Fadi El Karak

Immune checkpoint inhibitors renal side effects and management

The next decade in cancer therapy will be marked by the expansion of immunotherapies, namely immune checkpoint inhibitors. The increasing number and combination of checkpoint inhibitors and the variety of their mechanisms of action and indications will most likely multiply the side effects associated with these therapies and make their management more complicated and diversified. Given the growing rate of approval of different checkpoint inhibitors in different cancers in multiple settings, a review summarizing the major side effects of the new agents in use today and their management seems to be appropriate. Highlighting these adverse events and their management in a single review might help the daily practice of the physicians and consequently contribute the patients safety and quality of life.

Optimum chemotherapy in the management of metastatic pancreatic cancer

Pancreatic cancer is one of the most devastating solid tumors, and it remains one of the most difficult to treat. The treatment of metastatic pancreatic cancer (MPC) is systemic, based on chemotherapy or best supportive care, depending on the performance status of the patient. Two chemotherapeutical regimens have produced substantial benefits in the treatment of MPC: gemcitabine in 1997; and FOLFIRIONOX in 2011. FOLFIRINOX improved the natural history of MPC, with overall survival (OS) of 11.1 mo. Nab-paclitaxel associated with gemcitabine is a newly approved regimen for MPC, with a median OS of 8.6 mo. Despite multiple trials, this targeted therapy was not efficient in the treatment of MPC. Many new molecules targeting the proliferation and survival pathways, immune response, oncofetal signaling and the epigenetic changes are currently undergoing phase I and II trials for the treatment of MPC, with many promising results.

Triple-Negative Breast Cancer in Lebanon: A Case Series

OBJECTIVES To determine the incidence, characteristics, and survival outcomes of triple-negative breast cancer patients in a medical oncology practice in Lebanon. METHODS The pathology reports of all breast cancer cases diagnosed or treated in 1997-2008 were reviewed. RESULTS One hundred seventy breast cancer cases (9.3%) of the 1,834 cases that were identified in this practice over a 10-year span had a triple-negative phenotype, with a median age at diagnosis of 52 years. The pathology distribution of those cases was as follows: invasive ductal carcinoma, 85%; medullary carcinoma, 5%; invasive lobular carcinoma, 5%; 95 cases (63%) were grade III. At diagnosis, 17% presented with stage I, 47% had stage II, 24% had stage III, and 12% had stage IV disease, whereas 11% had an inflammatory component. After a median follow-up of 17 months, 43 patients (25.3%) had relapsed and the most common sites of relapse were the brain (19%), lungs (19%), and bones (12%). The risk for recurrence peaked at 1.5 years and became almost nil after 3 years. Twenty patients received induction chemotherapy, among whom six (42.9%) had a complete response and six (42.9%) had a partial response to treatment. None of the patients progressed on neoadjuvant chemotherapy. The 5-year disease-free survival rate was 75% for stage I, 58% for stage II, and 40% for stage III patients, whereas the 5-year overall survival rate was 88% for stage I, 72% for stage II, and 63% for stage III patients. Adjuvant therapy was administered to 96% of patients, using a taxane-based regimen in 38% of cases. The median survival time for stage IV patients was 19 months, with a first line taxane-based regimen used in 50% of cases. CONCLUSIONS The incidence of triple-negative breast cancer in Lebanon is similar to that described in the literature. In order to determine targets for future therapeutic options, it is essential to understand the biology of this particular breast cancer subtype.

Optimum chemotherapy for the management of advanced biliary tract cancer.

Biliary tract cancers (BTCs) are highly fatal malignancies, which are often diagnosed at an advanced stage and have relatively poor prognosis. The treatment of patients with advanced BTC is systemic, based on chemotherapy or best supportive care, depending on their performance status. Despite clinical trials studying many chemotherapeutic regimens and targeted therapies for the treatment of BTC, the standard of care for advanced BTC remains the combination of gemcitabine with cisplatin. Many new molecules targeting proliferation and survival pathways, the immune response and angiogenesis are currently undergoing phase I and II trials for the treatment of advanced BTC with promising results.

PET/CT Scanner and Bone Marrow Biopsy in Detection of Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma

Evaluation of bone marrow involvement (BMI) is paramount in diffuse large B-cell lymphoma (DLBCL) for prognostic and therapeutic reasons. PET/CT scanner (PET) is now a routine examination for the staging of DLBCL with prognostic and therapeutic implications. This study evaluates the role of PET for detecting marrow involvement compared to bone marrow biopsy (BMB). This monocentric study included 54 patients diagnosed with DLBCL between 2009 and 2013 and who had FDG PET/CT in a pre-treatment setting. A correlation analysis of the detection of BMI by PET and BMB was performed. A prognostic evaluation of BMI by BMB and/or PET/CT and correlation with an overall 2-year survival were analyzed. PET was more sensitive for the detection of BMI than BMB (92.3% vs. 38.5%). It can be considered a discriminatory Pre-BMB test with a negative predictive value of 97.6%. In addition, BMI by PET had a prognostic value with strong correlation with progression-free survival (PFS) (HR = 3.81; p = 0.013) and overall survival (OS) (HR = 4.12; p = 0.03) while the BMB had not. PET shows superior performance to the BMB for the detection of marrow involvement in DLBCL. It may be considered as the first line examination of bone marrow instead of the biopsy.

