Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020.

PURPOSE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. METHODS: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. RESULTS: The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. CONCLUSION: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

Personalized treatment is better than one treatment fits all in the management of patients with mCRC: a consensus statement.

The VEGF- (bevacizumab) and EGFR- (cetuximab and panitumumab) targeting monoclonal antibodies have become integral components of the first-line treatment strategies for patients with metastatic colorectal cancer (mCRC). Increasingly combination chemotherapy, with or without a targeted agent, is being used to facilitate curative liver resection and improve survival rates in patients with initially unresectable but potentially resectable mCRC. Currently, the only selective marker for the treatment of patients with mCRC is tumor RAS mutational status. BRAF status is a strong prognostic indicator. Medical and clinical oncologists from Central Asia, Russia, the Middle East, Africa and Turkey reviewed data for the use of targeted agents in the treatment of patients with mCRC and have formed recommendations for the biological of choice first-line for patients with mCRC.

Adjuvant chemotherapy for luminal A breast cancer: a prospective study comparing two popular chemotherapy regimens.

INTRODUCTION: Based on the variable benefit of taxanes in the adjuvant setting of early breast cancer in certain tumor phenotypes, especially in human epidermal growth factor receptor (HER)2-positive and triple-negative disease, and with the observation of a lesser benefit in luminal A, this research article aimed at exploring the value of docetaxel in patients with an estrogen receptor-positive, HER2-negative disease phenotype, who might not derive the same benefits as those with other phenotypes. PATIENTS AND METHODS: This was a randomized prospective study comparing disease-free survival (DFS) and safety profile of sequential adjuvant three cycles Fluorouracil, Epirubicin, Cyclophosphamide followed by three cycles Docetaxel (FEC-D) versus six cycles classic Fluorouracil, Epirubicin, Cyclophosphamide (FEC)-100 in 60 Egyptian women who presented to Dar Al Fouad Hospital during the period June 2007 to July 2008 with (pT1-2 pN0-3 M0). The primary end point was DFS in a follow-up period of 4 years. The secondary end point was toxicity profile. RESULTS: Four-year DFS rates were comparable in both arms: 73.3% ± 8.1% in the FEC-D arm versus 76.5% ± 7.8% in the FEC-100 arm (P = 0.83). N3 and grade III subgroups achieved the worst DFS in both subgroups (P = 0.001 and P = 0.214, respectively). The rate of nausea and vomiting was higher in the FEC-100 arm (P = 0.49), while grade III-IV neutropenia and febrile neutropenia incidence was similar between both arms. CONCLUSION: Sequential adjuvant chemotherapy with FEC followed by docetaxel achieved comparable DFS results to FEC alone in luminal A phenotype subgroups of breast cancer.

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation.

PURPOSE: The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients. PATIENTS AND METHODS: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR) mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m(2) on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m(2) on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. RESULTS: The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III-IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06), DVT (P = 0.23), proteinuria (P = 0.23), and hypertension (P = 0.11), as well as Grade II alopecia (P = 0.001); however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66), hematological toxicity, febrile neutropenia (P = 1) and fatigue (P = 0.66). Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978). Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89). CONCLUSION: Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy in advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. No significant difference in toxicity was observed between both treatment arms, apart from bevacizumab/carboplatin/paclitaxel-related risks as DVT, hypertension, proteinuria, sensory/motor neuropathy, and alopecia.

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel versus carboplatin/docetaxel in initial treatment of metastatic Her-2-negative breast cancer.

PURPOSE: In view of the previous reports demonstrating the positive outcome of bevacizumab in metastatic breast cancer, we aimed at comparing the role of bevacizumab-based metronomic combination with taxane (paclitaxel) versus a different taxane (docetaxel)-based regimen in addition to carboplatin as initial treatment for metastatic Her-2-negative breast cancer. PATIENTS AND METHODS: This is a randomized Phase III study comparing the progression-free survival (PFS) and safety in Her-2-negative female patients with initial diagnosis of metastatic breast cancer with World Health Organization performance status of 0-II. Forty-one patients were randomized from September 2008 to July 2009 to receive either; (1) bevacizumab 5 mg/kg day 1 and day 15, carboplatin area under the curve (AUC)-2 day 1, day 8, and day 15, and paclitaxel 60 mg/m(2) day 1, day 8, and day 15 (arm-I); or (2) carboplatin AUC-5 day 1, docetaxel 75 mg/m(2) day 1 (arm-II). The Kaplan-Meier method was used for estimating survival; log-rank test for comparing survival curves. The primary end point was PFS, and secondary end points were overall survival (OS) and safety. RESULTS: PFS was 10 months in arm I versus 10.2 months in arm II (P = 0.9). The OS rate was similar in both arms: 37.6 months for arm I versus 37.4 months for arm II (P = 0.92). The toxicity revealed higher incidence of hypertension and proteinuria in arm I; however, with higher incidence of grade III-IV neutropenia and neutropenic fever in arm II. No treatment-related mortality was recorded. CONCLUSION: Bevacizumab/carboplatin/paclitaxel and carboplatin/docetaxel show comparable PFS and OS with different toxicity profiles.

A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer.

BACKGROUND: Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder cancer. PATIENTS AND METHODS: Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months. RESULTS: The patients (n = 40) were evenly distributed between the two treatment groups, and the baseline demographics of the two groups were similar. The follow-up varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 +/- 1.0 vs. 0.95 +/- 0.9, respectively), and a larger proportion did not experience an on-study SRE (2 vs. 8 patients, respectively). Zoledronic acid also prolonged the median time to first SRE compared with the placebo (16 vs. 8 weeks, respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared with placebo (36.3 +/- 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient population. CONCLUSIONS: Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of patients with bone metastases from bladder cancer, potentially through its anticancer activity.