The Egyptian clinical trials’ registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov)

Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended

Gastric carcinoma at Tanta Cancer Center: A comparative retrospective clinico-pathological study of the elderly versus the non-elderly

Background and aims: To study the clinico-pathological features, treatments and outcomes of gastric carcinoma (GC) in the elderly (⩾65 years) and the non-elderly Egyptian patients. Methods: This retrospective cohort study included 168 patients with histologically confirmed GC treated at Tanta Cancer Center between 2003 and 2007. Results: Compared to the non-elderly, elderly patients had significantly higher proportion of tumors involving the cardia (p = 0.034) and of adenocarcinoma NOS histology (p = 0.032). Treatments were largely comparable in the two groups. Response to palliative chemotherapy was achieved in 44.4% of the elderly and 25.5% of the non-elderly patients (p = 0.417). The median overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 6, 17 and 3 months, respectively. The median OS was 4 months in the elderly compared to 9 months in the non-elderly (p = 0.005). The median DFS was 4 months in the elderly compared to 20 months in the non-elderly (p = 0.004). The median PFS was 2 months in the elderly compared to 3 months in the non-elderly (p = 0.685). In multivariate analysis, poor performance status was an independent predictor of poor OS, DFS and PFS. Non-curative or no surgery and lack of chemotherapy use were independent predictors of poor OS. Age was an independent predictor of poor DFS. Conclusions: Compared to the non-elderly, GC in the elderly has similar clinico-pathological characteristics and exhibits comparable outcomes with the same treatment options. Treatments should be tailored to each patient

Safety and efficacy of cetuximab-chemotherapy combination in Saudi patients with metastatic colorectal cancer

Background: Cetuximab-based combination chemotherapy (CBCC) proved safe and effective as second-line strategy for metastatic colorectal cancer (mCRC). This prospective phase-II study was designed to assess the efficacy and safety of CBCC as first-, second- or third-line among Saudi patients with mCRC. Materials and Methods: Patients with mCRC were offered CBCC to assess time-to-disease progression (TTP), response rate and duration, overall survival (OS) and safety. Results: Nineteen patients were eligible and their median age was 51 years. Seven patients received CBCC as first-line and 12 as second- or third-line. Responses: 11 (58%) partial responses, 5 (26%) stable disease and 3 (16%) disease progressions. The median response duration was 4.3 months [95% confidence interval (CI): 3.4-5.2 months]. The median TTP was 6.8 months (95% CI: 2-13.9 months) for all 19 patients compared to 9.3 months (95% CI: 3.9-14.6 months) for the seven patients who received CBCC as first-line. The median OS for the entire population was 12.3 months (95% CI could not be determined). On the other hand, while the median OS for those who received CBCC as first-line have not been reached, the median OS for those who received CBCC after failure of other salvage therapies was 12.3 months (95% CI: 3.2-21.4 months). CBCC was generally tolerable. One patient had a severe hypersensitivity reaction and another fatal cardiac arrest. Conclusion: CBCC is active with an acceptable safety profile. Until results from phase-III clinical trials are available, using CBCC as first-line is probably justified

First-line paclitaxel and cisplatin used sequentially or in combination in metastatic breast cancer: A phase II randomized study

Introduction: Breast cancer (BC) is the commonest cancer among females worldwide. Some patients present initially at advanced stages and more than 50% of them will develop metastasis (MBC) at some point. Compared to single agents, combination chemotherapy produces higher response rates (RR), longer progression-free survival (PFS) than single agents. This is associated with remarkably higher toxicities. At the same time, overall survival (OS) is comparable. This study aimed to compare safety and efficacy of combination and sequential chemotherapy. Patients and Methods: Forty-six MBC patients were randomized to receive 6 cycles of the combination of paclitaxel (175 mg/m2) and cisplatin (70 mg/m2) (combination PC) or paclitaxel for 3 cycles followed by cisplatin for 3 cycles (sequential PC). Endpoints were RR, PFS, OS and safety. Results: Both combination and sequential PC produced similar RR (52% in both arms) and disease control rates (78.3% vs. 73.9%, p = .652). Responses were faster in the combination arm. Median PFS was 8.2 months in the combination compared to 5.0 months in the sequential arm (p = .064). The median OS was 16.5 and 18.8 months in the combination and sequential arms, respectively (p = .866). The combination was more toxic than sequential PC. Grade 3 toxicities were higher with combination PC than to sequential PC (48% vs. 4.3%; p < .001). Conclusion: Sequential agent chemotherapy may provide similar response rate and overall survival to combination chemotherapy with much lower toxicities. The former can be considered the standard practice in most instances

