UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis

Abstract

Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. However, some researchers reported that UGT1A1*6 could predict IRI-induced toxicities in Asian populations, controversial conclusions still remained. Thus, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in cancer patients is still needed to be explored. Therefore, this study aims to investigate the association between UGT1A1*6 polymorphisms and IRI-related severe neutropenia in cancer patients on a large scale. A total of 12 studies that included 746 wild genotype (G/G) cases and 394 variant genotype (G/A and A/A) cases were included on the basis of inclusion criteria. Then we assessed the methodologies quality; odds ratio (OR), risk difference (RD) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, an increased risk of severe neutropenia in cancer patients with UGT1A1*6 polymorphisms was found. Patients with recessive models (GA + AA vs. GG) of UGT1A1*6 showed an increased risk (OR 2.03, 95% CI 1.54–2.68; RD = 0.11, P < 0.001). Specifically, the heterozygous variant of UGT1A1*6 showed an increased risk (OR 1.83, 95% CI 1.36–2.46; RD = 0.09, P < 0.001), and homozygous mutation showed also high risk (OR 2.95, 95% CI 1.83–4.75; RD = 0.18, P < 0.001) for severe neutropenia. Subgroup meta-analysis revealed that for patients harboring both heterozygous and homozygous variants, cancer types, low dose of IRI and the duration of treatment also presented comparably increased risk in suffering severe neutropenia. As for country, in China and Japan, there was a statistically increased severe neutropenia with variant genotype of UGT1A1*6 (China: GA + AA vs. GG, OR 1.83, 95% CI 1.28–2.59; RD = 0.08, P = 0.001; Japan: GA + AA vs. GG, OR 2.39, 95% CI 1.45–3.92; RD = 0.15, P = 0.001). In conclusion, in this meta-analysis, the UGT1A1*6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients, and increased incidences of severe neutropenia could be correlated with diverse regions, cancer type, low dose of IRI and the duration of treatment.

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UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis

Abstract

Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. However, some researchers reported that UGT1A1*6 could predict IRI-induced toxicities in Asian populations, controversial conclusions still remained. Thus, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in cancer patients is still needed to be explored. Therefore, this study aims to investigate the association between UGT1A1*6 polymorphisms and IRI-related severe neutropenia in cancer patients on a large scale. A total of 12 studies that included 746 wild genotype (G/G) cases and 394 variant genotype (G/A and A/A) cases were included on the basis of inclusion criteria. Then we assessed the methodologies quality; odds ratio (OR), risk difference (RD) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, an increased risk of severe neutropenia in cancer patients with UGT1A1*6 polymorphisms was found. Patients with recessive models (GA + AA vs. GG) of UGT1A1*6 showed an increased risk (OR 2.03, 95% CI 1.54–2.68; RD = 0.11, P < 0.001). Specifically, the heterozygous variant of UGT1A1*6 showed an increased risk (OR 1.83, 95% CI 1.36–2.46; RD = 0.09, P < 0.001), and homozygous mutation showed also high risk (OR 2.95, 95% CI 1.83–4.75; RD = 0.18, P < 0.001) for severe neutropenia. Subgroup meta-analysis revealed that for patients harboring both heterozygous and homozygous variants, cancer types, low dose of IRI and the duration of treatment also presented comparably increased risk in suffering severe neutropenia. As for country, in China and Japan, there was a statistically increased severe neutropenia with variant genotype of UGT1A1*6 (China: GA + AA vs. GG, OR 1.83, 95% CI 1.28–2.59; RD = 0.08, P = 0.001; Japan: GA + AA vs. GG, OR 2.39, 95% CI 1.45–3.92; RD = 0.15, P = 0.001). In conclusion, in this meta-analysis, the UGT1A1*6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients, and increased incidences of severe neutropenia could be correlated with diverse regions, cancer type, low dose of IRI and the duration of treatment.

http://ift.tt/2suBwCm

UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis

Abstract

Irinotecan (IRI) chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. Neutropenia is a life-threatening side effect of irinotecan, and UDP glucuronosyltransferases (UGTs) gene polymorphisms could predict the side effects in cancer patients and then reduce IRI-induced toxicity by preventative treatment or a decrease in dose. Both UGT1A1*6 and *28 were reliably demonstrated to be risk factors for IRI-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. However, some researchers reported that UGT1A1*6 could predict IRI-induced toxicities in Asian populations, controversial conclusions still remained. Thus, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in cancer patients is still needed to be explored. Therefore, this study aims to investigate the association between UGT1A1*6 polymorphisms and IRI-related severe neutropenia in cancer patients on a large scale. A total of 12 studies that included 746 wild genotype (G/G) cases and 394 variant genotype (G/A and A/A) cases were included on the basis of inclusion criteria. Then we assessed the methodologies quality; odds ratio (OR), risk difference (RD) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, an increased risk of severe neutropenia in cancer patients with UGT1A1*6 polymorphisms was found. Patients with recessive models (GA + AA vs. GG) of UGT1A1*6 showed an increased risk (OR 2.03, 95% CI 1.54–2.68; RD = 0.11, P < 0.001). Specifically, the heterozygous variant of UGT1A1*6 showed an increased risk (OR 1.83, 95% CI 1.36–2.46; RD = 0.09, P < 0.001), and homozygous mutation showed also high risk (OR 2.95, 95% CI 1.83–4.75; RD = 0.18, P < 0.001) for severe neutropenia. Subgroup meta-analysis revealed that for patients harboring both heterozygous and homozygous variants, cancer types, low dose of IRI and the duration of treatment also presented comparably increased risk in suffering severe neutropenia. As for country, in China and Japan, there was a statistically increased severe neutropenia with variant genotype of UGT1A1*6 (China: GA + AA vs. GG, OR 1.83, 95% CI 1.28–2.59; RD = 0.08, P = 0.001; Japan: GA + AA vs. GG, OR 2.39, 95% CI 1.45–3.92; RD = 0.15, P = 0.001). In conclusion, in this meta-analysis, the UGT1A1*6 polymorphisms were associated with an increased risk of IRI-induced neutropenia in cancer patients, and increased incidences of severe neutropenia could be correlated with diverse regions, cancer type, low dose of IRI and the duration of treatment.

