A comparative study to assess the effectiveness of curcumin, mucosamin, and chlorhexidine in chemotherapy-induced oral mucositis.

BACKGROUND: Oral mucositis is one of the most frequent and challenging side effects of chemotherapy. At present, none of the guidelines recommend the use of various mouthwashes available for the treatment of oral mucositis. METHODS: This study was designed to evaluate the efficacy of curcumin, mucosamin, and chlorhexidine in the treatment of chemotherapy-induced oral mucositis. In this randomized and double-blind study, 71 patients over 18 years, who received chemotherapy and suffered from chemotherapy-induced oral mucositis, were randomized into curcumin, mucosamin, and chlorhexidine groups. The World Health Organization (WHO) Oral Toxicity Scale, the Oral Mucositis Assessment Scale (OMAS), and the Numerical Rating Scale (NRS) were used to evaluate oral mucositis. The main endpoint included the onset of complete recovery after starting the treatment. FINDINGS: Based on the WHO, OMAS for erythema, and NRS criteria, complete recovery was achieved from the third day in the curcumin group, which was significantly earlier compared to the other two groups (P < 0.05). The OMAS score for ulceration represented an improvement from day 5 in the curcumin group, which was significantly faster compared to the other two groups (P = 0.04). CONCLUSIONS: Our results indicated that all three approaches were effective in improving oral mucositis; however, curcumin could result in faster recovery in comparison with mucosamin and chlorhexidine. The use of curcumin in the treatment of oral mucositis appears to be a viable intervention for reducing potential compromise to treatment and improving the quality of life.

Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients.

BACKGROUND: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. METHODS: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. CONCLUSIONS: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.

An Open-Label, Single-Arm, Pilot Intervention Study to Assess the Efficacy and Safety of Apixaban in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction due to its related risk of life- and limb-threatening thrombosis. Apixaban is a direct factor Xa inhibitor that may be intended as an ideal alternative for the management of HIT. In this open-label, single-arm, pilot intervention study, the efficacy and safety of apixaban were evaluated in 30 patients aged >18 years with clinically suspected HIT (4Ts score ≥4 points). Patients with mechanical heart valves, chronic kidney disease, hepatic impairment, and active bleeding were excluded. In all patients with inclusion criteria, heparin or enoxaparin was discontinued and apixaban was started. The dose of apixaban for HIT suspected patients was defined on the basis of the reason for anticoagulant therapy. End points included confirmed thrombosis, mortality, and adverse treatment-related events. After apixaban therapy, platelet counts normalized in all patients; none of the 30 subjects developed new, progressive, or recurrent thrombosis; and only 1 of 30 patients developed a hemorrhagic event. Five patients (16.7%) died, but the reason for death was not linked to thrombosis, hemorrhage, or adverse effects of apixaban. Along with the available emerging data, our results propose that apixaban could be a safe and effective drug for the management of suspected HIT in clinically stable patients.

A Post-Marketing Surveillance Study to Evaluate the Safety Profile of AlvotereⓇ (Docetaxel) in Iranian Patients Diagnosed with Different Types of Cancers Receiving Chemotherapy.

BACKGROUND: Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non-small cell lung cancer, and prostate cancer. OBJECTIVE: This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel. METHODS: Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets. FINDINGS: A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants' mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher (P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens. CONCLUSIONS: The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

The effect of CHRNA3 rs1051730 C>T and ABCB1 rs3842 A>G polymorphisms on non-small cell lung cancer and nicotine dependence in Iranian population.

