Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVIDENCE study.

BACKGROUND: Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs). METHODS: We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion. RESULTS: Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85). CONCLUSION: The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.

Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials.

Background & Aims: Direct comparisons across first-line regimens for advanced hepatocellular carcinoma are not available. We performed a network metanalysis of phase III of trials to compare first-line systemic treatments for hepatocellular carcinoma in terms of overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate, and incidence of adverse events (AEs). Methods: After performing a literature review from January 2008 to September 2022, we screened 6,329 studies and reviewed 3,009 studies, leading to identification of 15 phase III trials for analysis. We extracted odds ratios for objective response rate and disease control rate, relative risks for AEs, and hazard ratios (HRs) with 95% CIs for OS and PFS, and used a frequentist network metanalysis, with fixed-effect multivariable meta-regression models to estimate the indirect pooled HRs, odds ratios, relative risks, and corresponding 95% CIs, considering sorafenib as reference. Results: Of 10,820 included patients, 10,444 received active treatment and 376 placebo. Sintilimab + IBI350, camrelizumab + rivoceranib, and atezolizumab + bevacizumab provided the greatest reduction in the risk of death compared with sorafenib, with HRs of 0.57 (95% CI 0.43-0.75), 0.62 (95% CI 0.49-0.79), and 0.66 (95% CI 0.52-0.84), respectively. Considering PFS, camrelizumab + rivoceranib and pembrolizumab + lenvatinib were associated with the greatest reduction in the risk of PFS events compared with sorafenib, with HRs of 0.52 (95% CI 0.41-0.65) and 0.52 (95% CI 0.35-0.77), respectively. Immune checkpoint inhibitor (ICI) monotherapies carried the lowest risk for all-grade and grade ≥3 AEs. Conclusions: The combinations of ICI + anti-vascular endothelial growth factor, and double ICIs lead to the greatest OS benefit compared with sorafenib, whereas ICI + kinase inhibitor regimens are associated with greater PFS benefit at the cost of higher toxicity rates. Impact and Implications: In the last few years, many different therapies have been studied for patients with primary liver cancer that cannot be treated with surgery. In these cases, anticancer drugs (alone or in combination) are given with the intent to keep the cancer at bay and, ultimately, to prolong survival. Among all the therapies that have been investigated, the combination of immunotherapy (drugs that boost the immune system against the cancer) and anti-angiogenic agents (drugs that act on tumoural vessels) has appeared the best to improve survival. Similarly, the combination of two types of immunotherapies that activate the immune system at different levels has also shown positive results. Systematic Review Registration: PROSPERO CRD42022366330.

Impact of adjuvant imatinib on bone and muscle density in patients with resected gastrointestinal stromal tumors.

Adjuvant treatment with Imatinib is the standard of care for high-risk resected GISTs. Imatinib is known to have an impact on bone mineral density in patients affected by chronic myeloid leukemia, however this effect has never been investigated in GISTs. We retrospectively evaluated, on CT scans, the effect of adjuvant Imatinib (400 mg/die) on bone mineral density and muscle composition in 14 patients with surgically resected GISTs and in a control group of 8 patients who did not received any treatment. The effect of bone and muscle composition on Imatinib-tolerance was assessed as well. Overall patients receiving Imatinib experienced an increase in bone mineral density during treatment (p = 0.021); with higher increase in patients with basal values < 120 mg/cm3 (p = 0.002). No changes were observed in the control group (p = 0.918). Skeletal muscle index and lean body mass did not change over time during Imatinib therapy; however, patients with lower lean body mass and lower body mass index experienced more grade 3 treatment related toxicities (p = 0.024 and p = 0.014 respectively). We also found a non-significant trend between basal BMD and grade 3 toxicities (p = 0.060).

S-Adenosylmethionine Supplementation May Reduce Cancer-Related Fatigue: A Prospective Evaluation Using the FACIT-F Questionnaire in Colon Cancer Patients Undergoing Oxaliplatin-Based Chemotherapy Regimens.

