Prognostic role of sodium levels in colorectal cancer patients receiving aflibercept plus FOLFIRI.

Aim: To investigate the impact of natremia in metastatic colorectal cancer (mCRC) patients treated with aflibercept plus folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRI). Patients & methods: A total of 84 mCRC patients receiving aflibercept plus FOLFIRI as second-line treatment were enrolled and divided into two groups based on their median sodium value. Progression-free survival and overall survival were analyzed. Results: Patients with sodium levels ≥140 mEq/l had significantly longer median progression-free survival (4.1 vs 2 months; p < 0.01) and median overall survival (12 vs 7.3 months; p < 0.01) compared with those with lower levels. Conclusion: This study suggests that higher pretreatment serum sodium levels are associated with improved outcomes in mCRC patients receiving aflibercept and FOLFIRI, potentially serving as a prognostic marker to aid treatment management.

What is this article about? Colorectal cancer (CRC) is a common and deadly disease. Despite advances in treatment options, the prognosis remains poor for patients who progress beyond the first-line therapy. Antiangiogenic therapy, which targets blood vessel growth in tumors, has become an important treatment approach for metastatic CRC (mCRC). Aflibercept is a drug used in combination with chemotherapy to treat mCRC patients who have progressed after initial treatment. However, there is limited knowledge about factors that can predict the effectiveness of this treatment. This study aimed to investigate the relationship between sodium levels and treatment outcomes in 84 mCRC patients receiving aflibercept and chemotherapy as second-line therapy. What were the results? The results showed that patients with baseline sodium levels of ≥140 mEq/l had significantly longer progression-free survival and overall survival compared with patients with lower sodium levels. This finding suggests that baseline serum sodium levels could serve as a prognostic factor for survival outcomes in mCRC patients treated with aflibercept and chemotherapy. Other factors associated with better survival outcomes included longer survival without disease progression after first-line chemotherapy, receiving maintenance treatment with aflibercept and completing more treatment cycles. What do the results of the study mean? This study highlights the potential significance of serum sodium levels as a predictor of treatment effectiveness in mCRC patients. Further research is needed to confirm these findings and better understand the underlying mechanisms. Evaluating serum sodium levels could be a useful tool in predicting outcomes and improving treatment strategies for mCRC patients.

Clinical outcome and safety profile of metastatic pancreatic cancer patients treated with more than six cycles of nab-paclitaxel plus gemcitabine.

The phase III MPACT trial demonstrated the superiority of gemcitabine plus nab-paclitaxel (NABGEM) versus gemcitabine alone in previously untreated patients with metastatic pancreatic cancer (mPC). The aim of this study was to evaluate the responses in terms of efficacy and safety in patients treated with more than 6 cycles of chemotherapy. From January 2015 to December 2018, patients with mPC receiving first-line treatment with NABGEM were included in a multicentre retrospective observational study. Exploratory analyses of efficacy and safety were performed. The cohort included 153 patients with performance status of 1. The median overall survival and progression-free survival were 20 months (hazard ratio [HR] 0.28, 95% confidence interval [CI]: 0.17-0.44) and 10 months (HR 0.24 95% CI: 0.16-0.38) respectively, in patients who received >6 cycles compared to 9 and 5 months in those treated with ≤6 cycles (p < 0.001). The disease control rate was 100% versus 56% in patients receiving >6 and ≤6 cycles, respectively. No progression of disease was recorded in patients who received >6 cycles. Grade 1 neuropathy and grade 3 neutropenia were more frequent in patients treated with >6 cycles compared to patients receiving ≤6 cycles (p = 0.01; p = 0.03, respectively). Dose reduction was necessary for 70.1% and 53.4% of patients treated with >6 or ≤6 cycles, whereas treatment interruption occurred in 37.1% and 21.6%, respectively. Our results confirmed the efficacy and safety of NABGEM in untreated mPC. In particular, we highlighted significant clinical efficacy in patients who received >6 cycles of chemotherapy compared to those who received ≤6 cycles, with manageable toxicity profile.

Prognostic value of alkaline phosphatase and gamma-glutamyl transferase in patients with metastatic pancreatic cancer.

Background: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. This study evaluated the prognostic role of serum alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT) in metastatic PC patients. Materials & methods: 153 patients with metastatic PC receiving first-line treatment with nab-paclitaxel/gemcitabine were retrospectively enrolled in a multicenter study and stratified according to ALP (≤ or >260 U/l) and GGT (≤ or >45.5 U/l) levels. Results: Improved overall survival was recorded in patients with GGT levels ≤45.5 U/l (p < 0.05). In patients with liver metastasis, overall survival was significantly lower in patients with high ALP (p = 0.01) and GGT (p = 0.02). Conclusion: High levels of ALP and GGT were related to a poor prognosis in PC patients with liver metastasis receiving nab-paclitaxel/gemcitabine.

