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.

Evaluation of the outcomes in patients with chronic myeloid leukemia treated with imatinib in 18-year follow-up.

The objective of this paper is to examine the effects of Imatinib on patients who are at the chronic phase of chronic myeloid leukemia (CML). Method: Totally, 79 patients with CML who received the treatment between 2003 and 2020 entered the study. The patients were evaluated in terms of molecular response rate and overall survival (OS). Results: About 75.9% of patients achieved deep molecular response in mean follow-up of 89.92 months. The OS rate was about 91.2%. Conclusion: There was no considerable cumulative toxicity with Imatinib long-term use. A high percent of patients had a deep molecular response.

Lesser Sac Glomangiosarcoma With Simultaneous Liver And Lymph Nodes Metastases Mimicking Small Bowel Gastrointestinal Stromal Tumor; Immunohistochemistry And Empirical Chemotherapy.

Glomangiosarcoma is a rare malignant mesenchymal tumor. Despite malignant histopathological feature of glomangiosarcoma, metastasis was observed extremely rare in these tumors. Moreover, malignant glomus tumor with stomach origination and simultaneous metastasis to liver and lymph nodes were not reported so far. This report presented a 57-year-old male patient with an exophytic gastric glomangiosarcoma in lesser sac and simultaneous liver and lymph node metastasis.

The recurrence frequency of breast cancer and its prognostic factors in Iranian patients.

BACKGROUND: Recurrent breast cancer (BC) after initial treatments is usually associated with poor outcome. The objective of this study is to evaluate baseline characteristics of BC patients to determine their prognostic influence of recurrences. MATERIALS AND METHODS: In this retrospective study of 481 BC patients, 182 patients who had recurrence within the first, second, or third 5 years after diagnosis were included in the study. The significant prognostic factors associated with late or very late recurrence were selected according to the Akaike Information Criterion. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. Also, very late recurrence was defined as initial recurrence after 10 years. RESULTS: During the follow-up period, 182 recurrences occurred (local recurrence or distant metastasis). All patients were treated with chemotherapy and radiotherapy and the patients with estrogen receptor (ER)- or progesterone receptor (PR)-positive had hormone therapy. There was a significant correlation between histological grade and receptors status with recurrence. In binary logistic regression analysis, ER and PR were significant prognostic factors for early recurrence. CONCLUSION: High histological grade and immunohistochemical markers (ER- and PR-negative or human epidermal growth factor receptor 2-positive) are risk factors for recurrence, especially in early recurrence and also between of them, ER is the more significant prognostic factor in early recurrence.

Retinal Toxicity of Intravitreal Granulocyte Colony-Stimulating Factor in Rabbit Eyes.

PURPOSE: Granulocyte colony-stimulating factor (G-CSF) has potential ocular neuroprotective effects. The aim of this study was to evaluate the retinal toxicity of intravitreal G-CSF in rabbit eye. METHODS: Eight New Zealand albino rabbits, weighing between 2 and 3 kg, were selected for this study. The initial concentration of G-CSF (300 µg/0.5 ml) was titrated to obtain different concentrations of 45 µg, 30 µg, 15 µg, and 7.5 µg in 0.1 ml. Each concentration was injected into two rabbit eyes. For each dose, dextrose was injected in one contralateral eye and the other fellow eye remained non-injected. Electroretinographic (ERG) testing was performed before and 4 weeks after injections. The rabbits were euthanized and the eyes were enucleated 4 weeks after injections and examined using light microscopy and immunohistochemistry. RESULTS: One rabbit with the injected dosage of 7.5 µg died at the first post-injection day. No sign of intraocular toxicity was found in clinical examination in other rabbits. A significant decrease in at least one of the a- or b-wave measurements of scotopic or photopic responses was found in 45 µg, 15 µg, and 7.5 µg injected eyes. Eyes with an intravitreal injection dosage of 30 µg G-CSF did not have significant changes compared to the baseline values. Histologic and immunohistochemistric studies were unremarkable for pathologic changes in all injected eyes. CONCLUSION: While histologic and immunohistochemistric examinations revealed no toxicity in all G-CSF-injected eyes, significant ERG changes were observed in all doses except for the dose of 30 µg/0.1 ml.

