Assessment of thyme honey oral gel for the prevention of adriamycin and cyclophosphamide chemotherapy-induced oral mucositis in patients with breast cancer.

PURPOSE: Oral mucositis (OM) is a common complication of cancer treatment that has an impact on a patient's quality of life and the outcome of cancer therapy. This trial evaluated the effect of thyme honey oral gel for the prevention of chemotherapy-induced OM. METHODS: One hundred ten breast cancer patients who received their first cycle of chemotherapy with adriamycin (60 mg/m2) and cyclophosphamide (600 mg/m2) were randomly recruited into two groups: group A were patients who followed general oral hygiene recommendations and rinsing saline 3 times a day, and group B were patients with similar protocol but supplied with our formulated oral gel to be applied 2 to 4 times a day. Patients were assessed by the World Health Organization (WHO) oral mucositis grading scales and self-assessment daily questionnaire. RESULTS: The use of thyme honey was associated with diminishing incidence of OM grade ≥ 2 (95% CI, 0.12 to 0.90; P = 0.030), duration of OM (- 3.36 days; 95% CI, - 5.50 to - 1.22; P = 0.037) and delayed occurrence of OM grade ≥ 2 (95% CI, 0.10 to 0.80; P = 0.017). CONCLUSION: Thyme honey can be considered as a prophylactic agent for OM and decrease the severity of its symptoms. TRIAL REGISTRATIONS: This protocol was registered at the Iranian Registry of Clinical Trials: registration number IRCT201506063106N25, on June 12, 2015; approved by the institutional review board at the Deputy of Research, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; and approved by the Ethics Committee of Medical Researches of Pharmaceutical Sciences Branch of Islamic Azad University, Tehran, Iran-reference number 5936, on August 17, 2014.

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.

Evaluation of urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 as biomarkers of renal function in cancer patients treated with cisplatin.

INTRODUCTION: Cisplatin-associated acute kidney injury (AKI) is the major limitation to the use of cisplatin-based chemotherapy regimens. Serum creatinine as a traditional marker did not increase in a timely enough fashion in AKI patients. Therefore, recently, the novel markers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were considered for early detection of AKI. The aim of this study was to compare the sensitivity and specificity of urinary NGAL and KIM-1 with serum creatinine in cisplatin related AKI. METHODS: Patients ≥18 years with solid tumors who received cisplatin-based chemotherapy were included. Urine samples were collected 0, 6 and 24 h after cisplatin infusion and the urinary NGAL, KIM-1, and creatinine concentrations were evaluated. NGAL and KIM-1 concentrations were adjusted based on urine creatinine to eliminate hydration effects. Serum creatinine levels were assessed at the base and 72 h after cisplatin administration. RESULTS: Seven out of the 35 recruited patients (20%) suffered from AKI defined by Acute Kidney Injury Network criteria. In AKI patients, the ratio of urinary KIM-1-creatinine at 24 h compared to baseline (24 h/baseline) and NGAL-creatinine 24 h/baseline were significantly higher than those of non-AKI group (p = 0.037 and 0.047 respectively). The area under the receiver-operating characteristic curve for KIM-1-creatinine 24 h/baseline and NGAL-creatinine 24 h/baseline were 0.78 (0.59-0.96, p = 0.032) and 0.77 (0.57-0.97, p = 0.036) respectively. CONCLUSIONS: Our findings showed that the changes in urinary NGAL-creatinine and KIM-1-creatinine ratios, 24 h after cisplatin administration can be utilized to predict AKI in cisplatin recipients.

Appropriateness of using granulocyte colony-stimulating factor (G-CSF) for primary prophylaxis of febrile neutropenia in solid tumors.

INTRODUCTION: Febrile neutropenia (FN) is one of the dose-limiting adverse effects of chemotherapy. Granulocyte-Colony Stimulating Factors (G-CSFs) minimize the incidence of FN and reduce the risk of neutropenia complications. This study was conducted to address the prescription pattern of G-CSF for primary prophylaxis of FN during the first cycle of chemotherapy in solid tumors. METHOD: This prospective observational study was done to investigate the G-CSF prescription pattern in patients receiving the first cycle of chemotherapy for solid tumors and compare it with the NCCN guideline recommendations. RESULT: Based on the guideline, prophylactic G-CSF administration was indicated in 26 of the 96 patients (27.1%) and all of them received G-CSF. On the other hand, 70 patients (72.9%) did not meet the guideline criteria for prophylaxis, but 60 (62.5%) of them received G-CSF. Seven doses of pegfilgrastim and 165 doses of filgrastim were used inappropriately in the study population, which was associated with an economic burden of about 224.7 million IRR (5350 USD). CONCLUSION: Taken together, inconsistencies with the guideline were observed in this prospective evaluation, suggesting that submitting rationalized policies to decrease G-CSF prescription, especially in patients with a lower or intermediate FN risk, yields substantial cost savings.

