Evaluation of UGT1A1 genotyping for predicting individual toxicity of irinotecan plus platinum analog regimens: Interim safety analysis of a prospective observational study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11049-11049
Author(s):  
Masashi Takano ◽  
Kaichiro Yamamoto ◽  
Tsutomu Tabata ◽  
Yuji Minegishi ◽  
Takuma Yokoyama ◽  
...  
Keyword(s):  
Risk Factors ◽  
Observational Study ◽  
Prospective Observational Study ◽  
Daily Practice ◽  
Hematological Toxicity ◽  
Logistic Regression Models ◽  
Potential Biomarker ◽  
Independent Risk Factors ◽  
Grade 3 ◽  
Clinical Trial Information

11049 Background: Irinotecan (IRI)+platinum (Pt) therapy works synergistically and is widely used for solid carcinomas. Although UGT1A1 genotyping has been implemented in daily practice since long, recommended doses of IRI+Pt therapy according to UGT1A1 genotyping remain undetermined. Risk factors for severe toxicities of IRI+Pt regimens remain uncertain. We conducted a prospective observational study to examine the correlation between UGT1A1 genotyping and toxicity/efficacy in IRI+Pt regimens (NCT 01040312). Methods: During October 2009 and March 2012, 321 patients were enrolled. Eligible patients had histologically confirmed SCLC, non-SCLC, cervical, ovarian, or gastric cancer; had PS 0-2; and were receiving IRI+Pt (cisplatin, carboplatin, and nedaplatin) regimen, following UGT1A1 genotyping: hetero (*1/*6, *1/*28) and homo (*6/*6, *6/*28, *28/*28). Primary endpoint was to evaluate overall toxicity profile during first 3 cycles of treatment. In this interim analysis, incidences of grade 3/4 toxicities were compared among UGT1A1 phenotypes, and logistic regression models were used to identify independent risk factors for these toxicities. Results: At the time of abstract writing, toxicity data from 137 patients were available. There were 110 (80%) hetero and 27 (20%) homo genotypes. Combination therapy of IRI (57.2 ± 12.2 mg/m2 for average initial dose) and Pt analogs (cisplatin, 63%; carboplatin, 20%; nedaplatin, 17%) was administered. Incidences of grade 3/4 toxicities during first 3 cycles of treatment in hetero and homo were as follows: leukocytopenia, 38% and 59%; neutropenia, 55% and 67%; thrombocytopenia, 7% and 22%; and diarrhea, 9% and 7%. Overall grade 3/4 hematological toxicity was 50% (55/110) in hetero and 78% (21/27) in homo; the adjusted odds ratio was 3.379 (p = 0.0185) in homo compared with hetero. Conclusions: A higher rate of grade 3/4 hematological toxicity in homo than in hetero was confirmed with IRI+Pt therapy. Thus, UGT1A1 genotyping could be a potential biomarker of toxicity with individualized chemotherapy using low-dose IRI regimens. At the presentation, analysis of >250 patients’ data will be shown. Clinical trial information: NCT01040312.

scholarly journals Patterns of Anthracycline-Based Chemotherapy-Induced Adverse Drug Reactions and Their Impact on Relative Dose Intensity among Women with Breast Cancer in Ethiopia: A Prospective Observational Study

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Diriba Alemayehu Gadisa ◽  
Mathewos Assefa ◽  
Gosaye Mekonen Tefera ◽  
Getnet Yimer
Keyword(s):  
Breast Cancer ◽  
Observational Study ◽  
Adverse Drug Reactions ◽  
Prospective Observational Study ◽  
Addis Ababa ◽  
Dose Intensity ◽  
Relative Dose Intensity ◽  
Hematological Toxicity ◽  
Drug Reactions ◽  
Grade 3

Background. The breast cancer chemotherapy leads to diverse aspects of noxious or unintended adverse drug reactions (ADRs) that cause the relative dose intensity (RDI) reduced to below optimal (i.e., if the percentage of actual dose received per unit time divided by planned dose per unit time is less than 85%). Hence, this prospective observational study was conducted to evaluate chemotherapy-induced ADRs and their impact on relative dose intensity among women with breast cancer in Ethiopia. Methods. The study was conducted with a cohort of 146 patients from January 1 to September 30, 2017, Gregorian Calendar (GC) at the only nationwide oncology center, Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. The ADRs of the chemotherapy were collected using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03). The patients were personally interviewed for subjective toxicities, and laboratory results and supportive measures were recorded at each cycle. SPSS version 22 was used for analysis. Results. Grade 3 neutropenia (23 (15.8%)) was the most frequently reported ADR among grade 3 hematological toxicity on cycle 4. However, overall grade fatigue (136 (93.2%)) and grade 3 nausea (31 (21.2%)) were the most frequently reported nonhematological toxicities on cycle 1. The majority of ADRs were reported during the first four cycles except for peripheral neuropathy. Oral antibiotics and G-CSF use (17 (11.6%)) and treatment delay (31 (21.2%)) were frequently reported on cycle 3. Overall, 61 (41.8%) and 42 (28.8%) of study participants experienced dose delay and used G-CSF, respectively, at least once during their enrollment. Of the 933 interventions observed, 95 (10%) cycles were delayed due to toxicities in which neutropenia attributed to the delay of 89 cycles. Forty-four (30.1%) of the patients received overall RDI < 85%. Pretreatment hematological counts were significant predictors (P<0.05) for the incidence of first cycle hematological toxicities such as neutropenia, anemia, and leukopenia and nonhematological toxicities like vomiting. Conclusion. Ethiopian women with breast cancer on anthracycline-based AC and AC-T chemotherapy predominantly experienced grade 1 to 3 hematological and nonhematological ADRs, particularly during the first four cycles. Neutropenia was the only toxicity that led to RDI < 85%. Thus, enhancing the utilization of G-CSF and other supportive measures will improve RDI to above 85%.

