Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review.

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell's nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC. SIGNIFICANCE STATEMENT: The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients.

Efficacy and safety of diphereline 11.25 mg, microrelin 11.25 mg, and microrelin 3.75 mg in premenopausal patients with breast cancer: a non-inferiority randomized clinical trial.

BACKGROUND: Diphereline is a Gonadotropin-Releasing Hormone agonist commonly used in patients with breast cancer. This study aimed to compare the efficacy and safety of one-month and three-month Microrelin injections produced by Homa Pharmed Company with three-month Diphereline injections manufactured by IPSEN, France. METHODS: The study was a non-inferiority randomized clinical trial conducted between 2019 and 2023 on premenopausal women candidates for endocrine therapy. The participants were randomly assigned in blocks of six to one of three groups named A (Diphereline 11.25 mg), B (Microrelin 11.25 mg), and C (Microrelin 3.75 mg). The participants' menopausal symptoms, estradiol, and FSH serum levels were recorded in three-month intervals for one year. The efficacy of each medication and its side effects were compared among the three groups by statistical analysis during the one-year follow-up. RESULTS: The study included 133 patients with breast cancer. A decreasing trend in the serum levels of FSH and estradiol and an increasing trend of menopausal symptoms were recorded during the study. No specific side effects leading to drug disruption, hospitalization, or exclusion from the study were observed. Adjusting the effect of study group and time showed no significant changes in estradiol levels between groups B (p = 0.506) and C (p = 0.607) and group A. Also, serum FSH changes between groups B (p = 0.132) and C (p = 0.104) compared to group A were not significant. Moreover, the menopausal symptoms during the one-year follow-up did not significantly increase in group B (p = 0.108) and C (p = 0.113) compared to group A. CONCLUSIONS: It can be concluded that injections of both Microrelin 11.25 mg and 3.75 mg, produced by Homa Pharmed, Iran, are non-inferior in terms of effectiveness and incidence of menopausal symptoms compared to Diphereline, manufactured by IPSEN, France. TRIAL REGISTRATION: IRCT.ir, IRCT20201227049847N1; Registered on 09/01/2021.

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.

Comparing the efficacy and side-effects of PDLASTA® (Pegfilgrastim) with PDGRASTIM® (Filgrastim) in breast cancer patients: a non-inferiority randomized clinical trial.

BACKGROUND: The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. METHODS: In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. RESULTS: Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. CONCLUSION: It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. TRIAL REGISTRATION: IRCT20190504043465N1 , May 2019.

Effects of synbiotic supplementation on serum adiponectin and inflammation status of overweight and obese breast cancer survivors: a randomized, triple-blind, placebo-controlled trial.

PURPOSE: Adipokines and inflammatory factors can affect breast cancer (BC) prognosis and recurrence among breast cancer survivors (BCSs). This study was to evaluate the effects of synbiotic supplementation along with a low-calorie diet on some recurrence-related factors such as adiponectin, tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) among obese and overweight BCSs. METHODS: We performed a randomized, triple-blind, placebo-controlled clinical trial among 76 overweight or obese postmenopausal women with a history of hormone-receptor-positive BC. Participants were randomly divided into 2 groups to intake either 109 CFU/day synbiotic supplement or placebo (n = 38 each group) for 8 weeks. All participants were given a low-calorie diet program. The primary outcome was serum concentration of adiponectin which was measured at baseline and after 8 weeks. RESULTS: Compared with the placebo, synbiotic intake significantly increased adiponectin (+ 13.58 (10.08, 18.17) vs. - 0.42 (- 2.90, 1.98) µg/ml; P < 0.001). In addition, synbiotic supplementation resulted in significant reduction in TNF-α levels (- 17.09 (- 32.05, - 13.60) vs. 0.20 (- 3.97, 2.00) ng/L; P < 0.001) and hs-CRP levels (- 1.14 (- 1.90, - 0.88 vs. - 0.06 (- 0.38, 0.15) mg/L; P < 0.001) compared with the placebo. CONCLUSIONS: In conclusion, 8-week synbiotic consumption by overweight and obese postmenopausal BCSs had beneficial effects on adiponectin, TNF-α, and hs-CRP. TRIAL REGISTRATION: IRCT, IRCT20091114002709N49. Registered 18 May 2018, http://www.irct.ir : IRCT20091114002709N49.