Pancreatic cancer is a deadly form of cancer. This study looked at whether levels of two enzymes, alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT), in the blood of patients with metastatic pancreatic cancer could predict how long they would live. The study included 153 patients who were receiving their first treatment for metastatic pancreatic cancer. The patients were divided into groups based on whether their ALP and GGT levels were high or low. The researchers found that patients with low GGT levels tended to live longer. Patients with liver metastasis (spread of cancer to the liver) who had high levels of ALP and GGT tended to have a worse prognosis than patients with low levels of these enzymes. Therefore, higher levels of ALP and GGT in the blood may be associated with a poor prognosis in pancreatic cancer patients with liver metastasis who are receiving nab-paclitaxel/gemcitabine treatment.

The impact of age, performance status and comorbidities on nab-paclitaxel plus gemcitabine effectiveness in patients with metastatic pancreatic cancer.

Few studies have evaluated the impact of risk factors such as performance status (PS) and comorbidities on overall survival (OS) in patients with metastatic pancreatic cancer (mPC). We investigated the influence of comorbidity, PS and age on nab-paclitaxel and gemcitabine (NabGem) effectiveness profile in naive patients with mPC. 153 patients with mPC treated with NabGem upfront was divided in three groups (score 0 to 3) based on the absence or the presence of one or more risk factors among: age ≥ 70 years, PS 1 and comorbidities and the clinical outcomes was compared. Fifty-five patients were elderly (≥ 70 years), 80 patients have PS 1, whereas the other have PS 0. Patients with no risk factors (score 0) had an overall survival higher (20 months) than patients with one or two risk factors (score 1-2) (OS 11 months) and with three risk factors (score 3) (OS 8 months) (p < 0.01). The difference in OS was also statistically significant in patients without comorbidities (OS 15 months) compared to those with ≥ 1 comorbidity (OS 10 months) (p < 0.001). NabGem chemotherapy represent an effective treatment in naive patients. Age, PS, and comorbidities were prognostic factors in patients with metastatic pancreatic cancer.

Risk Factors for Nab-Paclitaxel and Gemcitabine-Induced Peripheral Neuropathy in Patients with Pancreatic Cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent adverse events observed with taxane use, whose disability often required modification or treatment discontinuation. The aim of this study was to assess the value of several variables as risk factors for CIPN development. MATERIAL AND METHODS: Eligible patients with metastatic pancreatic cancer receiving chemotherapy with nab-paclitaxel and gemcitabine were assessed in a multicenter study. Peripheral neuropathy was categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02, and a physical/neurological examination. Univariate and multivariate regression analyses were used to identify blood-based and clinical factors associated with CIPN. RESULTS: Data were available from 153 patients from five Italian centers. Key risk factors of CIPN in univariate regression models included age, number of chemotherapy cycles, statin assumption, and concomitant comorbidities. However, in the multivariate analysis, only for age (OR 1.0, p < 0.01, 95% CI: 1.01-1.11) and the number of cycles (OR 1.22, p < 0.01, 95% CI: 1.09-1.36), the correlation with CIPN development has been confirmed. CONCLUSION: Our study confirms age and the number of chemotherapy cycles as CIPN risk factors. The identification and validation of different risk factors could be advantageous to prevent or optimize management of CIPN which outstandingly affect the patient's quality of life.

Association between Low-Grade Chemotherapy-Induced Peripheral Neuropathy (CINP) and Survival in Patients with Metastatic Adenocarcinoma of the Pancreas.

The combination of nab-paclitaxel and gemcitabine demonstrated greater efficacy than gemcitabine alone but resulted in higher rates of chemotherapy-induced peripheral neuropathy (CINP) in patients with metastatic pancreatic cancer (mPC). We aimed to evaluate the correlation between the development of treatment-related peripheral neuropathy and the efficacy of nab-P/Gem combination in these patients. mPC patients treated with nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 as a first-line therapy were included. Treatment-related adverse events, mainly peripheral neuropathy, were categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02. Efficacy outcomes, including overall survival (OS), progression-free survival (PSF), and disease control rate (DCR), were estimated by the Kaplan-Meier model. A total of 153 patients were analyzed; of these, 47 patients (30.7%) developed grade 1-2 neuropathy. PFS was 7 months (95% CI (6-7 months)) for patients with grade 1-2 neuropathy and 6 months (95% CI (5-6 months)) for patients without peripheral neuropathy (p = 0.42). Median OS was 13 months (95% CI (10-18 months)) and 10 months (95% CI (8-13 months)) in patients with and without peripheral neuropathy, respectively (p = 0.04). DCR was achieved by 83% of patients with grade 1-2 neuropathy and by 58% of patients without neuropathy (p = 0.03). In the multivariate analysis, grade 1-2 neuropathy was independently associated with OS (HR 0.65; 95% CI, 0.45-0.98; p = 0.03). nab-P/Gem represents an optimal first-line treatment for mPC patients. Among possible treatment-related adverse events, peripheral neuropathy is the most frequent, with different grades and incidence. Our study suggests that patients experiencing CINP may have a more favorable outcome, with a higher disease control rate and prolonged median survival compared to those without neuropathy.