AIMS: Lung cancer is still the leading cause of cancer mortality in all over the world. Nicotine and its derivatives are the most well-known carcinogens that participate in both etiology and progression of lung cancer. The objective of the current study was to investigate whether single nucleotide polymorphisms (SNPs) rs1051730C > T in CHRNA3 and rs3842A > G in ABCB1, two genes contributing in the mechanism of disposition and metabolism of nicotine and its derivatives, could modify the risk of developing lung cancer, as well as nicotine dependence in Iranian. MAIN METHODS: The genotyping analysis for these two SNPs was conducted in a case-control study of 108 lung cancer cases and 120 healthy controls using ARMS-PCR and Tetra-primer ARMS-PCR techniques. The correlation between studied SNPs and lung cancer was assessed by the regression analysis. KEY FINDINGS: We observed a significant association between lung cancer and rs1051730C > T by using four genetic models: allele (OR:1.83; 95% CI:1.24-2.6; p = 0.002), dominant (OR: 2.19; 95% CI:1.27-3.78; p = 0.005), recessive (OR: 2.25; 95% CI: 1.02-4.95; p = 0.043) and additive (TT vs CC: OR:3.25; 95% CI:1.38-7.60; p = 0.007, CT vs CC: OR:1.96; 95% CI:1.10-3.48; p = 0.021). Furthermore, a significant association between this variant and nicotine dependence (OR: 2.27; 95% CI: 1.52-3.39; p = 0.00005) was reported. However, no association was found for rs3842A > G. SIGNIFICANCE: The results suggested that the CHRNA3 rs1051730C > T via a smoking-dependent manner could modify susceptibility to lung cancer among Iranian population.

Relationship between weight gain and survival rate in patients with metastatic lung cancer.

Background: Lung cancer accounts for about 13% of all cancers and about 60% of patients with lung cancer also experience weight loss during treatment. There seems to be a clear correlation between the therapeutic outcomes of patients based on their weight changes during treatment. The aim of this study was to investigate the relationship between weight changes during and after treatment and the therapeutic outcomes of a patient with metastatic lung cancer. Methods: This cohort study was performed on patients with the diagnosis of non-surgical metastatic lung cancer referred to Hematology and Oncology Clinic, Rasoul-e-Akram Hospital. Patients were divided into two groups with a weight gain of more than 5% and a weight gain of 5% and less. The information was entered into the SPSS version 21 software. In the descriptive analysis, mean and standard deviation (SD) were used. To compare quantitative variables, independent samples t-test, Mann-Whitney, chi-square or Fisher exact tests were used to compare qualitative variables and correlation test was used to determine the correlation between quantitative data. Survival curves were used to show differences in two groups of studies. A regression model was used to calculate the hazard ratio. The significance level was less than 0.05. Results: Sixty patients, including 40 males (66.7%) and 20 females (33.3%) were studied. The mean age of patients was 62.22±9.00 years (43-83 years). The mean weight changes in the patients were -1.28±6.11 kg (-16 to 16kg). Forty-seven patients (78.3%) had weight gain less than 5%. There was no significant difference in overall survival (OS) and progression-free survival (PFS) according to weight gain. Conclusion: Finally, the findings of the study showed that, despite the fact that PFS and OS in the weight gain group were greater than 5% of the original weight; the difference was not statistically significant.

The Role of Dihydropyrimidine Dehydrogenase and Thymidylate Synthase Polymorphisms in Fluoropyrimidine-Based Cancer Chemotherapy in an Iranian Population.