The impact of hormone receptor status on survival and recurrence of HER2-positive breast cancers in standard adjuvant setting: A retrospective study in Tehran, Iran.

Objectives: To evaluate hormone receptor status on survival and recurrence of the human epidermal growth factor receptor 2-positive breast cancer treated with Trastuzumab in the adjuvant setting. METHODS: The retrospective study was conducted in 2017 at the Breast Cancer Research Centre, Tehran University of Medical Sciences, Tehran, Iran, and comprised data of women aged >20 years with stage I-III of human epidermal growth factor receptor 2-positive breast cancer who were treated with Trastuzumab from 2008 to 2017. The patients were divided into two groups. Group P had patients who were triple positive for human epidermal growth factor receptor 2, oestrogen receptor and progesterone receptor. Group N had patients positive for only human epidermal growth factor receptor 2. All patients in group P were treated with hormone therapy. Overall survival, disease-free survival, and distant metastasis rates were measured. SPSS 22 was used for data analysis. RESULTS: Of the 263 patients, 169(%) were in group P with a mean age of 46.86 ± 10.92 years, and 94(%) were in group N with a mean age of 48.53±12.33 years (p>0.05). There were no unfavourable predictors for overall survival and disease-free survival except for stage (p<0.05). The difference on both counts between the groups was not significant (p>0.05 each). CONCLUSIONS: The impact of hormone receptor positivity on survival and progression of human epidermal growth fac tor receptor 2-positive breast cancer remains an area of debate.

Randomized Study of the Effect of Dietary Counseling During Adjuvant Chemotherapy on Chemotherapy Induced Nausea and Vomiting, and Quality of Life in Patients With Breast Cancer.

Patients with breast cancer (PsBC) usually face with chemotherapy induced nausea and vomiting (CINV). The aim of this study was to assess the impact of nutritional counseling on CINV and quality of life (QoL) of PsBC. 150 PsBC were randomly assigned for receiving a personalized diet, which contained 1.2-1.5 g/kg of protein, 30% of energy from fat and 55-60% of energy from carbohydrate, a face to face nutrition education, and a pamphlet which contained beneficial nutrition information to reduce the severity of CINV before each chemotherapy session for three times (n = 75) or regular care (n = 75). CINV, QoL, and dietary intake were evaluated after each chemotherapy session. Nausea rating index, overall nausea index, and visual analog scale (P < 0.001) were dramatically lower in the intervention group. Global health status/QoL as well as physical functioning, role functioning, emotional functioning, and cognitive functioning (P < 0.001) were significantly better in the intervention group. Patients in the control group experienced more fatigue, nausea and vomiting, pain, dyspnea, loss of appetite, constipation, and diarrhea (P < 0.001). Nutrition counseling during adjuvant chemotherapy among PsBC reduced the occurrence of CINV and led to significant improvements in the QoL.

The Effect of Dietary Intervention Along with Nutritional Education on Reducing the Gastrointestinal Side Effects Caused by Chemotherapy Among Women with Breast Cancer.

Gastrointestinal (GI) side effects caused by chemotherapy in women with breast cancer are common but poorly understood which might be controlled by nutritional intervention. Thus, the major aim of this study was to assess the effect of dietary intervention along with nutritional education on reducing these side effects. The present study is a single-center, single-controlled, and randomized trial. A total of 150 patients with breast cancer undergoing chemotherapy were randomly assigned into intervention group to receive dietary intervention and nutritional education (n = 73) or control group (n = 67) for 10 weeks, after their three sessions of chemotherapy. The primary endpoint was the GI symptoms after each session of chemotherapy that were measured by a designed questionnaire based on ROMIII questionnaire. The severity of GI side effects in the dietary intervention along with nutritional education was decreased significantly in the third session of chemotherapy compared to the first session, which include reflux disorder (P = 0.05), anorexia (P < 0.001), nausea (P = 0.002), constipation (P < 0.001), and diarrhea (P < 0.001). Moreover, significant reductions were observed in the severity of GI side effects in the intervention group compared to control group after the third session (P < 0.001). After adjusting the analysis for baseline values including age, job, education level, weight, and body mass index, significant changes were observed for GI side effects in the intervention group compared to the control group (P < 0.001). This study showed beneficial effects of individualized dietary intervention along with nutritional education on reducing diarrhea, constipation, vomiting, and nausea in women with breast cancer during the chemotherapy.

