Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer.

BACKGROUND: CRC is the second and third most common cancer in women and men, respectively. The national comprehensive cancer network guidelines recommend oxaliplatin-based chemotherapy as a preferred regimen for patients with advanced or metastatic colon cancer. Oxaliplatin is also used in the off-label treatment of gastric cancer. FDA uses post-marketing study commitments to gather additional information about a product's safety, efficacy, or optimal use. It is necessary to perform safety monitoring after marketing authorization is received; such monitoring can be done by means of characterizing the safety of drugs in patients being treated in real-world clinical practice settings. OBJECTIVES: This Phase IV study aimed to evaluate the safety profile of a brand-name formulation of the generic drug oxaliplatin (AlvoxalⓇ, NanoAlvand, Tehran, Iran) in Iranian patients diagnosed with either colorectal or other, different types of cancer. METHODS: Patients with colorectal cancer, gastric cancer, or other malignancies receiving oxaliplatin as a part of their treatment were included in this open-label, multicenter, observational Phase IV study. This study aimed to assess the safety profile of oxaliplatin in patients diagnosed with different cancers. FINDINGS: A total of 483 patients from 16 cities in Iran were enrolled. The most common malignancy was colorectal cancer (55.49%), followed by gastric cancer (28.16%). Based on the results, 405 patients experienced at least 1 adverse event. Most of these adverse events were grade 1 or 2, and the most commonly reported adverse event was anemia (60.66%). During the study, 26 serious adverse events occurred in 15 (3.11%) patients, which were perhaps related to oxaliplatin. There were no remarkable differences in the incidences of adverse events in the system organ classes of blood and lymphatic system disorders, gastrointestinal disorders, or nervous system disorders among patients with different malignancies (ie, colorectal cancer, gastric cancer, and other malignancies) or between genders. The results of this open-label, multicenter, observational, postmarketing surveillance study demonstrated no unexpected safety findings from the use of this oxaliplatin product (AlvoxalⓇ) in Iranian patients diagnosed with different types of cancer. CONCLUSIONS: This Phase IV study provides data on the safety profile of a number of chemotherapy regimens containing an oxaliplatin product given to Iranian patients diagnosed with different types of cancer.

Validity and reliability of the Persian version of the oropharyngeal Mucositis quality of life scale.

BACKGROUND: Oral mucositis is one of the serious complications of chemotherapy and/or radiotherapy that significantly affects the quality of patients' life. The Oropharyngeal Mucositis-Specific Quality-of-Life questionnaire (OMQoL) is an acceptable instrument for measuring the quality of life in these patients. The aim of this study was to evaluate the validity and reliability of the Persian version of OMQoL questionnaire. METHODS: This study was a cross-sectional and multi-centric research. After translation from English to Persian, back translation, and cultural adaptation, the Persian version of the questionnaire was prepared. One hundred forty-four patients suffering from oral mucositis referred to three different university affiliated hospitals related to Zahedan, Kerman and Tehran Universities of Medical Sciences, were participated in this study. Then the questionnaire was completed by trained interviewers. The reliability was assessed by Cronbach's alpha coefficient, and validity was measured through factor analysis, and construct validity (including discriminant validity, and convergent validity) methods. RESULTS: Cronbach's alpha in all dimensions was higher than 0.9 that indicated a perfect internal consistency. The results of factor analysis indicated that the dimensions specified in the Persian version were the same as the original version (Factor loading of all items > 0.4). The correlation coefficient for all items was more than 0.75, and the convergence validity was 100% in all dimensions. CONCLUSION: The results of this study showed that the reliability, and validity of Persian version of OMQoL were acceptable, which can be used to measure the quality of life in patients with oral mucositis.

Global prevalence of depression among breast cancer patients: a systematic review and meta-analysis.

PURPOSE: Depression in patients with breast cancer imposes huge costs to patients, families, and healthcare systems. The present study aimed at evaluating the global prevalence depression among patients with breast cancer. METHODS: In this meta-analysis, three electronic databases (PubMed, Web of Science, and Scopus) were searched from 1 January, 2000 until 30 March, 2019. The Hoy tool was used to evaluate the quality of the articles included in the meta-analysis. The search, screening, quality evaluation, and data extraction were carried out by two of the researchers. RESULTS: Of 47,424 studies, 72 studies performed in 30 countries entered the final stage of analysis. The global prevalence of depression was 32.2%. Specifically, the prevalence of depression was highest in the Eastern Mediterranean region and twice as high in middle-income countries as compared to developed countries. CONCLUSIONS: Regarding the high prevalence of depression in patients with breast cancer, it is vital to carry out screening within standard time periods and offer the necessary emotional support.