The value of patient centred care in oncology.

The value of health care should be measured as the patient's well-being. This demands knowledge of patient's preference. Communication, i.e. delivering messages which can be understood + taking on board requests and priorities) is a complex exercise; even more when interacting with senior patients. It must be a primary career's privilege to satisfy his/her patient's requests however; we have much to improve in our interaction with senior cancer patients.

Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer.

Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5-8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5-6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10-18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8-13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09-0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

FOLFOX vs FOLFIRI as Second-line of Therapy After Progression to Gemcitabine/Nab-paclitaxel in Patients with Metastatic Pancreatic Cancer.

BACKGROUND: Several progresses have been achieved for first-line chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with Gem-NabP and FOLFIRINOX extensively used as standard first line regimens. However, the best second-line chemotherapy choice after progression is still not completely defined. The aim of this study is to compare effectiveness and safety of two possible second-line therapeutic options, FOLFOX and FOLFIRI, after progression to Gem-NabP. METHODS: From January 2015 to December 2018, patients with metastatic PDAC, progressed to the first-line treatment with Gem-NabP, and treated with a fluoropyrimidine-based second-line chemotherapy were considered eligible for our retrospective analysis. Overall survival (OS) and progression free survival (PFS) were set as primary endpoints whereas, disease control rate (DCR) and the rate and severity of treatment-related AEs were secondary endpoints. RESULTS: Overall, 31 patients were treated with Gem-NabP in first-line regimen, 11 received second-line with FOLFOX and 20 with FOLFIRI after progression. Baseline demographic and clinic features were similar in the two groups excluding median age of 55.5 years (range: 50-73) and 68 years (range: 59-72) in FOLFIRI and FOLFOX groups, respectively (p=0.002). Median PFS was three months (95%CI: 3-4), with no significative difference between the two groups. Median OS was eight months (95%CI: 5-10) and was significantly higher in the FOLFIRI group compared with the FOLFOX group, nine months (95%CI: 7-17) vs five months (95%CI: 2-10; p<0.01). The most commonly reported adverse events were grade 1 or 2 with anemia most frequent in the FOLFOX group (36.4% vs 10.0%) and diarrhea in the FOLFIRI group (40.0% vs 9.1%). Grade 3-4 adverse events as neutropenia, diarrhea and nausea/vomiting, occurred in 10 patients (32.2%) without differences between the two groups. CONCLUSION: Our results seem to support the use of fluoropyrimidine-based second-line therapy for patients with metastatic pancreatic cancer, confirming the effectiveness and safety, to a greater extent with FOLFIRI regimen, after progression to the Gem-NabP.

Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study.

BACKGROUND: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. METHODS: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. RESULTS: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. CONCLUSION: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

Surgical oncology in the elderly.

Poor cancer-specific outcomes in the elderly group are primarily a surgical failure. Surgeons are insufficiently trained to draw a line between fit and frail patients; this results in over-treatment of the frail patient, as well as under-treatment of the fit one. Communication skills should be improved to better understand the patient's requests. The timing of the surgical procedure is crucially important; all efforts should be put in place to optimize the patient's conditions before the surgery takes place.

"Understanding older patients: Communication as the key step for a comprehensive approach".

Patient's frailty, attitude, life expectancy, affect the decision-making process, impacting on the following four points: 1.Disclosing the diagnosis. 2.Discussing treatment options and prognosis. 3.Tailoring treatment. 4.Assisting patients along their recovery. Setting up an open, frank, transparent and informative discussion is the key step in addressing a patient-centered treatment plan. Our recommendations are summarized in the following pages.

Information given to cancer patients on diagnosis, prognosis and treatment: the clinical oncologist's perspective.

The extent of information to cancer patients is, in general, culture-dependent. Information mainly refers to three aspects, namely diagnosis (Dx), prognosis (Px) and treatment (Rx), but the relative contribution of each domain to the information given overall is not available. To address this issue, we e-mailed a questionnaire to 9893 members of the American Society of Clinical Oncology (ASCO) asking whether they agree that information about Dx, Px and Rx contribute differently to the information given to the cancer patient overall and, if so, to what extent, both in the adjuvant and advanced settings. 857 questionnaires were evaluable. There was no statistically significant difference between the contribution of these 3 domains in the adjuvant setting (33%, 34% and 33%, respectively). In subgroup analysis, medical oncologists and haematologists attributed a significantly higher contribution of Px information compared with other specialists (P < 0.05). In the advanced setting, respondents estimated a higher contribution of Px (41%) to patient information overall compared with Dx and Rx (28% and 31%, respectively; P < 0.05). This finding was more pronounced in North America than in Europe (P < 0.0001), and in Germanic-language than in Romance-language countries (P = 0.005). In conclusion, information on Dx, Px and Rx are believed to contribute differently to the information delivered to cancer patients overall, depending on the stage of disease, the cultural environment and the specialty of the physician.