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Adjuvant chemotherapy in resectable synovial sarcoma

Introduction

The role of adjuvant chemotherapy (AC) for synovial sarcoma (SS) is controversial. Using a large national dataset we evaluate the impact of AC on overall survival (OS) following curative-intent resection of SS.

Methods

Patients with stage I-III SS 2004-2012 undergoing resection were identified in the National Cancer Data Base. Clinicopathologic factors associated with OS were identified using Cox proportional-hazard modeling, adjusting for factors associated with receipt of AC.

Results

Among 544 patients, 131 received AC. Median age of the cohort was 42 years; 269 were female. AC was not associated with OS in univariate analysis in the overall cohort. After stratification by stage, AC was associated with prolonged OS in univariate analysis in stage III patients only (P = 0.028), which remained significant in multivariable analysis (P = 0.033). Other factors associated with OS in stage III patients were age >55 years, (P = 0.001), positive margins (P = 0.037), biphasic histology (P = 0.013), and adjuvant radiation (P < 0.001). The association between AC and OS remained significant after adjustment for factors predictive of receipt of AC.

Conclusions

In this national cohort, AC was associated with prolonged OS for SS for stage III patients but not in lower stages. Less restricted use of this therapy may be warranted in this population.

http://ift.tt/2suxtGt

Adjuvant chemotherapy in resectable synovial sarcoma

Introduction

The role of adjuvant chemotherapy (AC) for synovial sarcoma (SS) is controversial. Using a large national dataset we evaluate the impact of AC on overall survival (OS) following curative-intent resection of SS.

Methods

Patients with stage I-III SS 2004-2012 undergoing resection were identified in the National Cancer Data Base. Clinicopathologic factors associated with OS were identified using Cox proportional-hazard modeling, adjusting for factors associated with receipt of AC.

Results

Among 544 patients, 131 received AC. Median age of the cohort was 42 years; 269 were female. AC was not associated with OS in univariate analysis in the overall cohort. After stratification by stage, AC was associated with prolonged OS in univariate analysis in stage III patients only (P = 0.028), which remained significant in multivariable analysis (P = 0.033). Other factors associated with OS in stage III patients were age >55 years, (P = 0.001), positive margins (P = 0.037), biphasic histology (P = 0.013), and adjuvant radiation (P < 0.001). The association between AC and OS remained significant after adjustment for factors predictive of receipt of AC.

Conclusions

In this national cohort, AC was associated with prolonged OS for SS for stage III patients but not in lower stages. Less restricted use of this therapy may be warranted in this population.

http://ift.tt/2suxtGt

Adjuvant chemotherapy in resectable synovial sarcoma

Introduction

The role of adjuvant chemotherapy (AC) for synovial sarcoma (SS) is controversial. Using a large national dataset we evaluate the impact of AC on overall survival (OS) following curative-intent resection of SS.

Methods

Patients with stage I-III SS 2004-2012 undergoing resection were identified in the National Cancer Data Base. Clinicopathologic factors associated with OS were identified using Cox proportional-hazard modeling, adjusting for factors associated with receipt of AC.

Results

Among 544 patients, 131 received AC. Median age of the cohort was 42 years; 269 were female. AC was not associated with OS in univariate analysis in the overall cohort. After stratification by stage, AC was associated with prolonged OS in univariate analysis in stage III patients only (P = 0.028), which remained significant in multivariable analysis (P = 0.033). Other factors associated with OS in stage III patients were age >55 years, (P = 0.001), positive margins (P = 0.037), biphasic histology (P = 0.013), and adjuvant radiation (P < 0.001). The association between AC and OS remained significant after adjustment for factors predictive of receipt of AC.

Conclusions

In this national cohort, AC was associated with prolonged OS for SS for stage III patients but not in lower stages. Less restricted use of this therapy may be warranted in this population.

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Atypical presentation of sigmoid carcinoma

Abstract

Colorectal carcinoma is common worldwide and its metastasis represents the main cause of mortality related to the disease. Inguinal metastization of this tumor has been considered almost impossible, owing to colon anatomy and its cranial lymphatic drainage. We report the case of a 63-year-old man submitted to laparoscopical sigmoid colectomy, due a sigmoid adenocarcinoma. During follow-up, a right inguinal lymphadenopathy with 25 mm was detected. Fine needle aspiration biopsy revealed that it was a colon adenocarcinoma metastasis, and thus the patient underwent an inguinal lymphadenectomy. The histological study confirmed metastatic adenocarcinoma of the colon and the patient was submitted to 5-fluouracil and oxaliplatin chemotherapy. This case coursed with metastasis to the right inguinal region; although, the pathophysiological mechanism involved is difficult to understand. There are no solid data for the management of these patients. Inguinal lymphadenectomy and chemotherapy, proved to be effective.

http://ift.tt/2suOZKL