Clinical recommendations in the management of advanced prostate cancer: International Gastrointestinal, Liver and Uro-oncology (IGILUC 2019) experts.

PURPOSE: Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas. METHODS: Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand. RESULTS: A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps. CONCLUSION: This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer.

BACKGROUND: Maintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research. METHODS: This multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500 mg/m2 every 21 days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4 cycles of induction chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs). RESULTS: A total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n = 28) or BSC (n = 27). Although the median PFS time for maintenance phase for both arms was 3.2 months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR = 0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value = 0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2 months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8 months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the induction and continuation maintenance therapies were generally well-tolerated, and similar proportion of patients in each arm experienced at least 1 grade 3/4 TEAE (pemetrexed/BSC, 17.9%; BSC, 18.5%). CONCLUSIONS: Continuation pemetrexed maintenance therapy resulted in promising PFS with an acceptable safety profile in a Middle Eastern population with advanced non-squamous NSCLC and is worthy of further investigation. TRIAL REGISTRATION: NCT00606021.

Type I insulin-like growth factor as a liver reserve assessment tool in hepatocellular carcinoma.

Chronic liver diseases (CLDs) encompass a wide range of illnesses, including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and viral hepatitis. Deterioration of liver capacity, with subsequent progression into cirrhosis and hepatocellular carcinoma (HCC), ultimately leads to a further decrease in the hepatic reserve. The Child-Turcotte-Pugh scoring system is the standard tool for assessing underlying liver reserve capacity in routine practice and in clinical trials of CLD and HCC. In this review, we highlight the clinical significance of insulin-like growth factor-I (IGF-I) and the growth hormone (GH) signaling pathway in HCC. IGF-I could be a marker for liver reserve capacity in CLDs and HCC in clinical practice. This approach could improve the risk assessment and stratifications of patients on the basis of their underlying liver reserve, either before active treatment in routine practice or before they are enrolled in clinical trials.

Validation of an IGF-CTP scoring system for assessing hepatic reserve in Egyptian patients with hepatocellular carcinoma.

BACKGROUND: The Child-Turcotte-Pugh score (CTP) is the standard tool for hepatic reserve assessment in hepatocellular carcinoma (HCC). Recently, we reported that integrating plasma insulin-like growth factor-1 (IGF-1) level into the CTP score was associated with better patient risk stratification in two U.S. independent cohorts. Our current study aimed to validate the IGF-CTP score in patients who have different demographics and risk factors. PATIENTS AND METHODS: We prospectively recruited 100 Egyptian patients and calculated their IGF-CTP score compared to CTP score. C-index was used to compare the prognostic significance of the two scoring systems. Finally, we compared our results with our U.S. cohorts published data. RESULTS: IGF-CTP score showed significant better patient stratification compared to CTP score in the international validation cohort. Among CTP class A patients, who usually considered for active treatment and clinical trial enrollment, 32.5% were reclassified as IGF-CTP class B with significantly shorter OS than patients reclassified as class A with hazard ratio [HR] = 6.15, 95% confidence interval [CI] = 2.18 -17.37. CONCLUSIONS: IGF-CTP score showed significantly better patient stratification and survival prediction not only in the U.S. population but also in international validation population, who had different demographics and HCC risk factors.

A phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer.

BACKGROUND AND OBJECTIVES: There is an unmet need for new combination treatments, especially for aggressive, visceral, and high tumor burden metastatic breast cancer. Gemcitabine (GEM) has shown synergy with vinorelbine (VRL) in preclinical models, and has a toxicity profile that is different from VRL, another recently approved cytotoxic drug that seems to be effective in the treatment of breast cancer. METHODS: We studied the efficacy and side effects of the GEM-VRL combination as first-line chemotherapy in patients in an open-label, single arm, phase II study in patients with locally advanced or metastatic breast cancer who had been previously treated with an anthracycline-based regimen in the adjuvant/neoadjuvant setting. RESULTS: Of the 74 patients enrolled, 72 patients were evaluable for the primary treatment outcome (tumor response rates). Four patients (6%) had a complete response and 26 patients (36%) had a partial response. Nineteen patients (26%) had stable disease. The median time to disease progression was 37 weeks (range, 1-60 weeks). Median duration of response was 43 weeks (range, 8.6 to 55 weeks) and one-year survival was 77% (95% confidence interval, 64% to 86%). Grade 3-4 neutropenia without fever was reported in 10% of patients, thrombocytopenia in 1%, and febrile neutropenia in 11%. The most common clinical grade 3-4 toxicities were nausea (24%) and diarrhea and stomatitis (11% each). Hospitalizations for adverse events mainly due to anemia, febrile neutropenia, septic shock and hepatic failure occurred in 7%. CONCLUSION: With an overall response rate of 42%, the GEM-VRL combination had promising efficacy and good tolerability in metastatic breast cancer patients.