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1.
Cancer ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682652

ABSTRACT

BACKGROUND: Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19-9 (CA 19-9) response (decrease ≥50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine-based chemotherapy. METHODS: This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin-bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19-9 response and OS. The significance level was set at 5%. RESULTS: In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19-9 response could be assessed were included in the final analysis. Patients who had a CA 19-9 response had significantly longer OS (372 vs. 241 days; p = .007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19-9 response and OS, but it was not statistically significant. COX-2 -765G>C polymorphism did not significantly correlate with CA 19-9 response but was significantly associated with OS (hazard ratio, 2.031; p = .019). CONCLUSIONS: Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX-2 polymorphisms involved in tumor cell proliferation might affect OS.

2.
Sci Rep ; 13(1): 19457, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37945672

ABSTRACT

Treatment using docetaxel (DOC) and ramucirumab (RAM) is an effective regimen in second or later line advanced non-small cell lung carcinoma (NSCLC) treatment. However, it induces severe adverse effects, resulting in treatment reduction such as dose reduction and/or discontinuation. This study aimed to reveal the factor(s) associated with treatment reduction in DOC + RAM. We retrospectively evaluated patients with advanced NSCLC (n = 155). Treatment reduction of the second course due to severe adverse effects was conducted in 25.8% of the participants, and relative dose intensity at the second course was 95.7 ± 8.4% for DOC and 91.9 ± 24.8% for RAM. Multivariate logistic regression analyses identified that baseline anemia and prophylactic granulocyte colony-stimulating factor (G-CSF) administration are preventive factors for the reduction (adjusted odds ratio, 0.29; 95% confidence interval, 0.12-0.66; P = 0.004 for baseline anemia, 0.18; 0.08-0.42; P < 0.0001 for prophylactic G-CSF administration). The primary cause of the reduction was febrile neutropenia, and the same factors were identified. Our study revealed that patients with baseline anemia and prophylactic G-CSF administration have less risk for treatment reduction in DOC + RAM for NSCLC treatment.


Subject(s)
Anemia , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel/therapeutic use , Lung Neoplasms/pathology , Retrospective Studies , Granulocyte Colony-Stimulating Factor/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Anemia/etiology , Ramucirumab
3.
Sci Rep ; 13(1): 17126, 2023 10 10.
Article in English | MEDLINE | ID: mdl-37816823

ABSTRACT

The occurrence of cisplatin (CDDP)-induced nephrotoxicity (CIN) has decreased with advancements in supportive care. In contrast, we reported that baseline diabetes mellitus (DM) complications significantly worsen CIN. This study aimed to determine further risk factors associated with CIN development in DM patients. Patients with thoracic cancer requiring DM pharmacotherapy, who received CDDP (≥ 60 mg/m2)-containing regimens using the short hydration method (n = 140), were enrolled in this retrospective multicenter observational study. The primary endpoint of the present study was the elucidation of risk factors (patient factors, DM medication influence, and treatment-related factors) associated with CIN development in patients with DM. Cisplatin-induced nephrotoxicity occurred in 22.1% of patients with DM. The median worst variation of serum creatinine levels and creatinine clearance (worst level - baseline level) was 0.16 mg/dL (range: - 0.12-1.41 mg/dL) and - 15.9 mL/min (- 85.5-24.3 mL/min), respectively. Multivariate logistic regression analyses identified female sex as the singular risk factor for CIN development in the DM population (adjusted odds ratio; 2.87, 95% confidence interval; 1.08-7.67, P = 0.04). Diabetes mellitus medication and treatment-related factors did not affect CIN development. In conclusion, our study revealed that female sex is significantly associated with CIN development in patients with DM and thoracic cancer.


