Myelosuppression in a Metastatic Breast Cancer Patient with GSTP1 rs1695
Mutation Induced by Adriamycin and Cyclophosphamide
Abstract
Introduction: Adriamycin and cyclophosphamide (AC) combination
chemotherapy is one of the common regimens used for breast cancer and in
metastatic breast cancer with oligo-metastasis. (1) AC combination
chemotherapy regimen is associated with adverse drug reactions like
myelosuppression, gastrointestinal toxicity, cardiotoxicity, peripheral
neuropathy, and hand-foot syndrome. (2),(3),(4) It has been noticed from
previous studies that the metabolism-related gene GSTP rs 1695
homozygous mutant allele has been associated with higher incidences of
myelotoxicity and gastrointestinal toxicity post-combination
chemotherapy regimens. (5) Case report: A 55-year-old female patient
presented with the incidence of grade 3 febrile neutropenia and
myelosuppression, 8 days following AC infusion. The patient also has
symptoms of grade 2 peripheral neuropathy and diarrhea. She was treated
as an inpatient from the local hospital with pegfilgrastim, packed RBC
transfusion, and intravenous antibiotics for febrile neutropenia. She
recovered completely with this treatment and was discharged without any
sequelae or complications. She was then tested for the GSTP rs 1695 gene
which revealed the homozygous mutant variant (GG allele). When reporting
the causal association of the adverse drug reaction, it comes under the
“possible” category of WHO causality assessment. Conclusion:
Myelosuppression, Diarrhea, and other adverse events following AC
combination chemotherapy can be related to the Genetic polymorphism in
GSTP rs 1695 double mutant homozygous allele (GG ) and its altered drug
metabolism effects. The Adverse drug reaction comes under the
“Possible” Category of WHO causality assessment. Key Words:
Adriamycin, Myelosuppression, Cyclophosphamide, Hand-foot syndrome, GSTP
rs1695