scholarly journals The Incidence and Characteristics of Venous Thromboembolism in Neurocritical Care Patients: A Prospective Observational Study

2020 ◽  
Vol 26 ◽  
pp. 107602962090795
Author(s):  
Ping Zhang ◽  
Yi Bian ◽  
Feng Xu ◽  
Lifei Lian ◽  
Suiqiang Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Observational Study ◽  
Prospective Observational Study ◽  
Pulmonary Infection ◽  
Neurocritical Care ◽  
Femoral Vein ◽  
Pulmonary Arteries ◽  
Vein Thrombosis ◽  
Independent Risk Factors

Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is presumed to be high for neurologic intensive care unit (NICU) patients. However, exact incidences of VTE have yet to be reported. In this prospective observational study, we consecutively enrolled 126 neurocritical care patients who had an NICU stay ≥1 week with paralysis and/or unconsciousness. All patients received DVT prevention strategies. Patients were screened for VTE after 1 week of hospitalization, using venous ultrasonography and computed tomography pulmonary angiography. Following 1 week of NICU hospitalization, DVT incidence was 35.7% and PE incidence was 17.5%. Of the DVTs, 75.6% were in the muscular calf vein. Of the PEs, 22.7% were in main pulmonary arteries, while 77.3% were in branches. Approximately 96% of the DVTs and 86% of the PEs were asymptomatic. Approximately 24% of patients with DVT had a concurrent PE, while 50% of PE patients had a DVT. Paralysis, raised d-dimer on admission, and pulmonary infection were found to be independent risk factors for DVT. Paraplegia, femoral vein thrombosis, and pulmonary infection were found to be independent risk factors for PE. Despite active preventive measures, incidences of VTE in NICU patients were high. Most VTEs were asymptomatic, meaning they could have led to a missed diagnosis. Attention should be paid to the VTE events of critically ill neurological patients.

scholarly journals Wound infection in colorectal cancer resections through a laparoscopic approach: a single-center prospective observational study of over 3000 cases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Atsushi Ikeda ◽  
Yosuke Fukunaga ◽  
Takashi Akiyoshi ◽  
Satoshi Nagayama ◽  
Toshiya Nagasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Laparoscopic Surgery ◽  
Observational Study ◽  
Wound Infection ◽  
Prospective Observational Study ◽  
Rectal Surgery ◽  
Colonic Surgery ◽  
Laparoscopic Rectal Surgery ◽  
Independent Risk Factors

Abstract Objectives This prospective observational study aimed to clarify the incidence and independent risk factors of wound infection after laparoscopic surgery for primary colonic and rectal cancer. Methods A prospective surveillance of surgical site infection (SSI) was conducted in consecutive patients with primary colorectal cancer, who underwent elective laparoscopic surgery in a single comprehensive cancer center between 2005 and 2014. The outcomes of interest were the incidence and risk factors of wound infection. Results In total, 3170 patients were enrolled in the study. The overall incidence of wound infection was 3.0%. The incidence of wound infection was significantly higher in rectal surgery than in colonic surgery (4.7 vs. 2.1%, p < 0.001). In rectal surgery, independent risk factors for developing wound infection included abdominoperineal resection (p < 0.001, odds ratio [OR] = 11.4, 95% confidence interval [CI]: 5.04–24.8), body mass index (BMI) ≥ 25 kg/m2 (p = 0.041, OR = 1.97, 95% CI, 1.03–3.76), and chemoradiotherapy (p = 0.032, OR = 2.18, 95% CI, 1.07–4.45). In laparoscopic colonic surgery, no significant risk factors were identified. Conclusions Laparoscopic rectal surgery has a higher risk of wound infection than colonic surgery. Laparoscopic rectal surgery involving abdominoperineal resection, patients with higher BMI, and chemoradiotherapy requires careful observation in wound care and countermeasures against wound infection.

