Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

BACKGROUND: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. PATIENTS AND METHODS: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. RESULTS: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. CONCLUSIONS: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy?

BACKGROUND: New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. METHODS: Retrospective analysis. EXCLUSION CRITERIA: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. RESULTS: 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). CONCLUSIONS: Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.

Panitumumab for the treatment of metastatic colorectal cancer: a review.

In recent years, the treatment of metastatic colorectal cancer (mCRC) has evolved significantly with the increase of new therapeutic options, leading to an improved median survival for these patients. In particular, the identification of molecular targets in tumor cells has led to the introduction of biological drugs for the treatment of mCRC. Panitumumab is a fully human monoclonal antibody that binds the EGF receptor of tumor cells and inhibits downstream cell signaling with antitumor effect on inhibition of tumor growth. Its use has been approved by randomized clinical trials as monotherapy in chemorefractory patients or combined with chemotherapy in the treatment of RAS wild-type mCRC, where it demonstrated a significant improvement in survival and response rate. The purpose of this review is to analyze the use and efficacy profile of panitumumab, particularly focusing on recently reported data on its use, and future perspectives in patients with mCRC.

VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line sunitinib.

BACKGROUND: Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients. METHODS: A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS. CONCLUSIONS: In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.

Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients.

BACKGROUND: Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab. METHODS: Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases. RESULTS: Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7). CONCLUSION: High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker.

Allele polymorphisms of tumor integrins correlate with peritoneal carcinosis capability of gastric cancer cells in radically resected patients.

BACKGROUND: Preclinical studies suggested that integrins are relevant for gastric cancer diffusion. We investigated integrins polymorphisms role in determining peritoneal carcinosis or hematogenous metastases in radically resected gastric cancer. PATIENTS AND METHODS: Integrins genotyping was carried out on pT3 radically resected gastric tumors recurring with either peritoneal-only carcinosis or hematogenous metastases. RESULTS: The following factors resulted independently associated with peritoneal carcinosis or hematogenous metastases: the A genotype of rs2269772 (ITGA3) [odds ratio (OR) for peritoneal carcinosis: 22.2, 95% confidence interval 1.2-40, P=0.03], the G genotype of rs2269772 (ITGA3) (OR for hematogenous metastases: 5.5, 95% confidence interval 2.2-14.15, P=0.0003), the C genotype of rs11902171 (ITGV) (OR for peritoneal carcinosis: 6.8, 95% confidence interval 1.3-33.4, P=0.01), the G genotype of rs11902171 (ITGV) (OR for hematogenous metastases: 2.5, 95% confidence interval 1.1-5.7, P = 0.02), diffuse histology (OR for peritoneal carcinosis: 4.7, 95% confidence interval 1.9-11.3, P=0.0005) and intestinal histology (OR for hematogenous metastases: 4.2, 95% confidence interval 1.9-9.9, P=0.0008). CONCLUSIONS: Tumor histology represents a crucial issue conditioning tumoral behavior; genotyping of rs2269772 (ITGA3) and rs11902171 (ITGV) may be a further asset in the definition of high-risk patients for peritoneal carcinosis among those relapsing after curative resection. The selection tool deriving from this analysis may allow an optimal use of innovative treatment strategies.

Chemotherapy for locally advanced and metastatic gastric cancer: state of the art and future perspectives.

Despite a decline in the incidence in Western countries, gastric cancer is still the second most common cause of cancer-related death worldwide. Many advances have been made in diagnosis and treatment of gastric cancer in the last decades but the prognosis for gastric cancer patients remains disappointing, especially in more advanced stages. The poor outcome associated with surgical resection with curative intent has generated intensive investigation of combined modality treatment approaches including systemic chemotherapy and radiotherapy to prevent recurrences and improve survival. In this setting the use of perioperative chemotherapy or postoperative chemoradiotherapy has demonstrated to give survival benefits. In advanced disease, major improvements of the last years are represented by the introduction of oral fluoropyrimidines and drugs such as docetaxel or irinotecan and the demonstration of efficacy of the anti-HER2 agent trastuzumab.

[Influence of technological processes on the extractability of phenols and carbohydrates from sunflower meal and related protein solubility]. / Influenza dei trattamenti industriali sulla estraibilità di fenoli e carboidrati da farina di girasole e relativa solubilità delle proteine

A chemical method for the removal of chromogenic phenolic constituents and carbohydrates of the sunflower meal has been investigated. This method uses a nondenaturing polar solvent formed by n-butanol saturated by diluite HCl and allows the preparation of protein isolate off-colour free. Evaluations on the extractibility of phenols, carbohydrates and proteins of sunflower meals from different technological processes have been carried out.