Past, Present and Future of Colorectal Cancer in the Kingdom of Saudi Arabia

<b>Background/Aims:</b> The crude frequency of colorectal cancer (CRC) is second to breast cancer in the Kingdom of Saudi Arabia (KSA). To assess the future burden of CRC in the country, we designed a model that takes into consideration the recent lifestyle pattern and the growth and aging of the population. <b> Methods:</b> We compared CRC statistics for KSA (using data from the National Cancer Registry) with that from the Surveillance, Epidemiology and End Results (SEER) databases of the United States of America (USA). We used the Joinpoint regression program to identify changes in secular trends, while the GLOBOCAN 2002 software was used to project future incidence and mortality. <b> Results:</b> Between 1994 and 2003, age-standardized rates (ASRs) for CRC in KSA almost doubled, as compared to a nonsignificant decline in USA. Between 2001 and 2003, while the annual percent change (APC) of CRC incidence in the USA showed a nonsignificant decrease in females, APC in Saudi females showed a nonsignificant rise of six percent. On the other hand, the rising incidence among Saudi males, during the years 1999 to 2003, was significant, with an APC of 20.5&#x0025;. The projection model suggested that the incidence of CRC in KSA could increase fourfold in both genders by the year 2030. <b> Conclusions:</b> In KSA, the present and expected increase in CRC rates is alarming. Pragmatic recommendations to face that challenge are discussed. The present work could serve as a model to study other prevalent types of cancer, particularly in developing countries

Safety and efficacy of cetuximab-chemotherapy combination in Saudi patients with metastatic colorectal cancer

Background: Cetuximab-based combination chemotherapy (CBCC) proved safe and effective as second-line strategy for metastatic colorectal cancer (mCRC). This prospective phase-II study was designed to assess the efficacy and safety of CBCC as first-, second- or third-line among Saudi patients with mCRC. Materials and Methods: Patients with mCRC were offered CBCC to assess time-to-disease progression (TTP), response rate and duration, overall survival (OS) and safety. Results: Nineteen patients were eligible and their median age was 51 years. Seven patients received CBCC as first-line and 12 as second- or third-line. Responses: 11 (58%) partial responses, 5 (26%) stable disease and 3 (16%) disease progressions. The median response duration was 4.3 months [95% confidence interval (CI): 3.4-5.2 months]. The median TTP was 6.8 months (95% CI: 2-13.9 months) for all 19 patients compared to 9.3 months (95% CI: 3.9-14.6 months) for the seven patients who received CBCC as first-line. The median OS for the entire population was 12.3 months (95% CI could not be determined). On the other hand, while the median OS for those who received CBCC as first-line have not been reached, the median OS for those who received CBCC after failure of other salvage therapies was 12.3 months (95% CI: 3.2-21.4 months). CBCC was generally tolerable. One patient had a severe hypersensitivity reaction and another fatal cardiac arrest. Conclusion: CBCC is active with an acceptable safety profile. Until results from phase-III clinical trials are available, using CBCC as first-line is probably justified

Treatment outcomes of female germ cell tumors: The Egyptian National Cancer Institute experience

Introduction: Female germ cell tumors (GCTS) are rare tumors that carry a good prognosis. Aim: To report the experience of the Egyptian National Cancer Institute (ENCI) in managing female GCTs. Methods: This retrospective study included 19 females with ovarian GCTs presenting to the ENCI between 2006 and 2010. Results: The median age was 23 years. Ovaries were the primary site in all patients. Dysgerminoma and teratoma were the predominant pathologies followed by mixed GCT in females. Unilateral ovariectomy or ovarian tumorectomy were the classic surgical procedures with R0 resection being feasible in most cases. Surveillance was adopted in six patients with stage I disease. Chemotherapy was administered in 63% of ovarian GCTs with BEP being the commonest regimen with reasonable tolerability and good response rates. The median OS and EFS were not reached. The projected 5-year OS rate was 93.8%. Both OS and EFS were better in patients responding to chemotherapy than non-responders (p < 0.002). Stage of disease did not significantly affect OS or EFS. Conclusions: Female GCTs rarely affect Egyptian females. They have good prognosis

Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents—doxorubicin and cisplatin—is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients’ survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients’ response to TACE treatment in liver cancer

Protumorigenic role of Timeless in hepatocellular carcinoma.

The mammalian timeless (TIM) protein interacts with proteins of the endogenous clock and essentially contributes to the circadian rhythm. In addition, TIM is involved in maintenance of chromosome integrity, growth control and development. Thus, we hypothesized that TIM may exert a potential protumorigenic function in human hepatocarcinogenesis. TIM was overexpressed in a subset of human HCCs both at the mRNA and the protein level. siRNA-mediated knockdown of TIM reduced cell viability due to the induction of apoptosis and G2 arrest. The latter was mediated via CHEK2 phosphorylation. In addition, siRNA-treated cells showed a significantly reduced migratory capacity and reduced expression levels of various proteins. Mechanistically, TIM directly interacts with the eukaryotic elongation factor 1A2 (EEF1A2), which binds to actin filaments to promote tumor cell migration. siRNA-mediated knockdown of TIM reduced EEF1A2 protein levels thereby affecting ribosomal protein biosynthesis. Thus, overexpression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2