Association between Ki-67 expression and clinicopathological features in prognosis of breast cancer: A retrospective cohort study.

BACKGROUND: Breast cancer is the most common diagnosed female cancer. Breast cancer is also the leading cause of cancer death in females accounting for 13.7% of female cancer-related mortality globally. Variable known prognostic factors such as histological tumor type, tumor size, nodal status, grade, age, and estrogen receptor (ER) status and the proliferation marker - Ki-67 influence the type of treatment decision. The purpose of this present study is to investigate the association between Ki-67 expression with several clinicopathological variables and patients' outcome. MATERIALS AND METHODS: This is a retrospective cohort study from September 2008 to March 2017; 165 newly diagnosed breast cancer patients were enrolled in the study. Ki67 levels were measured using immunohistochemistry and compared with clinicopathological variables. The relation of Ki67 expression with disease-free survival (DFS) and overall survival (OS) was also analyzed. RESULTS: The result of this study revealed that age, tumor size, menopausal status, and human epidermal growth factor receptor 2 (HER2) status had no effect on the patients' outcome. Patients with ER-positive, progesterone receptor (PR)-positive, and HER2-negative tumors expressed a higher rate of Ki-67 (>10%) than patients with ER-negative, PR-negative, and HER2-positive tumors, respectively. However, we found that Ki-67 levels were not significantly increased statistically with ER, PR, and HER2 statuses. There was a statistically significant correlation between Ki-67 expression and with higher stages of the disease. Multivariate analysis showed that Ki-67 expression could not to be an independent prognostic factor for 5-year OS and DFS. Furthermore, p53 status was only prognostic factor for 5-year OS whereas higher stages of disease and p53 status were prognostic factors for 5-year DFS. CONCLUSION: Ki67 could not be an independent variable for prediction of breast cancer outcome.

Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment.

Comparison of Three Fixation Methods for Femoral Neck Fracture in Young Adults: Experimental and Numerical Investigations.

Femoral neck fractures in young patients are usually caused by a high-energy trauma, which results in a perpendicular fracture. Although efforts are focused on preserving the femoral head in young patients, vertical femoral neck fracture is a problematic orthopedic injury due to the domination of shear forces. Due to controversy regarding which fixation method is the best choice, the purpose of this study was to find the most stable fixation method for this kind of fracture. This study includes experimental testing on cadaveric bone samples and finite element analysis (FEA) for three fracture fixation techniques, namely cannulated screws (CSs), dynamic hip screw with derotational screw (DHS + DS), and proximal femoral locking plate (PFLP). Experimental results of bone-implant stiffness, average femoral head displacement, failure load, failure energy, and relative position of the fractured fragments indicate that DHS + DS offers the strongest structure for stabilizing a vertical femoral neck fracture. Experimental data and FEA results both indicate that under static loading, the DHS + DS method of fixation produces the lowest femoral head displacement and interfragmentary movement, followed by PFLP and then CSs. The results of this research suggest that, based on the clinical assumption that a restricted weight-bearing regimen is recommended in the postoperative rehabilitation protocol, the DHS + DS method of fixation is a better choice compared to CSs and PFLP for a vertical femoral neck fracture fixation in young adults.

Estimating the treatment effect in patients with gastric cancer in the presence of noncompliance.

