Masahide Onoue

UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients

BackgroundGene polymorphisms of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) contribute to individual variations in adverse events among patients administered irinotecan, and the distribution of the polymorphisms shows large interethnic differences. Variation in the solute carrier organic anion-transporter family, member 1B1 (SLCO1B1) gene also has a significant effect on the disposition of irinotecan in Asian cancer patients. In the present study, we evaluated the association of genetic polymorphisms of UGT1A1 and SLCO1B1 with irinotecanrelated neutropenia in Japanese cancer patients.MethodsOne hundred and thirty-five consecutive patients treated with irinotecan were enrolled. Genotypes of UGT1A1 (*60, *28, *6, and *27) and SLCO1B1 (*1b, *5, and haplotype *15) were determined by direct sequencing. Severe neutropenia refers to events observed during the first cycle of irinotecan treatment.ResultsSevere neutropenia was observed in 29 patients (22%). Six patients were homozygous and 48 heterozygous for UGT1A1*6. Only 1 patient was homozygous for UGT1A1*28. Homozygosity for UGT1A1*6 was associated with a high risk of severe neutropenia (odds ratio [OR], 7.78; 95% confidence interval [CI], 1.36 to 44.51). No significant association was found between severe neutropenia and other UGT1A1 polymorphisms or SLCO1B1 polymorphisms.ConclusionThese findings suggest that the UGT1A1*6 polymorphism is a potential predictor of severe neutropenia caused by irinotecan in Japanese cancer patients.

Surgical resection deteriorates gemcitabine-induced leukopenia in pancreatic cancer

BackgroundGemcitabine hydrochloride (GEM) is one of the most effective chemotherapeutic agents for pancreatic cancer; however, factors affecting GEM-induced leukopenia have not been clarified yet. In the present study, we analyzed the relationship between patients’ backgrounds and GEM-induced leukopenia.MethodsThirty-eight patients with pancreatic cancer were analyzed for correlation between the dose of GEM and the blood leukocyte number. Moreover, we compared leukopenia in resected and non-resected patients.ResultsThe incidence of grade 3 or 4 leukopenia was 25% in the non-resected patients, whereas equivalent leukopenia was observed in 57% of the resected patients (P = 0.048 by the χ2 test). The relative decrease in blood leukocytes induced by GEM administration was more severe in resected patients (41.3 ± 9.9%), as compared to non-resected patients (52.6 ± 16.0%; P = 0.023 by t-test).ConclusionIn the present study, we found that the administration of GEM to patients after surgical resection caused more severe leukopenia, as compared to findings in non-resected patients. These data suggested that more frequent monitoring of the leukocyte count and prolonged intervals between GEM administrations are necessary for resected patients with pancreatic cancer.

Pharmaceutical Care on Pancreatic Cancer Chemotherapy-Appropriate Usage of G-CSF (granulocyte colony-stimulating factor) for Gemcitabine-induced Leukopenia-

Pancreatic cancer is one of the most resistant malignancies and operations, radiotherapy and chemotherapy have all been widely used for the treatment of this disease. Gemcitabine, a new drug against pancreatic cancer , has been accepted for use in a palliative setting in Japan since April 2001. It is highly important for pharmacists to check for adverse effects of new drugs, especially in the case of chemotherapeutic agents, because these agents may exhibit many serious adverse effects such as hematologic toxicity that could be fatal to patients . In this study, we investigated the adverse effects of gemcitabine to improve the pharmaceutical care of patients with pancreatic cancer. In a survey of adverse effects, severe leukopenia was observed in most patients. G-CSF (granulocyte colony-stimulating factor) has been commonly used as a therapeutic agent for leukopenia, and its major principal action is to stimulate the proliferation, differentiation, and function of the granulocyte lineage in the peripheral blood. Another action is to cause marrow stem cells to migrate into the peripheral blood. Because of this latter action, it is advised that G-CSF should not be given concurrently with chemotherapeutic agents, and should be discontinued at least 24 hours before and after the administration of chemotherapeutic agents. Since there have been some patients in whom G-CSF was administered within 24 hors of gemcitabine treatment, we provided drug information about the optimal usage of G-CSF to doctors concerned . As a result, a normal level of leukocytes could be maintained, and the usage of G-CSF was decreased. In conclusion, we confirmed that leukopenia is the major adverse effect of gemcitabine in pancreatic cancer