Health-related quality of life of breast cancer patients in the Eastern Mediterranean region: a systematic review and meta-analysis.

PURPOSE: Breast cancer is the most common type of cancer in women around the world, and this applies to the Middle East as well. The goal of all medical care and treatment is to improve the quality of life (QoL) of patients. Accordingly, the present study aimed at evaluating the QoL of patients with breast cancer in the Middle East region. METHODS: In this meta-analysis, three electronic databases (PubMed, Web of Science, and Scopus) were searched from inception until August 2018. The hoy et tool was used to evaluate the quality of the articles included in the meta-analysis. The search, screening, quality evaluation, and data extraction were carried out by two of the researchers. RESULTS: Thirty-six studies conducted on 8347 Middle Eastern women with breast cancer entered the final stage. QoL was assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire in 20 studies, with 6034 patients. The mean of the reported QoL was between 31.1 and 75.6. Based on the results of the random effect method, the overall mean of the QoL was 60.5 (95% confidence interval 56.0, 65.0; I2 = 99.0%). In six studies performed on 1053 individuals, QoL was classified as good, moderate, or poor. Less than one-third of patients (21%) had a good QoL. CONCLUSIONS: Since less than one-third of patients had a good QoL, it seems necessary to design and implement an integrated and multidimensional educational program to improve QoL of patients with breast cancer.

Common Variations in Prothrombotic Genes and Susceptibility to Ischemic Stroke in Young Patients: A Case-Control Study in Southeast Iran.

Background and Objective: Evidence indicates that genetic factors may be involved in the risk of ischemic stroke (IS). The aim of this study was to assess the effect of genetic polymorphisms located in exons or untranslated regions of MTHFR as well as FV genes on ischemic stroke. Materials and Methods: In this case-control study, 106 patients with IS and 157 healthy volunteers (age <50 years) were genotyped for MTHFR C677T, A1298C, C2572A and C4869G, FVL, and prothrombin G20210A polymorphisms. Results: The MTHFR 677CT genotype was more frequent in patients and increased risk of IS with Odds Ratio = 1.9. The MTHFR A1298C and C2572A polymorphisms were not associated with IS in dominant and recessive models. Our findings showed a significant decrease in the MTHFR 4869CG genotype in IS patients, and this variant was associated with a decreased risk of IS in the dominant model. The CAAT haplotype was associated with increased risk, and the GAAC haplotype was associated with decreased risk of IS compared to other haplotypes. There was no relation between FVL G1691A polymorphism and IS risk. Conclusions: The present study showed that the MTHFR 677CT genotype was more frequent and the MTHFR 4869CG genotype was less frequent in young IS patients.

Genetic polymorphisms of HOTAIR gene are associated with the risk of breast cancer in a sample of southeast Iranian population.

There is an increasing body of evidence which highlights the critical functions of long non-coding RNAs in the carcinogenicity mechanism of a variety of cancers. It has been reported that HOX transcript antisense intergenic RNA, a member of long non-coding RNA family, increases breast cancer risk. To date, no data regarding the association between HOX transcript antisense intergenic RNA polymorphisms and the risk of breast cancer development has been reported in Iran. Here, we examine the possible association between HOX transcript antisense intergenic RNA gene polymorphisms and breast cancer in a sample of southeast Iranian female population. The HOX transcript antisense intergenic RNA rs920778, rs12826786, rs4759314, and 1899663 gene polymorphisms were genotyped in 220 cases and 231 controls by polymerase chain reaction-restriction fragment length polymorphism. Our findings indicated that rs920778 polymorphism has significant positive association with breast cancer; rs12826786 and rs1899663 polymorphisms demonstrated significant negative association with breast cancer; and the rs4759314 variant was not associated with breast cancer risk. Haplotype analysis revealed that TGAC, CTAT, and TTAT haplotypes significantly decreased the risk of breast cancer compared with rs920778T/rs1899663G/rs4759314A/rs12826786T haplotype. In conclusion, we investigated only four variants of HOX transcript antisense intergenic RNA gene, and the findings suggest that HOX transcript antisense intergenic RNA rs920778, rs12826786, and rs1899663 polymorphisms may be associated with breast cancer risk in a sample of southeast Iranian population. Further replication studies with other polymorphisms of HOX transcript antisense intergenic RNA gene involving a greater sample size and different ethnicities are necessary to verify our findings.