scholarly journals 5-Hydroxytryptamine-3 Receptor Antagonist and Dexamethasone as Prophylaxis for Chemotherapy Induced Nausea and Vomiting during Moderately Emetic Chemotherapy for Solid Tumors: A Multicenter, Prospective, Observational Study

2020 ◽  
Author(s):  
Reiko Matsui ◽  
Kenichi Suzuki ◽  
Tomomi Takiguchi ◽  
Makoto Nishio ◽  
Takeshi Koike ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Observational Study ◽  
Receptor Antagonist ◽  
Motion Sickness ◽  
Prospective Observational Study ◽  
Nausea And Vomiting ◽  
History Of ◽  
Independent Risk Factors ◽  
Multicenter Prospective Observational Study

Abstract Background: Of patients receiving moderate emetic risk chemotherapy (MEC), 30%–90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial. Methods: In this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Results: Of the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26–84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51% and 61% of patients, respectively. Logistic regression analysis revealed that no history of motion sickness, no history of pregnancy-associated vomiting, and non-CBDCA-based chemotherapy are independent risk factors for CR, whereas no history of motion sickness and no history of pregnancy-associated vomiting are independent risk factors for TC. Conclusion: Our data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5)+ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.

scholarly journals POS0441 DEVELOPMENT OF RHEUMATOID ARTHRITIS AMONG ANTI-CITRULLINATED PROTEIN ANTIBODIES POSITIVE ASYMPTOMATIC INDIVIDUALS: A PROSPECTIVE OBSERVATIONAL STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 449.1-449
Author(s):  
S. Mizuki ◽  
K. Horie ◽  
K. Imabayashi ◽  
K. Mishima ◽  
K. Oryoji
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Observational Study ◽  
Rheumatoid Factor ◽  
Prospective Observational Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
P Value ◽  
Healthy Population ◽  
Asymptomatic Individuals ◽  
Citrullinated Protein

Background:In the idividuals with genetic and enviromental risk factors, immune events at mucosal surfaces occur and may precede systemic autoimmunity. Anti-citrullinated protein antibodies (ACPA) are present in the serum for an average of 3-5 years prior to the onset of rheumatoid arthritis (RA) during an asymptomatic period. In ACPA-positivite individuals, the additional presence of RA-related risk factors appears to add significant power for the development of RA. To date, there have been few reports in which clinical courses of ACPA-positive asymptomatic individuals were investigated prospectively.Objectives:To observe the clinical time course of ACPA-positive healthy population for the development of RA.Methods:Healthy volunteers without joint pain or stiffness, who attended the comprehensive health screening of our hospital, were enrolled in this prospective observational study. The serum ACPA levels were quantified by Ig-G anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay with levels > 4.4 U/mL considered positive. ACPA-positive subjects were followed by rheumatologists of our department clinically or a questionnaire sent by mail for screening to detect arthritis.Results:5,971 healthy individuals without joint symptons were included. Ninty-two (1.5%) were positive for ACPA. Of these, 19 (20.7%) developed RA and two were suspected as RA by mail questionnaire. Their average age were 58-years, and women were 68%. The average duration between the date of serum sampling and diagnosis was 10.7 months. ACPA-positive individuals who developed to RA had higher serum ACPA and Ig-M rheumatoid factor levels than ACPA-positive individuals who did not (P value by Mann-Whitney U test: 0.002, 0.005, respectively).Conclusion:Among ACPA-positive asymptomatic individuals, 20% developed RA. The higher titer of ACPA and Ig-M rheumatoid factor levels are risk factors for devoloping RA.Disclosure of Interests:None declared

scholarly journals Risk factors for mortality, ICU admission and bacteremia in patients suspected of sepsis at the Emergency department. A prospective cohort study

2020 ◽  
Author(s):  
Valentino D’Onofrio ◽  
Agnes Meersman ◽  
Sara Vijgen ◽  
Reinoud Cartuyvels ◽  
Peter Messiaen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Regression Models ◽  
Serum Lactate ◽  
Suspected Sepsis ◽  
Logistic Regression Models ◽  
Icu Admission ◽  
Observational Cohort ◽  
Independent Risk Factors ◽  
Prediction Of Prognosis

Abstract Background There is a clear need for a better assessment of independent risk factors for in-hospital mortality, ICU admission, and bacteremia in patients presenting with suspected sepsis at the ED. Methods A prospective observational cohort study including 1690 patients was performed. Two multivariable logistic regression models were used to identify independent risk factors. Results SOFA score of ≥2 and serum lactate of ≥2mmol/L were associated with all outcomes. Other independent risk factors were individual SOFA variables and SIRS variables but varied per outcome. MAP&lt;70 mmHg negatively impacted all outcomes. Conclusion These readily available measurements can help with early risk stratification and prediction of prognosis.

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