tamoxifen with their chemotherapy compared to those receiving the chemotherapy alone. Furthermore, 9 out of 94 patients receiving tamoxifen with 3M developed progressive anaemia, thrombocytopenia and abnormal renal function as early features of microangiopathic haemolytic anaemia, progressing on to various degrees of the haemolytic uraemic syndrome (HUS). This is only rarely seen with patients receiving mitomycin C alone at higher doses than used in the 3M combination and in the presence of active metastatic disease. This syndrome can be fatal and 1 of our 9 patients died. These observations indicate that there may be an interaction between tamoxifen and mitomycin C, causing an increased incidence of anaemia, thrombocytopenia and an increased risk of HUS. The combination of these two drugs should be avoided or carefully monitored.
Montes
A
A
Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, U.K.
Powles
T J
TJ
O'Brien
M E
ME
Ashley
S E
SE
Luckit
J
J
Treleaven
J
J
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D004347:Drug Interactions; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects*; D008942:Mitoxantrone / Q000008:administration & dosage; D012189:Retrospective Studies; D013629:Tamoxifen / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced
D013629:Tamoxifen; D016685:Mitomycin; D008942:Mitoxantrone; D008727:Methotrexate