Subject(s)
Diabetes Mellitus , Kidney Diseases , Neoplasms , Renal Insufficiency , Humans , Female , Cisplatin/adverse effects , Risk Factors , Renal Insufficiency/complications , Neoplasms/drug therapy , Retrospective Studies , Creatinine , Contrast Media/adverse effects , Kidney Diseases/chemically induced
4.
Eur J Clin Pharmacol ; 79(3): 407-414, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36645467

ABSTRACT

PURPOSE: Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: The medical records from 214 patients with ES-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4, and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using the COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP group and 47 patients in the EP group. RESULTS: No significant difference was found between grades 0-3 and grade 4 neutropenia and overall survival (OS) in the EP group (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grades 0-3 and 633 days for grade 4 neutropenia, which was significantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identified as a significant predictor of longer OS (hazard ratio [HR], 0.50; 95% confidence interval (CI), 0.28-0.87, P = 0.015). CONCLUSION: The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.


Subject(s)
Antineoplastic Agents , Lung Neoplasms , Neutropenia , Small Cell Lung Carcinoma , Humans , Lung Neoplasms/drug therapy , Prognosis , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neutropenia/chemically induced , Cisplatin/adverse effects , Antineoplastic Agents/therapeutic use
5.
Cancer Med ; 11(20): 3743-3750, 2022 10.
Article in English | MEDLINE | ID: mdl-35434933

ABSTRACT

BACKGROUND: First-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sometimes causes lung injury, thereby affecting survival. Although pre-existing interstitial lung abnormal shadow (pre-ILS) increases the risk of lung injury by EGFR-TKIs, its impact on osimertinib, a third-generation EGFR-TKI, remains unknown. PATIENTS AND METHODS: This retrospective cohort study consecutively enrolled patients of EGFR-mutated non-small cell lung cancer treated with osimertinib. Computed tomography images were obtained and evaluated independently by three pulmonologists in a blinded manner. Factors associated with lung injury were assessed using a logistic regression model. Survival curves were calculated by the Kaplan-Meier method and compared using a log-rank test. RESULTS: Of the 195 patients, 40 had pre-ILS, and 21 (8 with and 13 without pre-ILS) developed lung injury during the observation period. Multivariate analysis revealed that pre-ILS was independently associated with lung injury (odds ratio, 3.1; 95% confidence interval [CI], 1.1-8.2; p = 0.025). Severe (≥Grade 3) lung injury was observed in eight (4.1%) patients, of whom, two (5%) and six (3.9%) had and did not have pre-ILS (p = 0.67), respectively. Grade 5 lung injury was not observed, and survival curves were similar between the patients who developed lung injury and those who did not (median 11 vs. 12 months; hazard ratio, 1.2; 95% CI, 0.56-2.7; p = 0.60). CONCLUSIONS: Pre-ILS increased the risk of lung injury in patients of non-small cell lung cancer treated with osimertinib, while the severity of lung injury was not clearly affected by the presence of pre-ILS.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Retrospective Studies , ErbB Receptors/genetics , Mutation , Protein Kinase Inhibitors/adverse effects , Lung
6.
Biol Pharm Bull ; 44(4): 474-477, 2021.
Article in English | MEDLINE | ID: mdl-33790098

ABSTRACT

CT-P6 is a biosimilar of trastuzumab and is recommended to be administered for 30-90 min in subsequent maintenance infusions to prevent infusion-related reactions (IRRs). We administered CT-P6 for 30 min as the first injection and as an alternative to reference trastuzumab in the maintenance infusion and evaluated the safety of the administration. A total of 140 patients with breast or gastric cancer, who received a switch from tri-weekly reference trastuzumab to CT-P6 for 30 min in maintenance infusions, were retrospectively evaluated. Premedication was administered prior to an infusion of CT-P6 and a cytotoxic agent. However, premedication was not provided when CT-P6 was co-administered with pertuzumab or administered alone. The primary endpoint was the incidence of IRRs. The secondary endpoint was the incidence of diarrhea and skin toxicity. Ninety-five percent of the patients had breast cancer, and 44.3% had advance-stage cancer. The treatment included CT-P6 alone (17.9%) or with cytotoxic agents (23.6%), antihormonal drugs (25.7%), and pertuzumab (62.9%). Median administration time of trastuzumab at the switch was 13 administrations (range 2-140). Premedication was administered to 20.7% patients. One patient (0.7%) experienced grade 3 IRR. The frequency of diarrhea in the reference trastuzumab group and the CT-P6 group was 7.1 and 6.4%, respectively, and that of skin toxicity was 6.4 and 5.0%, respectively, without differences. In conclusion, we first demonstrated that an initial CT-P6 administration for 30 min during the switch from reference trastuzumab in maintenance infusion is an acceptable administration method.