Prognostic factors influencing prognosis in early breast cancer patients.

AIM OF THE STUDY: The present study showed the clinicopathological characteristics and survival of early breast cancer (BC) patients. MATERIAL AND METHODS: A total of 236 patients were included in the study. The mean follow-up time was 59.5 months (range: 12-204 months). The inclusion criteria consisted of female patients aged > 20 years and early BC patients (stages I and IIA). RESULTS: The mean age at diagnosis was 51.2 years (range, 23-83 years), and 55.9% of patients were aged ≥ 50 years. Most patients (92.8%) did not have lymph node metastasis, and luminal B had the highest prevalence (54.2%) in patients. The eight-year overall survival (OS) and disease-free survival (DFS) rates were 98.3% and 92.3%, respectively. Stage IIA and Ki67 index ≥ 14% were more prevalent in the patients with tumour size of 2 ≤ T ≤ 5 cm compared to another tumour size group and Ki67 index. CONCLUSIONS: The mean age at diagnosis in this study was in agreement with other studies reported in various areas, but with a higher percentage for elderly patients compared to some previous studies. In addition, the survival rate in the present study was higher than the results of previous studies. Future studies need to investigate these factors in a higher number of patients and in different areas and should select similar stages for early BC.

The comparison of anthracycline-based and non-anthracycline-based regimens in adjuvant chemotherapy of HER2-positive non-metastatic breast cancers.

AIM OF THE STUDY: This study aimed to assess the efficacy of anthracycline-based (AB) and non-anthracycline-based (nAB) adjuvant therapies in the human epidermal growth factor receptor 2 (HER2)-positive non-metastatic BC (nMBC) patients. MATERIAL AND METHODS: This retrospective study included women with HER2-positive BCs (stage I-III) treated with trastuzumab from 2008 to 2017. The patients were divided into two groups, including 196 patients in group AB and 67 in group nAB. RESULTS: Cox's proportional hazard regression analysis showed no unfavourable predictors for five-year overall survival (OS) and disease-free survival (DFS) except for stage and hormone therapy. The OS rate was 67.9% in group AB and 80.6% in group nAB (p = 0.630). The DFS rate was 61.6% in group AB compared with 67.1% in group nAB (p = 0.447). CONCLUSIONS: The results showed no difference between the efficacies of AB and nAB regimens in HER2-positive nMBCs in adjuvant setting. Therefore, selecting the nAB regimen can reduce the serious damage caused by the AB regimen.

Phase II study of adjuvant docetaxel and carboplatin with/without doxorubicin and cyclophosphamide in triple negative breast cancer: a randomised controlled clinical trial.

AIM OF THE STUDY: The aim of this trial was to compare overall survival (OS), disease-free survival (DFS), and toxicity of two adjuvant regimens in triple negative patients with Iranian ethnicity. MATERIAL AND METHODS: In a phase II trial, patients with previously untreated triple negative breaststroke cancer were randomly assigned by using docetaxel 70 mg/m2 and carboplatin AUC = 7 every three weeks with granulocyte colony-stimulating factor for sin courses (arm A) or doxorubicin hydrochloride 60 mg/m2 and cyclophosphamide 600 mg/m2 every three weeks with G-CSF for four courses followed by docetaxel 70 mg/m2 and carboplatin AUC = 7 every three weeks with G-CSF for four courses (arm B). RESULTS: A total of 119 patients were randomly enrolled in our study (60 patients in Arm A and 59 patients in Arm B) between 2011 and 2016. The mean follow-up was 40 months at the time of treatment analysis. The 2-year and 5-year DFS rates for Arm A were 92.7% vs. 85% and for Arm B were 82.6% vs. 64.4%. The 2-year and 5-year OS rates for Arm A were 96.5% vs. 91.7% and for Arm B were 90.5% vs. 81.3%. There was a significant correlation for DFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. CONCLUSIONS: In our research, less progression was found with Arm A as compared to Arm B. Adding of anthracyclines such as doxorubicin hydrochloride did not increase OS and DFS in triple negative breast cancer (TNBC) patients.