BACKGROUND: The fluoropyrimidine drug 5-Fluorouracil (5-FU) and the prodrug capecitabine have been extensively used for treatment of many types of cancer including colorectal, gastric, head and neck. Approximately, 10 to 25% of patients suffer from severe fluoropyrimidine-induced toxicity. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for the identification of predictive markers in chemotherapy treatment. The aim of the study was to investigate the role of five genetic polymorphisms within two genes (DPYD, TYMS) in toxicity and efficacy of fluoropyrimidine-based chemotherapy. METHODS: Total genomic DNA was extracted from 83 cancer patients treated with fluoropyrimidine-based chemotherapy. In this study, three polymorphisms were genotyped in dihydropyrimidine dehydrogenase gene c.1905+1 G>A (DPYD*2A; rs3918290), c.1679 T>G (I560S; DPYD*13; rs55886062), and c.2846A>T (D949V; rs67376798) and two polymorphisms, besides the Variable Number of Tandem Repeat (VNTR) polymorphism and 6-bp insertion/deletion polymorphism in thymidylate synthase gene. The analysis of polymorphisms for rs3918290, rs55886062, rs67376798 and 6-bp insertion/deletion in TYMS was done by Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCRRFLP) TYMS VNTR analysis. 5-FU-related toxicities such as anemia, febrile neutropenia, neurotoxicity, vomiting, nausea, and mucositis were evaluated according to NCI-CTC criteria version 4.0. T-test and chi-square were used and p-values less than 0.05 were considered statistically significant. RESULTS: DPYD gene polymorphisms were not observed in this study. The frequency of the TYMS +6 bp allele was 40.35% and the -6 bp allele was 59.65% in this study. The frequency of VNTR 2R allele was 48.75% and 3R allele was 51.15%. Toxicity grade II diarrhea, mucositis, nausea, vomiting, and neurotoxicity was 2.2, 24.1, 15.7, 6, and 51.8%, respectively. Thymidylate synthase ins/del polymorphisms were associated with increased grade III neurotoxicity (p=0.02). Furthermore, anemia grade III was significantly associated with 2R/2R genotype (0.009). CONCLUSION: Thymidylate synthase gene polymorphisms may play a key role in fluoropyrimidne -based chemotherapy. Although rare DPYD polymorphisms were not observed in our study, according to large population studies, DPYD gene polymorphisms could be used as a predictive biomarker for patient treatments.

Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a high-risk adverse drug reaction because of its associated risk of life- and limb-threatening thrombosis. Rivaroxaban may be considered as an ideal nonheparin anticoagulant alternative for the management of HIT. In this preliminary retrospective study, the efficacy and safety of rivaroxaban to control the clinically suspected HIT (4Ts score 4 points or greater) were evaluated. Patients with chronic kidney disease, hepatic impairment, mechanical heart valves, and active bleeding were excluded. Forty-two eligible patients who received rivaroxaban for clinically suspected HIT were evaluated by medical records review, with 12-month follow-up after the first dose of rivaroxaban. End points included confirmed thrombosis (primary end point), mortality, and adverse treatment-related events. HIT-associated thrombosis was found in 17/42 (40.5%) patients before receiving rivaroxaban. After rivaroxaban therapy, platelet counts normalized in all patients, with only 1/42 (2.3%) patients developing new thrombosis. No hemorrhagic event was recorded in the patients. Twelve patients (28.6%) died, but the cause of death was not related to the thrombosis, hemorrhage, or adverse effects of rivaroxaban. Our findings are consistent with the available emerging data, suggesting that rivaroxaban is a safe and effective drug for the management of clinically suspected HIT. Rivaroxaban is a particularly valuable treatment option in developing countries, where there are issues of cost and availability of approved alternative agents.

Personalized medicine in colorectal cancer.

Colorectal cancer (CRC) is a heterogeneous disease with various genetic and epigenetic factors leading to difficulties in response to both the therapy and drug resistance. Moreover, even in tumors with similar histopathological characteristics, different responses and molecular features could be observed because of the genetic basis and its interactions with the living environment. Through personalized medicine, we can classify patients into separate groups according to their genetic and epigenetic features and their susceptibility for a specific disease which could help with choosing the best therapeutic approach. In this review, genetic and epigenetic factors that cause heterogeneity in colorectal cancer are evaluated and proper drug administration in both chemotherapy and target therapy are suggested.

Association of interleukin-1 gene polymorphism with risk of gastric and colorectal cancers in an Iranian population.