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status.

BACKGROUND: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. MATERIALS AND METHODS: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ≥10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. RESULTS: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also Ki-67≥20% as compared to the HER2-positive group. CONCLUSIONS: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ≥20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-67≥20% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

Effect of Oral Magnesium Oxide Supplementation on Cisplatin-Induced Hypomagnesemia in Cancer Patients: A Randomized Controlled Trial.

BACKGROUND: Hypomagnesaemia is one of the main side effects of cisplatin-based chemotherapy regimens in cancer patients. The aim of the current investigation was to evaluate the effect of oral magnesium oxide (MgO) supplementation on cisplatin-induced hypomagnesemia. METHODS: This parallel-randomized controlled, open label trial was conducted in a hospital of Iran University of Medical Sciences in Tehran between December 2009 and May 2011. Participants were 69 adult patients with newly diagnosed non- leukemia neoplasms candidate for starting cisplatin-based chemotherapy. Oral MgO supplement according to cisplatin dose (500 mg MgO per 50 mg/m(2) of cisplatin) as 2-3 divided daily doses was started after completion of each chemotherapy cycle and continued to the next cycle for the intervention group. Patients in the control group did not receive any supplementation. Serum magnesium (Mg) was measured before each chemotherapy cycle. The main outcome was measuring serum Mg change and hypomagnesaemia rate during chemotherapy treatment. RESULTS: Sixty-two participants (31 intervention- 31 controls) enrolled into the study. Serum Mg levels showed significant difference between the two groups (P=0.01). There was a significant decrease in serum Mg of the control group (P=0.001). At the end of follow-up period prevalence of hypomagnesaemia in the intervention group was 10.7% versus 23.1% in the control group. CONCLUSION: Continuously oral supplementation with MgO according to cisplatin dose (500 mg MgO per 50 mg/m(2) cisplatin) as 2-3 divided daily doses at rest days between chemotherapy cycles reduces the decline in serum Mg levels and also the prevalence of hypomagnesaemia in cancer patients.

Prevalence of Oxaliplatin-induced Chronic Neuropathy and Influencing Factors in Patients with Colorectal Cancer in Iran.

BACKGROUND: The chemotherapeutic agent oxaliplatin can cause acute and chronic forms of peripheral neuropathy. The aim of this study was to evaluate the incidence of chronic neuropathy and its risk factors in colorectal cancer (CRC) patients treated with FOLFOX or XELOX regimens in the Oncology Ward of Hazrat-e-Rasoul Hospital in Tehran. MATERIALS AND METHODS: A total of 130 patients with CRC were entered into our study, aged over 18 years, without history of receiving other neurotoxic agents or other predisposing factors such as diabetes or neurologic diseases and kidney and liver dysfunction. For the FOLFOX regimen, patients received oxaliplatin, 85 mg/m2, every 2 weeks for 12 courses and with the XELOX regimen, oxaliplatin was 130 mg/m(2), every 3 weeks for 8 courses. Based on Common Toxicity Criteria (CTC or NCI-CTC v.3), the patients were divided into 5 groups (grades) based on the severity of their symptoms. RESULTS: Fifty-seven patients (43.8%) were male and 73(56.2%) female. Some 19 patients (14.7%) had BMI<20, 97(74.6%) were between 20-25 and 14 (10.8%) ≥ 25. In 105 patients (80.7%) neuropathy was found. There was significant correlation between BMI, hypomagnesaemia and especially, severity of anemia in patients with neuropathy compared to those without. CONCLUSIONS: Oxaliplatin regimens can induce chronic neuropathy in CRC patients, with anemia, high BMI and hypomagnesaemia as risk factors that can predispose to this kind of neurotoxicity.

A 34 year old man with purple discoloration and paresthesia.