Refractory and Recurrent Idiopathic Granulomatous Mastitis Treatment: Adaptive, Randomized Clinical Trial.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is mostly described as an autoimmune disease with higher prevalence among Middle Eastern childbearing-age women. This study aimed to evaluate the best treatment of choice in patients with resistant or recurrent IGM. STUDY DESIGN: Patients with established recurrent or resistant IGM who were referred to the Breast Cancer Research Center from 2017 to 2020 were randomly assigned to either one of the following treatment groups: A (best supportive care), B (corticosteroids: prednisolone), and C (methotrexate and low-dose corticosteroids). This adaptive clinical trial evaluated radiological and clinical responses, as well as the potential side effects, on a regular basis in each group, with patients followed up for a minimum of 2 years. RESULTS: A total of 318 participants, with a mean age of 33.52 ± 6.77 years, were divided into groups A (10 patients), B (78 patients), and C (230 patients). In group A, no therapeutic response was observed; group B exhibited a mixed response, with 14.1% experiencing complete or partial responses, 7.7% maintaining stability, and 78.2% experiencing disease progression. Accordingly, groups A and B were terminated due to inadequate response. In group C, 94.3% achieved complete response, 3% showed partial remission, and 2.7% had no response to therapy. Among the entire patient cohort, 11.6% tested positive for antinuclear antibodies, 3.5% for angiotensin-converting enzyme, and 12.3% for erythema nodosum. Notably, hypothyroidism was a prevalent condition among the patients, affecting 7.2% of the cohort. The incidence of common side effects was consistent across all groups. CONCLUSIONS: The most effective treatment option for patients with recurrent or resistant IGM is a combination therapy involving steroids and disease-modifying antirheumatic drugs such as methotrexate.

Non-thermal CO2 Laser Therapy (NTCLT): A Novel Photobiomodulative Approach for Immediate Pain Relief of Patchy Oral Mucositis Due to Chemotherapy of Solid Tumors.

Introduction: Chemotherapy-induced oral mucositis (COM) is a prominent complication of chemotherapy (CT). Non-thermal CO2 laser therapy (NTCLT) has been demonstrated as an innovative and safe photobiomodulative approach in some kinds of painful oral lesions. The purpose of this study was to evaluate the palliative effects of one session of NTCLT on COM lesions. Methods: Patients with painful COM (WHO grade:≥2) were included in this before-after clinical trial based on the eligibility criteria. The oral lesions were irradiated with a CO2 laser (power: 1 W, scanning the lesions with the rapid circular motion of the defocused handpiece) through a thick layer (3-4 mm) of a transparent gel containing a high-water content. The severity of pain in the lesions was self-assessed using a 0-to-10 visual analogue scale (VAS) for 7 consecutive days. The evaluating physician visited the patients on the 3rd and 7th days in search of any kind of complications. Results: Seventeen adult patients with 35 patches of OM due to chemotherapy of solid tumors completed the trial. Immediately after NTCLT, the mean for non-contact VAS pain scores of the lesions significantly declined from 4.91±2.356 to 0.29±0.622 (P<0.001) and the mean for contact VAS pain scores from 7.77±1.57 to 1.31±1.18 (P<0.001). The mean VAS pain scores of the lesions showed statistically significant differences between the follow-up periods compared to the baseline (P<0.001). The process was completely pain-free and required no anesthesia. After NTCLT, no kind of thermal adverse effects such as irritation, destruction, aggravation and even erythema were observed. Conclusion: Based on the results of this before-after clinical trial, NTCLT has the potential to be considered as a non-invasive and safe palliative option for the pain management of patchy OM due to chemotherapy of solid tumors.

Preferences of Patients With HR+ and HER2- Breast Cancer Regarding Hormonal and Targeted Therapies in the First Line of Their Metastatic Stage: A Discrete Choice Experiment.