Association of LIN28B Gene Polymorphisms (rs221634, rs221635, rs314276, rs9404590, and rs12194974) with Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND AND AIM: Lymphoma is a common hematopoietic cancer.  It has been proposed that LIN28B gene and its variations may have function in cancer progression and metastasis. Therefore, the purpose of this investigation has been to examine the correlation among LIN28B gene polymorphisms (such as rs221634 A>T, rs221635 T> C, rs314276 C>A, rs9404590 T>G, and rs12194974 G>A) as well as the risk of NHL in an Iranian sample. MATERIALS AND METHODS: In the current case-control research, 175 individuals with Non-Hodgkin Lymphoma along with 175 normal controls participated; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology has been utilized to the genotype samples. RESULTS: Our data demonstrated that rs12194974 and the rs221635 variants have been correlated with higher NHL risk, while rs221634 and rs314276 variants were correlated with lower risk of NHL (P≤0.05). In addition, we detected an association between rs221634 and treatment with R-CHOP. No substantial correlation has discovered among rs9404590 polymorphism and NHL in any inheritance models (P≥0.05). CONCLUSION: This was the first investigation evaluating the correlation among LIN28B gene polymorphisms as well as the occurrence of NLH. Further studies in different ethnic populations and large-scale sample size are needed to support results.

Association between PAX8AS1 (rs4848320 C > T, rs1110839 G > T, and rs6726151 T > G) and MEG3 (rs7158663) gene polymorphisms and non-Hodgkin lymphoma risk.

Long non-coding RNA (lncRNA) PAX8 antisense RNA 1 (PAX8AS1) and Maternal-expressed gene 3 (MEG3) contribute to the pathogenesis of various malignancies including non-Hodgkin lymphoma (NHL). In this study, we aimed to examine the possible association of polymorphisms of PAX8 and MEG3 and the risk NHL. A total of 175 patients and 175 healthy subjects were genotyped by PCR-RFLP and Tetra-Arms PCR assays. Results demonstrated rs4848320 C > T and rs6726151 T > G of PAX8AS1 and rs7158663 of MEG3 play a potential role in the susceptibility of NHL and PAX8AS1 rs1110839 T > G variant was associated with decreased risk of NHL. Haplotype analysis of rs1110839, rs4848320, and rs6726151 demonstrated GCG haplotype is associated with increased risk of lymphoma and TTG, TTT, and GTT haplotypes are related to decreased lymphoma susceptibility.

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND: Caspases (CASPs) are the main executors of the apoptotic process. Studies to date have shown the role of caspase-8 (CASP8) and caspase-9 (CASP9) in carcinogenesis. Therefore, the aim of this study was to investigate the associations between CASP9-rs4233532, CASP9-rs4646018, and CASP8- rs1045485 gene polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility in an Iranian population-based study. Moreover, it was examined whether such the genotype of these polymorphisms is related with clinicopathological characteristics of NHL. METHODS: 175 patients with NHL and 175 age- and sex-matched controls were enrolled in this study. We determined the genotypes of single nucleotide polymorphisms (SNPs) from CASP genes with Tetra ARMS-PCR (Amplification refractory mutation system) method. RESULTS: Statistically significant association were observed between CASP9-rs4646018 and increased risk of NHL under codominant CC, codominant TC, and dominant TC+CC genetic models. Our results showed that the A allele of CASP8-rs1045485 was a protective factor for NHL and GArs1045485 genotype significantly reduced risk of NHL. In contrast, CASP9- rs4233532 was not linked to NHL susceptibility. No relationship was detected between CASP8-rs1045485 and CASP9-rs4233532 and NHL clinicopathological characteristics, however genetic variation in CASP9-rs4646018 was associated with histology, treatment and radio therapy of NHL. CONCLUSIONS: Our study presented that the CASP8- rs1045485 and CASP9-rs4646018 polymorphisms could affect the risk of NHL in Iranian populations which was the first report to show the significant relationship between rs1045485, rs4646018 polymorphisms and NHL susceptibility. Replication large-scale case-control studies in different ethnicities are warranted to verify these findings.