Subject(s)
Antineoplastic Agents, Immunological/administration & dosage , Biosimilar Pharmaceuticals/administration & dosage , Breast Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Trastuzumab/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/adverse effects , Drug Administration Schedule , Drug Substitution , Female , Humans , Infusions, Intravenous , Maintenance Chemotherapy , Male , Middle Aged , Retrospective Studies
7.
Clin Breast Cancer ; 18(2): e157-e165, 2018 04.
Article in English | MEDLINE | ID: mdl-28735677

ABSTRACT

INTRODUCTION: Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV. PATIENTS AND METHODS: We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes. RESULTS: Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049). CONCLUSION: The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Antibiotics, Antineoplastic/adverse effects , Antiemetics/therapeutic use , Breast Neoplasms/drug therapy , Nausea/genetics , Neoplasm Proteins/genetics , Adult , Anthracyclines/adverse effects , Aprepitant/therapeutic use , Breast Neoplasms/genetics , Dexamethasone/therapeutic use , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Nausea/chemically induced , Nausea/drug therapy , Nausea/epidemiology , Odds Ratio , Palonosetron/therapeutic use , Polymorphism, Single Nucleotide , Prospective Studies , Risk Factors , Treatment Outcome , Vomiting/chemically induced , Vomiting/drug therapy , Vomiting/epidemiology , Vomiting/genetics
8.
Intern Med ; 55(22): 3295-3299, 2016.
Article in English | MEDLINE | ID: mdl-27853072

ABSTRACT

Resistance to thyroid hormone (RTH) is a genetic disorder characterized by reduced tissue responsiveness to thyroid hormone. We herein describe a 60-year old man who presented with the clinical features of cardiomyopathy, diabetes mellitus and elevated thyroid hormones with unsuppressed thyroid stimulating hormone. A genetic analysis of thyroid hormone receptor (TR) revealed a missense mutation (A268D) in the TRß gene. Clinical manifestations of RTH may be variable due to different tissue distributions of TR subtypes and different actions of mutant receptors. The current case demonstrates that patients with a TRß mutation may have impaired his glucose metabolism and a reduced cardiac function, although patients appear clinically euthyroid.


Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/complications , Heart Failure/complications , Thyroid Hormone Receptors beta/genetics , Thyroid Hormone Resistance Syndrome/complications , Thyroid Hormone Resistance Syndrome/genetics , Diabetes Mellitus, Type 2/blood , Humans , Male , Middle Aged , Mutation, Missense , Receptors, Thyroid Hormone/blood , Thyrotropin/blood
9.
Gan To Kagaku Ryoho ; 43(4): 435-8, 2016 Apr.
Article in Japanese | MEDLINE | ID: mdl-27220788