AIM: In this study, these methods were used to estimate the treatment effect in patients with gastric cancer in the presence of noncompliance. BACKGROUND: In medical sciences, simple and advanced methods are used to estimate treatment effects in the presence of noncompliance. METHODS: This historical cohort study surveyed 178 patients with gastric cancer underwent chemotherapy alone (chemotherapy alone group) and 193 patients underwent surgery and chemotherapy (surgery plus chemotherapy group) from 2003 to 2007 at the Cancer Institute of Imam Khomeini Hospital (Tehran). Demographic and clinical characteristics were extracted from patients' hospital records. The survival of patients was calculated as being from diagnosis to death or to the end of the study. The treatment effect was estimated using three methods: treatment as a time-dependent covariate, IPCW, and Structural Nested Models using STATA and R software. RESULTS: Fifty-six patients (31.5%) who underwent chemotherapy and 69 patients (35.8%) who underwent surgery and chemotherapy died by the end of the study. The hazard ratio in group I compared to group II was estimated between 1.5 to 2.07 times based on the simple analysis method. The modified hazard ratio was estimated to be 1.21 (95% CI: 1.11-1.32) based on the SNM method. Surgery plus chemotherapy is superior to chemotherapy alone, and it improves the overall survival (OS) rate of gastric cancer patients. CONCLUSION: Survival was improved in patients undergoing chemotherapy and surgery together compared to those undergoing chemotherapy alone. The results of the current study suggest that treatment effect can be estimated unbiasedly using the appropriate method.

Down-regulation of immune checkpoints by doxorubicin and carboplatin-containing neoadjuvant regimens in a murine breast cancer model.

OBJECTIVES: Immune checkpoint expression on tumor-infiltrating lymphocytes (TILs) has a correlation with the outcome of neoadjuvant chemotherapy (NAC) in breast cancer. However, the reciprocal effect of these regimens on the quality and quantity of immune checkpoints has hitherto not been addressed. We aimed to evaluate the impact of three NAC regimens on TILs and immune checkpoints in a murine triple-negative breast cancer model. MATERIALS AND METHODS: Syngeneic model of locally-advanced breast cancer was established in immunocompetent mice using a 4T1 cell line. Tumor-bearing animals were treated with human-equivalent dosages of doxorubicin, paclitaxel, paclitaxel and carboplatin combination, and placebo. Infiltration of CD3+, CD8+, and FoxP3+ cells into the tumor was assessed by immunohistochemistry. Expression of immune checkpoints, including PD-1, CTLA-4, and TIM-3, was evaluated by real-time PCR. RESULTS: Doxorubicin led to a significant (P<0.01) increase in the percentage of the stromal infiltrating CD3+ and CD8+ lymphocytes. Doxorubicin also suppressed significantly (P<0.05) the relative expression of PD-1 compared with the placebo. PD-1 expression was significantly (P<0.05) lower in the group treated with paclitaxel and carboplatin combination as compared with the placebo. The relative expression of TIM-3 was significantly (P<0.05) suppressed in doxorubicin-treated mice in comparison with other interventions. CONCLUSION: Our findings hypothesize that NAC with doxorubicin may potentiate antitumor immunity not merely by recruitment of TILs, but via down-regulation of PD-1 and TIM-3 checkpoints. Carboplatin-containing NAC may suppress PD-1 as well.

The Effect of Metformin on Survival Outcomes of Non-Metastatic Breast Cancer Patients with Type 2 Diabetes.

BACKGROUND: There are still inconsistencies about the role of metformin on breast cancer. This study was designed to assess metformin's effect on the prognosis of female breast cancer patients with type II diabetes. METHODS: The present research was carried out as a retrospective cohort study between 2003 and 2014. Breast cancer patients with pre-existing type II diabetes mellitus were included. Overall survival (OS) and relapse-free survival (RFS) were measured as the main endpoints. Kaplan-Meier estimate was used to calculate survival rates. RESULTS: 217 patients were included with a mean age of 53.32±11.10 years. 148 (68.2%) patients were prescribed metformin and 69 (31.8%) took other antidiabetic drugs (non-metformin group). Five-year OS and RFS rates for all patients were 82.5% (95% CI: 76.0%-87.4%) and 71.1% (95% CI: 64.2%-77.0%) respectively. Log-rank test showed that the metformin group had a significant advantage over the non-metformin group in terms of both OS and RFS rates (p.

Chemotherapy effect on daytime sleepiness and contributing factors in older adults with cancer.

OBJECTIVES: The objective of this study was to determine the prevalence of excessive daytime sleepiness (EDS) among older Iranian patients with cancer and to analyze the effect of chemotherapy treatment on patients' sleep problems. The relationship between sleep disturbances and physical activity, psychological factors, and demographic data, are also explored. METHODS: This cross-sectional study consisted of interviews with 83 patients, >60 years old with a solid tumor, carried out in Cancer Institute of Iran once prior to receiving chemotherapy and the second time after the first cycles of chemotherapy. Questionnaires consisted of demographic data, Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and Eastern Cooperative Oncology Group performance status (ECOG PS). Medical data were also gathered from hospital records. Logistic regression was used to identify predictors of excessive daytime sleepiness after chemotherapy. RESULTS: The results showed a significant association between EDS and receiving chemotherapy. 8.1% were initially experiencing EDS which increased to 21.6% after chemotherapy (P-value < .001). Anxiety before chemotherapy and number of regions of recurrence of cancer, if any, were identified as independent predictors of daytime sleepiness. CONCLUSIONS: As EDS prevalence increases after chemotherapy, and this can affect patients' quality of life and treatment outcomes; caregivers should bear in mind that senior patient with cancer, especially those suffering from anxiety and cancer recurrence, need special attention before starting treatment in order to manage EDS over the course of chemotherapy.

Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial.

BACKGROUND: The role of microRNAs (miRs) in hormone therapy (HT) is of keen interest in developing biomarkers and treatments for individuals with breast cancer. Although miRs are often moderate regulators under homeostatic conditions, their function is changed more in response to physical activity. OBJECTIVE: This single-blind randomized trial aimed to explore the effect of high-intensity interval training (HIIT) on serum levels of miRs in individuals with early-stage breast cancer undergoing HT. METHODS: Hormone receptor-positive women with breast cancer and healthy women were randomly assigned to a healthy control group (n=15), healthy group with HIIT (n=15), breast cancer group with HT (HT, n=26), and breast cancer group with HT and HIIT (HT+HIIT, n=26). The exercise groups underwent interval uphill walking training on a treadmill 3 times a week for 12weeks. At the end of the study, we analyzed changes in levels of cancer-related miRs (oncomiRs) and tumour suppressor miRs (TSmiRs) in response to the HT and HIIT. RESULTS: In women with breast cancer versus healthy controls, the expression of some oncomiRs was significantly increased - miR-21 (P<0.001), miR-155 (P=0.001), miR-221 (P=0.008), miR-27a (P<0.001), and miR-10b (P=0.007) - and that of some TSmiRs was significantly decreased - miR-206 (P=0.048), miR-145 (P=0.011), miR-143 (P=0.008), miR-9 (P=0.020), and let-7a (P=0.005). Moreover, HT considerably downregulated oncomiRs and upregulated TSmiRs. HIIT for 12weeks with HT significantly decreased the expression of the oncomiRs and significantly increased that of the TSmiRs as compared with HT alone. CONCLUSIONS: HITT could amplify the decrease and/or increase in expression of miRs associated with HT in women with breast cancer. A prospective trial could determine whether the use of circulating miRs for monitoring treatment can be useful in therapy decisions. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (No.: IRCT201202289171N1).

High-intensity interval training can modulate the systemic inflammation and HSP70 in the breast cancer: a randomized control trial.

OBJECTIVE: Exercise training is recently considered as a trend in adjuvant therapies for cancer patients, but its mechanisms need to be scrutinized further. This study is aimed to test the hypothesis that the patients who perform the high-intensity interval exercise training (HIIT) during hormone therapy would show improvements in low-grade inflammation and HSP70 compared to the controls receiving standard care. METHODS: Fifty two non-metastatic and hormone-responsive breast cancer patients were randomly assigned to high-intensity interval exercise (HIIT) (n = 26) and usual care (n = 26) groups. The HIIT groups participated in a high-intensity interval training protocol on a treadmill 3 days/week for 12 weeks. The training intensity was determined according to the predicted maximal heart rate. Demographic characteristics and medical history were collected via an interviewer-administered questionnaire at the baseline visit. Body fat was estimated based on skinfold thickness measured with calipers on the participant's nonsurgery side at the triceps, suprailiac crest. [Formula: see text] was estimated by 1-Mile Rockport Walk Test. Blood samples were collected 48 h before starting the exercise protocol and 48 h after the last exercise session. TNF-α, IL-6, IL-1ß, IL-10, and HSP70 levels in serum were measured using the enzyme-linked immunosorbent assay (ELISA) method according to the manufacture's instruction. Supernatant cytokine concentrations were determined by ELISA for IL-4 and IFN-γ. The data were analyzed by ANCOVA test that the pretest values were considered as covariate at P ≤ 0.05. RESULTS: HIIT improved [Formula: see text] in the HIIT group compared to the usual care group (P = 0.002). The serum levels of TNF-α (P = 0.001), IL-6 (P = 0.007), and IL-10 (P = 0.001) were lower in the HIIT group. The level of IL-4 (P = 0.050) in the stimulated peripheral blood mononuclear cells significantly increased in the HIIT group compared to the usual care group. Furthermore, the serum level of the HSP70 was significantly higher in the HIIT group in comparison to the usual care group (P = 0.050). The TNF-α/IL-10 (P = 0.050) and IL-6/IL-10 (P = 0.042) ratios were lower in the HIIT group. CONCLUSION: The results of this study indicated that HIIT has positive impacts on the cardiorespiratory fitness and inflammatory cytokines in the breast cancer patients undergoing hormone therapy.

