Multimodal Treatment Strategies in Esophagogastric Junction Cancer: a Western Perspective

Esophagogastric junction (EGJ) cancer is a solid tumor entity with rapidly increasing incidence in the Western countries. Given the high proportion of advanced cancers in the West, treatment strategies routinely employed include surgery and chemotherapy perioperatively, and chemoradiation in neoadjuvant settings. Neoadjuvant chemoradiation and perioperative chemotherapy are mostly performed in esophageal cancer that extends to the EGJ and gastric as well as EGJ cancers, respectively. Recent trials have tried to combine both strategies in a perioperative context, which might have beneficial outcomes, especially in patients with EGJ cancer. However, it is difficult to recruit patients for trials, exclusively for EGJ cancers; therefore, the results have to be carefully reviewed before establishing a standard protocol. Trastuzumab was the first drug for targeted therapy that was positively evaluated for this tumor entity, and there are several ongoing trials investigating more targeted drugs in order to customize effective therapies based on tissue characteristics. The current study reviews the multimodal treatment concept for EGJ cancers in the West and summarizes the latest reports.

Prognostic Factor Analysis of Overall Survival in Gastric Cancer from Two Phase III Studies of Second-line Ramucirumab (REGARD and RAINBOW) Using Pooled Patient Data

PURPOSE: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. MATERIALS AND METHODS: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. RESULTS: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. CONCLUSIONS: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

Impact of age on the feasibility and efficacy of neoadjuvant chemotherapy in patients with locally advanced oesophagogastric cancer.

INTRODUCTION: Neoadjuvant chemotherapy (neoCTx) improves the prognosis of patients with localised oesophagogastric adenocarcinoma (EGC), but its value is unknown in elderly patients. PATIENTS AND METHODS: Patients who received neoCTx followed by surgery for EGC between 2000 and 2012 were analysed. The aim of this study was to compare the feasibility and outcome between patients aged ⩾70 (cohort I) and their younger counterparts (cohort II). RESULTS: Data were available for 460 patients among which 174 (38%) were ⩾70 years. Older age was associated with an increased rate of comorbidities (66% versus 42%, p<0,001). As compared to the younger, elderly patients were more likely to receive doublet instead of triplet neoCTx (65% versus 37%, p<0.001) and oxaliplatin-instead of cisplatin-based regimens (60% versus 32%, p<0.001). No significant difference was observed in the rate of ⩾grade 3 toxicities for cohort I and II (48% versus 41%) and postoperative morbidity was also not different (24% versus 28%). 90 day mortality for cohort I and II was 6.5% and 3.9%. After a median follow-up of 38 months, median disease-free survival (DFS) was 29.4 months in cohort I and 33.8 months in cohort II, with a 5-years DFS of 37% and 40%, respectively. Median overall survival (OS) was not reached in cohort I and was 58.4 months in cohort II, with a 5-year OS of 51% and 50% for cohort I and II, respectively. DISCUSSION: Despite slightly more adverse events and dose reductions, neoCTx is feasible in elderly patients with EGC. Elderly patients achieve comparable survival outcomes compared with their younger counterparts.

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice.

BACKGROUND: The combination of nab-paclitaxel and gemcitabine is a new effective first-line chemotherapy for patients with metastatic pancreatic cancer. This was demonstrated in the phase III MPACT trial. PATIENTS AND METHODS: Four patients with metastatic pancreatic cancer from our clinical practice received combination chemotherapy with nab-paclitaxel at doses from 100 to 125 mg/m(2) and gemcitabine at doses from 800 to 1,000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Two patients had elevated serum levels of total bilirubin, one older patient had significant comorbidities, another older patient had an Eastern Cooperative Oncology Group performance status of 2. RESULTS: Treatment was manageable. Patients showed clinical remission or disease stabilization. Overall, combination chemotherapy was well tolerated. CONCLUSION: Patients with metastatic pancreatic cancer that did not meet all criteria, as patients treated in the registration trial, were safely and effectively treated with first-line combination of nab-paclitaxel and gemcitabine.