OBJECTIVE: Some hormonal and targeted treatment options are available in the first line of metastatic HR+ & HER2- breast cancer. This study aimed to quantify the preferences of Iranian breast cancer patients regarding the levels of attributes of hypothetical treatment options. METHODS: The discrete choice experiment included 16 orthogonally designed scenarios. A novel method (named "the World Cup") was used to offer the scenarios to the respondents. Each choice task had 2 hypothetical treatments. A conditional logit regression model was used to obtain preference estimates, based on an expected utility model without interactions between attributes. RESULTS: A total of 78 patients with breast cancer participated in the survey. The effectiveness was the main concern of the patient, which was followed by monthly cost. Participant patients significantly preferred to avoid adverse events; preference dummy-coded estimates were reported. CONCLUSION: Followed by the effectiveness and cost, the risk of neutropenia, stomatitis, and arthralgia was least prioritized by the respondents. The estimation for the levels of the attribute "administration mode" is not significant (P = .690). Patients with breast cancer were willing to pay significant amounts to gain the benefit of the treatments and showed a significant willingness to accept to avoid the adverse events of the treatments.

The effect of synbiotic on glycemic profile and sex hormones in overweight and obese breast cancer survivors following a weight-loss diet: A randomized, triple-blind, controlled trial.

BACKGROUND: The investigation was designed to assess the effects of synbiotic supplementation on glycemic profile, insulin-like growth factor-1 (IGF-1) and sex hormones in overweight and obese postmenopausal breast cancer survivors (BCSs) who had hormone-receptor-positive breast cancer. METHODS: This randomized, triple-blind, placebo-controlled trial was conducted on 76 overweight and obese BCSs aged 57.43 (5.82) years. All participants were given a specified low calorie diet and were randomly assigned into two groups to intake 109 CFU/day of synbiotic supplement (n = 38) or placebo (n = 38) for 8 weeks. Body composition, physical activity, glycemic profile, IGF-1, estradiol, testosterone and dehydroepiandrosterone sulfate (DHEA-S) were measured at baseline and after 8 weeks. RESULTS: A significant reduction in serum insulin (median change (Q1, Q3) from baseline of -1.05 (-2.36, 0.32) µIU/mL; P = 0.006) and insulin resistance (HOMA-IR) (mean change (SD) from baseline of -4.0 (0.9); P = 0.007) were seen over the 8 weeks in the synbiotic group. However, no significant changes were observed in serum insulin, fasting plasma glucose, HbA1c, HOMA-IR, IGF-1, estradiol, testosterone, DHEA-S and sex hormone binding globulin between-groups at the end of the intervention. CONCLUSIONS: Overall, as the 8-week synbiotic consumption compared with placebo had insignificant-reducing effects on glycemic profile, IGF-1 and sex hormones among overweight and obese postmenopausal BCSs, synbiotics may exert considerable beneficial consequences, which need to be further assessed in future clinical trials. TRIAL REGISTRATION: IRCT, IRCT2015090223861N1. Registered 02 February 2017, http://www.irct.ir: IRCT2015090223861N1.

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). METHODS: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements. FINDINGS: A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm. IMPLICATIONS: The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.

The Incidence of Deep Vein Thrombosis in Breast Cancer Patients Receiving Outpatient Cancer Therapy in Iran.

BACKGROUND: Venous thromboembolism (VTE) is one of the main causes of mortality in patients with cancer. This study was conducted to assess the incidence of deep vein thrombosis (DVT) in breast cancer patients receiving outpatient cancer therapy. MATERIALS AND METHODS: This multi-center prospective cohort study was conducted on patients with breast cancer, initiating an outpatient chemotherapy regimen in five medical centers in Iran. Eligible patients were enrolled in the study consecutively between January 2013 and January 2015. The primary outcome was lower extremity DVT based on duplex/doppler ultrasonography two months after the first course of chemotherapy (visit 2) and after the end of the course (visit 3). All patients were followed-up from the onset of chemotherapy until the first occurrence of lower extremity DVT, death, or the end of the course. RESULTS: A total of 427 eligible breast cancer patients were recruited in the study, 403 of whom attended at least one follow-up visit. The mean (SD) duration of follow-up was 4 (1.3) months. During the follow-up, only one patient showed DVT on duplex/doppler ultrasonography in visit 2. Therefore, the two-month and overall cumulative incidence risk of DVT was 0.25% (95% CI: 0.00-0.74%). However, the mean D-dimer level showed no significant change (P>0.05). CONCLUSION: Our findings showed the low risk of DVT in breast cancer patients receiving outpatient cancer therapy.

Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin.

AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti-endomysial antibody (EMA) and tissue transglutaminase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE patients was 34.6 +/- 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3, 12 had Marsh 2, and 2 had Marsh 1 lesions. The severity of anemia was in parallel with the severity of duodenal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 +/- 1.6 to 12.8 +/- 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 +/- 1.1 to 13.1 +/- 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.

Effect of Ginger and Chamomile on Nausea and Vomiting Caused by Chemotherapy in Iranian Women with Breast Cancer.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) places a significant burden on the patient. Herbal agents are the most commonly complementary therapies used among the public. This study was done to determine the effect of ginger and chamomile capsules on nausea and vomiting in cases undergoing chemotherapy for breast cancer (BC). MATERIALS AND METHODS: In a randomized, double-blind and clinical trial study, 65 women with BC undergoing chemotherapy were referred to Breast Cancer Research Center, Tehran, Iran, between May 2013 to June 2014. Regimen for ginger group for 5 days before and 5 days after chemotherapy was: 2 times a day and 500 mg capsules of powdered ginger root in addition to a routine antiemetic regimen consisting of dexamethasone, metoclopramide and aprepitant (DMA) capsules. Chamomile group similarly was: 2 times a day and 500 mg capsules of Matricaria chamomilla extract in addition to a routine antiemetic regimen consisting of DMA capsules. Control group, routine antiemetic regimen consisting of DMA capsules. RESULTS: There were no significant differences between the ginger, chamomile and control groups regarding age. Drugs used for chemotherapy were identical and duration of disease was also matched (1-4 months). Ginger and chamomile were both significantly effective for reducing the frequency of vomiting, there being no significant difference between the ginger and chamomile groups. Moreover, unlike the chamomile, ginger significantly influenced the frequency of nausea. CONCLUSIONS: According to the findings of this study, it should be declared that taking ginger capsules (1 g/day) might relieve CINV safely. Nurses dealing directly with cancer patients should be responsible for providing educational programs for patients and their families about how to deal with their drug regimens and associated side effects.

Phase III of Study of R-CHOP-21 vs R-CHOP-14 for Untreated Stage III and IV B-cell Non-Hodgkin's Lymphoma: a Report from Iran.

BACKGROUND: A combination of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat B-cell non-Hodgkin's lymphoma (NHL). The aim of this trial was to evaluate overall survival (OS), progression free survival (PFS) and toxicity of R-CHOP-14 compared to R-CHOP-21 in untreated stage III and IV B-cell NHL patients with Iranian ethnicity. MATERIALS AND METHODS: In a phase III trial, patients with previously untreated stage III and IV indolent and aggressive B-cell NHL were randomly assigned by using a minimization method to receive six to eight cycles of either R-CHOP-21 (administered every 21 days) or R-CHOP-14 (administered every 14 days with granulocyte colony-stimulating factor). RESULTS: A total of 143 patients were randomly enrolled in our study (66 patients in R-CHOP-14 group and 77 patients in R-CHOP-21), between 2011 and 2014. The mean follow-up was 45 months at the time of treatment analysis. The 2-year and 5-year PFS rates for the R-CHOP-14 group were 83.6% vs 73.6% and for R-CHOP-21 group were 75% vs 54%. The 2-year and 5-year OS rates for R-CHOP-14 group were 98% vs 89% and for R-CHOP-21 group were 84.4% vs 67.5%. There was a significant correlation for PFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. CONCLUSIONS: In our research improved survival was found with CHOP-14 as compared to CHOP-21. It is possible that drug metabolism in different races/ethnicities may be one important factor.