Demographic Characteristics, Survival and Prognostic Factors of Early Breast Cancer Patients with Type 2 Diabetes Mellitus: A Hospital-Based Cohort Study

Objective: With increasing prevalence of type 2 diabetes mellitus and breast cancer in Iran, we aimed to search hospital registries of breast cancer patients to investigate type 2 diabetes mellitus association with survival outcomes of early breast cancer after adjustment of confounding factors. Methods: In a retrospective cohort study conducted from July 2003 to Feb 2014 and followed up until death or December 2016, female patients with early breast cancer who have been treated for the first time at the Cancer Institute of Iran, were divided to diabetic and non-diabetic groups. Primary and secondary outcomes were relapse free survival (RFS) and overall survival (OS). SPSS version 23 was used for analysis of data. Other variables included age, tumor stage, hormone receptor status, tumor subtype, and patient's body mass index (BMI). Result: From a total of 1021 patients, 218 (21.4%) had type 2 diabetes mellitus. Diabetic patients had a higher mean age (53.31 vs 47.00), higher mean BMI (31.13 vs 29.15), lower HER2 expression (20.8% vs 32.1%) and higher frequency of luminal A subtype (61.1% vs 51.0). Overall, after adjustment of other variables, diabetes status did not affect RFS or OS independently. However, in luminal A subgroup, patients with diabetes mellitus had significantly lower survival outcomes of OS (135.277 vs 154.701) and RFS (114.107 vs 133.612) as well as OS higher hazard ratio of 1.830 and RFS hazard ratio of 1.663 compared to non-diabetic patients. BMI, hormone receptor status and tumor stage significantly affected the survival of the patients. Conclusion: In the present study, in addition to known breast cancer risk factors, BMI and type 2 diabetes mellitus had an independent impact on survival of the patients, highlighting the importance of health issues such as obesity and diabetes suboptimal performance in the treatment outcomes of early breast cancer patients in Iran.

A Patient With Desmoid Tumors and Familial FAP Having Frame Shift Mutation of the APC Gene.

Desmoids tumors, characterized by monoclonal proliferation of myofibroblasts, could occur in 5-10% of patients with familial adenomatous polyposis (FAP) as an extra-colonic manifestation of the disease. FAP can develop when there is a germ-line mutation in the adenomatous polyposis coli gene. Although mild or attenuated FAP may follow mutations in 5΄ extreme of the gene, it is more likely that 3΄ extreme mutations haveamore severe manifestation of thedisease. A 28-year-old woman was admitted to the Cancer Institute of Iran with an abdominal painful mass. She had strong family history of FAP and underwent prophylactic total colectomy. Pre-operative CT scans revealed a large mass. Microscopic observation showed diffuse fibroblast cell infiltration of the adjacent tissue structures. Peripheral blood DNA extraction followed by adenomatous polyposis coli gene exon by exon sequencing was performed to investigate the mutation in adenomatous polyposis coli gene. Analysis of DNA sequencing demonstrated a mutation of 4 bpdeletions at codon 1309-1310 of the exon 16 of adenomatous polyposis coli gene sequence which was repeated in 3 members of the family. Some of them had desmoid tumor without classical FAP history. Even when there is no familial history of adenomatous polyposis, the adenomatous polyposis coli gene mutation should be investigated in cases of familial desmoids tumors for a suitable prevention. The 3΄ extreme of the adenomatous polyposis coli gene is still the best likely location in such families.

Estimation of the prevalence and direct medical costs of chronic myeloid leukemia in the I.R. of Iran in the era of tyrosine kinase inhibitors.