Secondary systemic vasculitis and nonbacterial endocarditis are rare events. We report a case presented with different manifestations of underlying malignancy such as systemic vasculitis, non bacterial endocarditis and DIC (disseminated intravascular coagulopathy). Efforts to find the source of malignancy was unsuccessful and due to patient's unwillingness for further evaluation, finally under the diagnosis of metastatic disease of unknown primary, patient is receiving cyclic chemotherapy.

Association between Anemia and COPD in Iranian Population.

BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) is one of the major causes of morbidity and mortality in adults. Anemia is known as comorbidity in many chronic diseases that can increase morbidity and mortality of COPD. Recent studies have shown that anemia may be more prevalent than expected in COPD patients and can increase disabilities of COPD. In this study we have evaluated the correlation between anemia and the severity of COPD in patients referred to teaching hospitals of the Tehran University of Medical Sciences (TUMS), Tehran, Iran. MATERIALS AND METHODS: In this cross-sectional study the severity of COPD in 760 patients with dyspnea who referred to teaching hospitals of Tehran University of Medical Sciences and 96 stable COPD patients were categorize using a GOLD criteria from mild to moderate, severe and very severe. Anemia was determined as hemoglobin <13 g/dL in men and <12 g/dL in women, respectively. Demographic characteristics, spirometry parameters and laboratory findings were compared between anemic and non-anemic groups using Student t-test and regression tests (SPSS v.18 software). RESULTS: The Mean age of patients was 65 ± 13.07 years (59.4% male). Overall prevalence of anemia was 27% and there was no correlation between severity of COPD and anemia. Anemic patients were significantly older than non-anemic patients (71.1 ± 8.5 years vs. 65.4± 12.8 years; p = 0.030). RBC count of anemic patients were significantly lower than non-anemic group (4.3 ± 0.5 vs. 5.02± 0.8 ×106/µL; p < 0.001). Erythropoietin levels in anemic group was significantly higher than non-anemic group (16.33±2.43 vs. 10.22 ± 2.67 mu/ml; p < 0.001) and there was a significant inverse correlation of hemoglobin vs erythropoietin (r= -0.8). CONCLUSION: There was a high prevalence of anemia in COPD patients. Anemia can increase disabilities of COPD. Thus, treatment of anemia may improve quality of life in these patients. Further comprehensive studies are needed for determination of exact prevalence of anemia and its physiologic effects in COPD.

Deep venous thrombosis and thrombophilic mutations in western Iran: association with factor V Leiden.

The aim of present study was to investigate the prevalence of factor V Leiden (FVL) c.1691G>A, prothrombin g.20210G>A and methylenetetrahydrofolate reductase (MTHFR) c.677C>T in deep vein thrombosis (DVT) patients and their possible association with DVT in western Iran. Eighty DVT patients with the mean age of 42.07 +/- 13.0 years including 44 women and 36 men and 100 sex-matched healthy individuals with the mean age of 37.63 +/- 13.3 years from Kermanshah Province of Iran with ethnic background of Kurd were studied for FVL c.1691G>A, prothrombin g.20210G>A and MTHFR c.677C>T by PCR-restriction fragment length polymorphism (RFLP) method using MnlI, HindIII and HinfI restriction enzymes, respectively. Prevalence of FVL was 11.4% in patients and 2% in control group. A significant association was found between FVL mutation and DVT with odds ratio (OR) of 6.3 [95% confidence interval (CI) = 1.32-30.05; P = 0.012]. The prevalence of prothrombin g.20210G>A variant in patients (3.8%) was nonsignificantly higher than control individuals (1.0%; OR 3.8; 95% CI = 0.39-37.81; P = 0.32). The prevalence of MTHFR c.677C>T in patients was 38.7% that was not statistically different from control group (44% P = 0.12). Venous thrombosis in legs was the most frequent clinical manifestation (n = 75), corresponding to 93.8% of the thromboembolism, followed by pulmonary thromboembolism (6.2%). We have, for the first time, determined the prevalence of inherited thrombophilia in a homogenous ethnic group of DVT patients and shown that FVL may be a risk factor for DVT in western Iran.