BACKGROUND: Chronic inflammation is associated with neoplasms and several types of cancer. Therefore, polymorphisms in the inflammation-related genes could modify the cancer susceptibility. OBJECTIVE: To investigate the associations between IL-1RN VNTR and rs419598 polymorphisms in IL-1 receptor antagonist (IL-1ra) and colorectal cancer (CRC) and gastric cancer (GC) in an Iranian population. METHODS: In this study, 126 cancer cases (91 CRC and 35 GC) and 97 healthy controls were included. Genotyping of IL-1RN VNTR and rs419598 was performed by PCR amplification and PCR-RFLP, respectively. Logistic regression was applied to identify the independent risk factors for colorectal and gastric cancers by computing the odds ratio (OR) and 95% confidence intervals (95% CI). All statistical analyses were performed using the SPSS statistical software. RESULTS: There were significant differences between cancer groups and control group concerning the frequency of A1/A2 genotypes in IL-1RN VNTR polymorphism. The carrier status of IL-1RN* 2 allele was associated with increased risk of CRC (p = 0.0003; OR = 0.02; 95% CI: 0.491-0.85) and GC (p = 0.0006; OR = 0.106; 95% CI: 0.321-0.035). Also, the homozygous ILRN *2/*2 genotype was associated with increased risk of gastric cancer (p = 0.04; OR = 0.133; 95% CI: 0.020-0.908). There was no association between different alleles of rs419598 and CRC and GC. CONCLUSION: This study demonstrates an association between the carrier status of IL-1RN* 2 and CRC and GC in an Iranian population.

Content of Spiritual Counselling for Cancer Patients Undergoing Chemotherapy in Iran: A Qualitative Content Analysis

Background: Cancer is one of the leading causes of human death. Besides clinical treatment, cancer patients may need emotional and spiritual counselling to overcome their mental and morale problems. Such counselling sessions have been reported influential by many patients. We aimed to explore the structure of spiritual counselling sessions and their content as one of services provided to patients who experience chemotherapy in Iranian hospitals. Methods: Through a qualitative content analysis study, we recorded the discussions between a counsellor, who was a cleric as well, and cancer cases who were undergoing chemotherapy in a hospital in Tehran. The sessions were only recorded if the patient consented to attend at the study. All consideration were taken to avoid release of patients' identity. The recorded discussions were transcribed verbatim and analyzed thematically after each session, until no new theme was emerged. Result: Twenty two sessions were held. The patients aged 53 years old on average. The content of discussions were analyzed along which 165 codes emerged. Four general themes or phases were recognized through counseling as (i) history-Taking (including demographic, disease-related and spiritual history and characteristics), (ii) general advice, (iii) spiritual-religious advice, and (iv) dealing with patients' spiritual or religious ambiguities and paradoxes. Conclusion: Counselling of cancer patients needs special and in depth knowledge on spiritual and religious issues. The counsellor should be able to motivate patients, among whom many are disappointed, to follow the curative instructions well and stay hopeful about their treatment and life. Exploring and understanding what happens during a spiritual counselling session can counselling to the conformity and standardization of such interventions.

Successful Treatment of a Catheter-Induced Superior Vena Cava Syndrome through Catheter-Directed Thrombolysis: A Case Report.

Superior vena cava (SVC) syndrome is a medical condition resulting from the obstruction of the blood flow through the large central veins. Recently, central venous catheters have been reported as the increasingly common cause of this syndrome. We describe a 56-year-old woman with previous history of metastatic colon cancer, who had recently undergone central venous catheter insertion for her second chemotherapy course. Eight days following port insertion, she presented with signs and symptoms suggestive of acute SVC syndrome, which was successfully managed with catheter-directed thrombolysis. The pre-discharge transesophageal echocardiography and conventional angiography showed a patent SVC. The patient was discharged and remained asymptomatic over a 6-month follow-up. This case shows that catheter-directed thrombolysis may be used as a safe treatment for catheter-induced acute SVC syndrome in patients who have undergone catheter insertion in the central vein.

Colonic diverticular abscess presenting as chronic diarrhea: a case report.

INTRODUCTION: Several complications have been reported with diverticular disease of colon. Perforation of the diverticulum of colon may lead to development of abdominal abscesses which can have diverse manifestations. CASE PRESENTATION: This report describes a 72 year-old woman presented with a one month history of non-bloody diarrhea, abdominal pain, and low grade fever. Computed tomography scan confirmed presence of a large local air-fluid level within the culdesac area. Laparotomy revealed a large pelvic abscess which was surrounded between rectosigmoid and uterus with severe tissue necrosis of rectosigmoid colon and uterus. CONCLUSION: Although rarely reported, abdominal abscesses due to colonic diverticulitis may present as refractory chronic diarrhea.