BACKGROUND: After the introduction of tyrosine kinase inhibitors for chronic myeloid leukemia (CML), the survival of these patients has increased significantly. However, these new drugs are expensive and impose considerable expense to patients and governments. Epidemiologic and economic evaluation studies provide good information for resource allocation and decision making. We estimated the incidence, prevalence and direct medical cost of CML in Iran. METHODS: We used the National Cancer Registry (NCR) data from 2006 to 2009 to estimate the incidence rate of CML (ICD-10 code C92.1). After adjustment for the underestimation of incidence rates, we used survival rates of CML and estimated the 5-year prevalence for these patients. In addition, we used clinical practice guideline, expert opinions and medical tariffs to estimate the direct medical costs through the prevalence approach. RESULTS: After an adjustment for the underestimation, the incidence rate of CML was 0.5 per 100 000 in the I.R. of Iran. The 5-year prevalence was about 2263 cases (2.98 per 100 000). The total direct medical cost of CML was $23 089 323 and the majority of the cost (97%) was related to drug costs. The total cost will increase considerably to $40 728 869 if all patients use the new drug nilotinib (800 mg/day) as a second-line treatment. CONCLUSIONS: The increased survival of CML patients and a possible increase in incidence of CML in Iran will most likely lead to a considerable rise in its prevalence and economic burden.

The effect of immunohistochemically detected p53 accumulation in prognosis of breast cancer; A retrospective survey of outcome.

BACKGROUND: P53; a tumor suppressor gene has known to have a role in a group of human cancers. Its role in breast cancer; one of the most prevalent malignancies worldwide, is still controversial. The current study is designed to evaluate the prognostic role of p53 mutation in breast cancer. METHODS: one hundred and eighty five breast cancer patients were studied in this retrospective study. P53 mutation was detected by accumulation of p53 protein in the patients' pathology samples. Immunohistochemistry (IHC) was used to detect the protein. The effect of p53 on the final outcome was assessed using Kaplan-Meier estimate of survival and compared by log-rank test. Prognostic effects analyzed by cox proportional hazard models. RESULTS: while the stage of the disease at presentation was not significantly different between p53 positive and negative patients, those with p53 mutation had a significantly poorer outcome in terms of overall and disease-free survival rates (OS and DFS). In a multivariate analysis hazard ratio of p53 mutation was about 5 and 3.8 for OS and DFS respectively. They also had a higher cumulative incidence of relapse. CONCLUSION: It seems that p53 mutation is an independent prognostic factor for breast cancer. Although larger prospective studies are needed to clarify the importance of such a conclusion.

Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF).

BACKGROUND: Health related quality of life (HRQOL) is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC) receiving either a standard or an experimental treatment. METHODS: Seventy-one patients have been treated in Cancer Institute (Tehran, Iran) with docetaxel, cisplatin, 5 FU (TCF) or epirubicin, cisplatin, 5-FU (ECF) and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy. RESULTS: The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001). Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups. CONCLUSION: Docetaxel based treatment (TCF) showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF). However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients.

Urine ratio of neutrophil gelatinase-associated lipocalin to creatinine as a marker for early detection of cisplatin-associated nephrotoxicity.

INTRODUCTION: Cisplatin is a widely used chemotherapeutic agent with a major side effect of nephrotoxicity. Delayed increase in serum creatinine after cisplatin injection makes serum creatinine not to be an ideal marker for early detection of cisplatin nephrotoxicity. Recently several new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) have been proposed for early detection of acute kidney injury (AKI). This study assessed kinetic of urine NGAL-creatinine ratio in patients who received cisplatin-containing chemotherapy. MATERIALS AND METHODS: Patients with a glomerular filtration rates greater than 45 mL/min who received cisplatin-containing chemotherapy were included. Urine creatinine and NGAL concentrations were measured before cisplatin infusion and 6, 24, 48, and 72 hours after cisplatin administration. To minimize hydration effects, urine NGAL levels were adjusted according to urine creatinine. RESULTS: Twenty-four patients were assessed. According to the Acute Kidney Injury Network criteria, 2 patients (8%) experienced cisplatin-associated AKI. The median increases in urine NGAL-creatinine ratio  were 335% (interquartile range, 320% to 350%) in the patients with AKI and 100% (interquartile range, 73% to 190%) in those without AKI (P = .02) during the first 24 hours after cisplatin administration. A urine NGAL-creatinine ratio greater than 26.9 ng/mg 24 hours after cisplatin infusion had a sensitivity of 86% and a specificity of 50% to detect cisplatin-associated nephrotoxicity. CONCLUSIONS: Urine NGAL-creatinine ratio significantly increased in patients with cisplatin-associated AKI. Urine NGAL-creatinine ratio within the first 24 hours after cisplatin infusion may better predict cisplatin-associated nephrotoxicity than serum creatinine level.