Review and results of a survey about biosimilars prescription and challenges in the Middle East and North Africa region

BackgroundOnly drafts of regulatory guidelines for the registration of biosimilars are available in Lebanon. We analyzed the results of a regional survey conducted in Lebanon to understand the impact of different parameters on the acceptance and future prescription of biosimilars. We also reviewed the current situation of biosimilars around the world. The study surveyed healthcare professionals from the Arab countries, Iran, Belgium and Italy. Data about the participants’ specialty, country of residence, their knowledge about biosimilars, biosimilars’ prescription, price influence and the manufacturer’s credibility were collected.Results117 questionnaires were completed and returned: 46 (39.3%) respondents were oncologists. 72 (61.5%) respondents were Lebanese, and the others from Egypt, Syria, Algeria, Iraq, Sudan, Jordan, Iran, Belgium and Italy. 77 (65.8%) respondents had knowledge about biosimilars, of whom 48 (62.3%) considered biosimilars as biologics that demonstrate bioequivalence with the original biodrug and have all preclinical and clinical trials equal to those already performed with the original biodrug. 74 (63.2%) out of 117 respondents agreed that biosimilars in the Arab and Middle Eastern market are already marketed. Among the 48 participants who prescribe biosimilars, the main prescription driver was the drug’s approval by the FDA and EMA (68.8%). 71 (60.7%) respondents considered that the main advantage of biosimilars is their lower price and 41 (35%) out of the 117 respondents declared that they should know in which country the drug has been tested/created before using it in their own country. 35% of the respondents thought that the cost of a treatment should not come before its effectiveness or safety/tolerance, given that the biosimilar will be less expensive than the reference drug.ConclusionsBiosimilars’ acceptance and use is increasing worldwide. Only few physicians are aware of biosimilars presence in the market and do prescribe them in Lebanon and the Arab region. This could be mainly explained by lack of confidence in efficacy, safety, manufacturing process and price of these products, and lack of clear legislation. Thus, WHO is finalizing a new guideline for similar biotherapeutic agents. This could be a starting point for the Lebanese government to support the authorization of biosimilars.

The Therapeutic use of human albumin in cancer patients’ management

Human albumin (HA) has been widely used in clinical practice due to its unique physiological characteristics and pharmacokinetics. However, with the absence of clear institutional recommendations, its uncontrolled prescription remains largely controversial. An extensive review on the albumin chemistry, pharmacology, physiology and pathology was performed, and data on commercially available HA, its cost, medical usage and the related available guidelines, particularly in oncology patients were gathered. Studies assessing the appropriate use and safety of HA in cancer patients are lacking. A retrospective survey of the appropriateness of HA infusions according to the SIMTI guidelines (2009) was performed in our department. Among 53 patients who received HA infusions, only 5.7% of the indications were appropriate for HA administration. Occasionally appropriate and inappropriate indications were considered in 10% and 84.3% of the prescriptions respectively with a relatively high cost. The adoption of strict guidelines may substantially reduce the inappropriate use and the subsequent healthcare costs.

Could the combination of Nab-paclitaxel plus gemcitabine salvage metastatic pancreatic adenocarcinoma after folfirinox failure? A single institutional retrospective analysis

Sex Male 10 (83.3%) Female 2 (16.7%) Age (years), median (range) 61 (52—74) Comorbidities, median (range) 1.5 (1—4) Smoking 8 (66.7%) Diabetes mellitus 6 (50%) High blood pressure 5 (41.7%) Hyperlipidemia 2 (16.7%) Pancreatic tumor location Head 8 (66.7%) Body 3 (25%) Tail 1 (8.3%) Metastatic sites, median (range) 1.5 (1—3) Liver — (exclusive) 11 (91.7%) — 5 (41.7%) Peritoneum 2 (16.7%) Adrenal gland 1 (8.3%) First-line chemotherapy Folfirinox 12 (100%) Number of cycles, median (range) 9 (2—36)

Where does chemotherapy stands in the treatment of ampullary carcinoma? A review of literature

Ampullary carcinoma (AC) is a rare gastrointestinal tumor without clear treatment recommendations. The management of this tumor is usually extrapolated from the treatment of pancreatic, biliary duct and intestinal cancers. Few papers have studied the AC as an independent entity and yet succombs to several limitations. These studies were retrospective single institutional experiences with limited sample sizes recruited over a long period of time. Unlike metastatic ACs where chemotherapy is the only recommended option, localized AC once excised may be approached by either chemotherapy alone or concomitant chemoradiation therapy. In this review, we report the overall survival and recurrence factors of more than 1000 patients from all the studies treating exclusively ACs. We also review the medical treatment of this tumor and conclude to the necessity of multi-institutional randomized controlled studies for AC exclusively.

Efficacy and safety of everolimus in hormone receptor positive breast cancer in a developing country: Real-life single institutional experience

Introduction: Breast cancer is the second leading cause of cancer-related mortality despite the staggering improvement in cancer therapeutics. So far, published data illustrate endocrine therapy as the cornerstone treatment for patients with hormone receptor-positive metastatic breast cancer. Unfortunately, most patients eventually develop resistance to this treatment. Methods: The purpose of this study is to evaluate the efficacy of mammalian target of rapamycin inhibition in reversing hormone resistance in the Lebanese breast cancer patients. Efficacy of the intervention according to the independent factors and notable side effects encountered were the primary points of the evaluation. Results: In total, fifty patients received the combination of everolimus and exemestane. The mean age of the study population was 61 ± 11 years. Sensitivity to hormonal therapy before the start of the combination treatment was estimated at 64%. Response rate was 14%, and all patients were partial responders. After regular interval evaluation, the median progression-free survival was 5.2 months since the initiation of therapy. The main toxicities associated with the combination were stomatitis (22%), myalgia (22%), skin toxicity (8%), and hyperglycemia (4%), all Grades 1 and 2. Conclusion: Everolimus has been shown to be effective in overcoming hormonal resistance in Lebanese breast cancer patients with results inferior to those reported in the BOLERO-2 population. The particular differences in molecular and pathological aspects of breast cancer in our region should stimulate the extensive research for a better understanding of the particular pattern of the disease.