Significance of ERCC1 and Hormonal Receptor Expression in Ovarian Cancer.

Background & Objectives : Ovarian carcinoma usually has a relatively poor prognosis. A rational approach to identify patients, who are likely to benefit from therapy, is urgently needed. Excision repair cross-complementation group 1 enzyme (ERCC1) has been proposed as a molecular predictor of clinical resistance to platinum-based chemotherapy. Steroid hormone receptors are important determinants of prognosis and predictive behavior in tumor tissues of several origins. The present study aimed to investigate the expression profile of ERCC1, ER & AR in patients with Ovarian carcinoma and their association with patient outcome. Methods : This is a prospective study which included 77 patients with ovarian carcinoma who were treated with platinum based chemotherapy at the National Cancer Institute (NCI) in Egypt during the period 7/2016- 7/2018. We evaluated the expression of ER, AR, and Excision repair cross-complementation group 1 enzyme (ERCC1) by immunohistochemistry. Expression profiles were compared to clinical, histologic and prognostic factors, the clinical outcome and survival. All patients received platinum containing chemotherapy regimen. Result : Of the 77 patients with ovarian cancer, 66.2 % (51/77) were ERCC1-positive, 49.4 % (38/77) were AR positive & 75.3 % (58/77) were ER positive. Platinum resistance was found in eight of the tumors with positive ERCC1 protein expression compared with two among the patients with negative tumor staining for ERCC1 (P = 0.643). There was significant association between ER & AR expression and pathological subtypes (p = 0.004, 0.007) respectively. There were no significant association between ER, AR& ERCC1 expression and PFS (P = 0.447,P = 0.162, P = 0.508 respectively) or OS (P = 0.781, P = 0.569, P = 0.381 respectively). Based on Cox proportional hazards regression analysis ERCC1, ER &AR were not independent factors affecting the prognosis of patients with ovarian carcinoma. Conclusion : These results demonstrate that positive ERCC1 expression is not associated with clinical resistance to platinum-based chemotherapy, ERCC1, AR& ER expression are not independent factors affecting the prognosis of patients with epithelial ovarian tumors and not associated with survival benefits. J. Med. Invest. 67 : 391-398, August, 2020.

Diagnosis and predictive molecular analysis of non-small-cell lung cancer in the Africa-Middle East region: challenges and strategies for improvement.

The identification of tumor biomarkers provides information on the prognosis and guides the implementation of appropriate treatment in patients with many different cancer types. In non-small cell lung cancer (NSCLC), targeted treatment plans based on biomarker identification have already been used in the clinic. However, such predictive molecular testing is not currently a universally used practice. This is the case, in particular, in developing countries where lung cancer is increasingly prevalent. In September 2012 and November 2013, a committee of 16 lung cancer experts from Africa and the Middle East met to discuss key issues related to diagnosis and biomarker testing in NSCLC and the implementation of personalized medicine in the region. The committee identified current challenges for effective diagnosis and predictive analysis in Africa and the Middle East. Moreover, strategies to encourage the implementation of biomarker testing were discussed. A practical approach for the effective diagnosis and predictive molecular testing of NSCLC in these regions was derived. We present the key issues and recommendations arising from the meetings.

Modification and implementation of NCCN guidelines on prostate cancer in the Middle East and North Africa region.

A prostate cancer committee was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Prostate Cancer for adaptation and implementation in the Middle East and North Africa (MENA) region. The objective was to enhance the multidisciplinary approach to the treatment of prostate cancer. The committee, comprising regional experts in the fields of urologic, medical, and radiation oncology, reviewed the 2009 version of the NCCN Guidelines on Prostate Cancer and suggested modifications based on the unique needs of the regions determined through published evidence and local expertise. The committee identified several areas in the NCCN Guidelines that they believed required modification, which are presented in this article. The treatment of prostate cancer in the MENA region has numerous challenges. The hope is that this effort to modify the NCCN Guidelines on Prostate Cancer for practical use in the MENA region will improve regional awareness and patient care.

Gemcitabine plus doxorubicin as first-line treatment in advanced or metastatic breast cancer (MBC), a phase II study.

INTRODUCTION: Doxorubicin and Gemcitabine have promising antineoplastic activity and manageable toxicity as a single agent in the treatment of patients (pts) with advanced breast cancer. AIM OF THE STUDY: This study evaluated the efficacy and toxicity of the combination of gemcitabine plus doxorubicin as first-line treatment of advanced or MBC patients. PATIENTS AND METHODS: Patients with advanced or MBC received gemcitabine 1250mg/m2 IV on days 1 and 8 plus doxorubicin 60mg/m2 IV on day 1 every 21 days for a maximum of 6 cycles. RESULTS: Thirty-five patients were included, and all are evaluable for safety and efficacy. Median age was 47 years (range, 33 to 60 years). Fourteen patients (40%) were post-and 21 (60%) were premenopausal. Prior treatment included mastectomy (23pts); adjuvant nonanthracycline containing combination chemotherapy (18pts); adjuvant hormonal therapy (3pts) and 2 pts did not receive any adjuvant therapy. Twelve patients had metastatic disease at presentation. Seventeen pts were chemonaive. Hormonal receptors were positive in 6, negative in 21, and unknown in 8 pts. Site of metastasis included one site in 15 pts, two sites in 14, and three sites in 6 pts. Complete remission was observed in 6/35 (17.1%) and partial remission in 14/35 (40%) pts, for an overall response rate of 57.1%. Stable disease was observed in 8 (22.9%) and progressive disease in 7 (20%) pts. The median time to tumor progression was 7 months (range, 5-23 months; 95% CI, 6-8 months) and the median survival time was 16 months (range, 6-43 months; 95% CI, 13-19 months). The overall survival at 1 and 2 years was 74.2% and 34.2%; respectively; with 4/35 (11.4%) patients alive at 40 months. A total of 186 cycles of treatment were administered (range2-6 cycles, median 6 cycles). The doses of both doxorubicin and gemcitabine were modified after interim analysis of toxicity following the first 22 cycles administered to the first 10 patients [Mucositis grade 3-4 occurred in 6/10 (60%), grade 3-4 neutropenia in 3/10 (30%), and febrile neutropenia grade 3 in 2/10 (20%) patients] to doxorubicin 50mg/m2 on day 1 and gemcitabine to 1000 mg/m2 on days 1 and 8 in the remaining cycles. After doses reduction, the toxicity was generally tolerable. CONCLUSION: The combination of gemcitabine plus doxorubicin after doses modification can be safely administered every 21 days with promising response as first-line therapy for MBC. The response rate, time to disease progression and overall survival rates of this regimen are comparable to other standard therapies for MBC, as well as other gemcitabine combinations.