ABSTRACT

With the approval of pegfilgrastim, the use of dose-dense epirubicin and cyclophosphamide (EC) for breast cancer has become acceptable in Japan. Thus, we aimed to evaluate its safety and tolerability in Japanese patients. Nine breast cancer patients with a high risk of preoperative or postoperative recurrence received EC therapy(epirubicin 90 mg/m(2) and cyclo- phosphamide 600 mg/m(2))for 4 cycles every 2 weeks in combination with a subcutaneous injection of pegfilgrastim (3.6 mg) on day 2 of each cycle. Treatment was discontinued in 1 and extended in 1 of the 9 patients, and the mean relative dose intensity(RDI)was good at 0.93. No serious adverse events were observed, indicating good tolerability. The regimen has potential for use in cases in which the treatment dose needs to be increased. grade 4 neutropenia was observed in all the 9 patients on day 8, with 6 patients developing febrile neutropenia. In Japan, data on changes in neutrophil count associated with pegfilgrastim administration under anthracycline-based chemotherapy are currently insufficient, and further study is required.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/surgery , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Drug Tolerance , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Middle Aged , Polyethylene Glycols , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects
10.
Gan To Kagaku Ryoho ; 43(2): 219-22, 2016 Feb.
Article in Japanese | MEDLINE | ID: mdl-27067686

ABSTRACT

Although GC therapy (the traditional 4-week[4W]regimen)is administered to urothelial cancer patients, discontinuation of gemcitabine after 15 days of administration is a problem. One solution is to use a 3-week (3W) regimen. Because a Japanese study comparing the 3W to the 4W regimens reported the lower efficacy and safety of the 3W regimen, we compared these regimens in a retrospective study. Leukopenia of Grade≥occurred in 18% and 18% of cases and anemia of Grade≥3 occurred in 28% and 39% of cases treated with the 3W and 4W regimens, respectively. On the other hand, thrombocytopenia of Grade≥3 occurred in 13% and 39% of cases treated with the 3W and 4W regimens, respectively (p< 0.001). In addition, overall survival was 14.8 months and 15.0 months for the 3W and 4W regimens, respectively (p=0.97). Thus, the 3W regimen as an alternative treatment instead of the 4W regimen is considered a highly tolerated regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Urologic Neoplasms/drug therapy , Urothelium , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Gemcitabine
11.
Gan To Kagaku Ryoho ; 42(5): 591-4, 2015 May.
Article in Japanese | MEDLINE | ID: mdl-25981653

ABSTRACT

The purpose of this study was to extract the risk factors for GradeB3 leukopenia induced by docetaxel plus prednisolone (DP)therapy administered to patients with castration-resistant prostate cancer. Rates of 59% for GradeB3 leukopenia and 11% for FN were observed. On multivariate analysis, the pretreatment white blood cell count(OR=0.502, 95%CI: 0.292- 0.862, p=0.01)was significantly associated with severe leukopenia induced by DP therapy. In addition, on univariate analysis, the pretreatment platelet count, disease extent, and bilirubin level were significant factors. We consider it necessary to immediately treat patients with these risks with G-CSF.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukopenia/chemically induced , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel , Humans , Male , Middle Aged , Prednisolone/administration & dosage , Prednisolone/adverse effects , Retrospective Studies , Risk Factors , Taxoids/administration & dosage , Taxoids/adverse effects
12.
Opt Express ; 21(1): 463-8, 2013 Jan 14.
Article in English | MEDLINE | ID: mdl-23388940

ABSTRACT

This paper proposes a 40Gbit/s-class-λ-tunable WDM/TDM-PON for flexible photonic aggregation networks that achieves the aggregation of a large number of users using the DWBA algorithm without an L2-SW. It also clarifies the scalability of the proposed system in terms of the transmission distance and the number of users. A λ-switching transmission experiment was conducted using a newly developed 10Gbit/s x 4λ selectable B-Tx and 4 x 4 cyclic AWG router.

13.
Opt Express ; 20(26): B1-6, 2012 Dec 10.
Article in English | MEDLINE | ID: mdl-23262838

ABSTRACT

We propose a cyclic NxN AWG router that can multi/demultiplex upstream and downstream signals with different channel spacings in different wavelength regions. We fabricated a 4 x 4 AWG router for our novel λ-tunable WDM/TDM-PON using silica-based PLC technology and showed that it can cyclically multi/demultiplex both 20 nm-spaced and 200 GHz-spaced signals at 1.3 and 1.5 µm, respectively.

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