ABSTRACT
BACKGROUND: Corrected QT (QTc) interval prolongation can induce fatal arrhythmias such as torsade de pointes. PATIENTS AND METHODS: To assess the characteristics of QTc intervals and arrhythmias in women with early breast cancer who received FEC100 adjuvant chemotherapy, electrocardiograms (ECGs) were recorded before and after each chemotherapy. Associations between QTc interval prolongation and single nucleotide polymorphisms (SNPs) of potassium channel genes were also investigated. RESULTS: A total of 131 ECG records were obtained in 34 patients who received 153 cycles of FEC100. QTc intervals could be measured in 127 records. There was a significant trend toward QTc interval prolongation after each treatment, persisting through four cycles of chemotherapy (P < 0.001). Median QTc interval prolongations were 13, 11, 18, and 14 ms in the first through fourth cycles of chemotherapy, respectively. QTc intervals differed significantly between cycles 1 and 4 before treatment as well as after treatment (P < 0.05). A single supraventricular premature contraction was noted in 3 (2.3%) of the 131 cycles in 2 (5.9%) of the 34 patients. There was no significant association between QTc interval prolongation and SNPs of potassium channel genes. CONCLUSION: This prospective study confirmed that FEC100 is associated with significant QTc interval prolongation in women with early breast cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arrhythmias, Cardiac/chemically induced , Breast Neoplasms/drug therapy , Heart/drug effects , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Arrhythmias, Cardiac/epidemiology , Chemotherapy, Adjuvant/adverse effects , Electrocardiography , Female , Genotype , Humans , Middle Aged , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Potassium Channels/genetics , Prospective Studies , Young AdultABSTRACT
OBJECTIVE: Oxaliplatin-induced chronic neuropathy is cumulative and dose-limiting; reliable predictors and determination of the mechanism of this toxic effect are needed. METHODS: We retrospectively studied 51 Japanese adults with colorectal cancer who had received oxaliplatin-based chemotherapy to explore the pharmacogenetic association between oxaliplatin-induced neuropathy and polymorphisms of the excision repair cross-complementation Group 1 (ERCC1) and glutathione-S-transferases pi 1 (GSTP1) genes. RESULTS: For the ERCC1 C118T polymorphism, Grade 1 chronic neuropathy developed earlier in patients with C/T and T/T genotypes (median number of treatment cycles at onset = 6) than in those with the reference C/C genotype (7 cycles; p = 0.0162 by the generalized Wilcoxon test). For the GSTP1 Ile105Val polymorphism, chronic neuropathy developed earlier in patients with the reference Ile/Ile genotype (6 cycles) than in those with Ile/Val and Val/Val genotypes (9 cycles; p = 0.0321). ERCC1 C118T and GSTP1 Ile105Val polymorphisms were not significantly associated with an increased risk of developing Grade 2 or more severe chronic neuropathy. CONCLUSIONS: Our results suggest that ERCC1, C118T and GSTP1 Ile105Val polymorphisms are more strongly related to the time until onset of neuropathy than to the grade of neuropathy. Most likely these polymorphisms influence patients' sensitivity to neuropathy.
Subject(s)
DNA-Binding Proteins/genetics , Endonucleases/genetics , Glutathione S-Transferase pi/genetics , Organoplatinum Compounds/adverse effects , Peripheral Nervous System Diseases/chemically induced , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asian People/genetics , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Japan , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Peripheral Nervous System Diseases/genetics , Pharmacogenetics , Polymorphism, Genetic , Retrospective Studies , Time FactorsABSTRACT
Fifty patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) underwent allogeneic bone marrow transplantation between October 1988 and January 1997. Patients received 8 mg/kg of busulfan (BU) with 120 mg/kg of cyclophosphamide (CY) followed by 10 Gy of total body irradiation (TBI). Twenty consecutive patients with AML in first remission (n = 9) or CML, in chronic phase (n = 11) entered the study (group I). Thirty consecutive patients with advanced myeloid malignancies including AML (n = 19) and CML (n = 11) also entered the study (group II). The probability of leukemia-free survival at 5 years was 85% for group I patients and 50% for group II patients. Severe regimen-related toxicities occurred in 16% of patients (two in group I, six in group II). The most common sites affected by severe toxicities were lung (n = 6), liver (n = 2) and heart (n = 2). The relapse rate was higher for patients allografted in advanced stages of disease (O% at 5 years for group I and 28% for group II). These results suggest that BU + CY + TBI is a very effective conditioning regimen in patients with myeloid malignancies.