BACKGROUND: Fatigue is a common distressing symptom for patients living with chronic or acute diseases, including liver disorders and cancer (Cancer-Related Fatigue, CRF). Its etiology is multifactorial, and some hypotheses regarding the pathogenesis are summarized, with possible shared mechanisms both in cancer and in chronic liver diseases. A deal of work has investigated the role of a multifunctional molecule in improving symptoms and outcomes in different liver dysfunctions and associated symptoms, including chronic fatigue: S-adenosylmethionine (SAM; AdoMet). The aim of this work is actually to consider its role also in oncologic settings. PATIENTS AND METHODS: Between January 2006 and December 2009, at the University Campus Bio-Medico of Rome, 145 patients affected by colorectal cancer in adjuvant (n = 91) or metastatic (n = 54; n = 40 with liver metastases) setting and treated with oxaliplatin-based regimen (FOLFOX for adjuvant and bevacizumab + XELOX for metastatic ones), 76 of which with the supplementation of S-adenosylmethionine (AdoMet; 400 mg b.i.d.) (57% of adjuvant patients and 44% of metastatic ones) and 69 without AdoMet supplementation, were evaluated for fatigue prevalence using the Functional Assessment of Chronic Illnesses Therapy-Fatigue (FACIT-F) questionnaire, at 3 and 6 months after the beginning of oncologic treatment. Notably, the number of patients with liver metastases was well balanced between the group of patients treated with AdoMet and those who were not. RESULTS: Among patients receiving oxaliplatin-based chemotherapy, both in adjuvant and in metastatic settings, after just 3 months from the beginning of chemotherapy, mean scores from questionnaire domains like FACIT-F subscale (7.9 vs. 3.1, p = 0.006), FACIT physical (6.25 vs. 3.32, p = 0.020), FACIT emotional (4.65 vs. 2.19, p = 0.045), and FACIT-F total score (16.5 vs. 8.27, p = 0.021) were higher in those receiving supplementation of AdoMet, resulting in reduced fatigue; a significant difference was maintained even after 6 months of treatment. DISCUSSION AND CONCLUSIONS: Mechanisms and strategies for managing CRF are not fully understood. This work aimed at investigating the possible role of S-adenosylmethionine supplementation in improving fatigue scores in a specific setting of cancer patients, using a FACIT-F questionnaire, a well-validated quality of life instrument widely used for the assessment of CRF in clinical trials.

Denosumab for cancer-related bone loss.

INTRODUCTION: Prolonged use of anti-cancer treatments in breast and prostate tumors alters physiological bone turnover leading to adverse skeletal related events, such as osteoporosis, loss of bone mass, and increased risk of fractures. These complications known as cancer treatment-induced bone loss (CTIBL) should be managed with bone targeting agents such as the bisphosphonates and denosumab. The latter is a monoclonal antibody against the receptor activator of nuclear factor-kB ligand (RANKL) that suppresses osteoclasts function and survival increasing bone mass. AREAS COVERED: This review will focus on the mechanisms associated with bone loss induced by cancer treatments and the most recent evidence about the use of denosumab as preventive and therapeutic strategy to protect bone health. Moreover, we will discuss several key aspects regarding the clinical practical use of denosumab to optimize the management of CTLIB in breast and prostate cancer. EXPERT OPINION: Denosumab treatment strongly prevents cancer therapies-related skeletal issues in breast and prostate cancer with a good safety profile. Adjuvant six-monthly denosumab delays the time to first fracture onset in early stage breast cancer patients with normal or altered bone mineral density (BMD). Similarly, denosumab treatment is able to prevent fractures and BMD loss in nonmetastatic prostate cancer patients.

Anticancer activity of "Trigno M", extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models.

In 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style : a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phytochemicals to have an inhibiting effect on the growth of various cancers through the activation of apoptosis. Our goal was to prove the effectiveness of a natural compound in the combined therapy of colorectal cancer. Trigno M supplement was an optimal candidate as anticancer product for its high concentrations of phenolic acids, flavonoids and anthocyanins. Our work showed the antitumor activity of Trigno M, extract of Prunus spinosa drupes combined with the nutraceutical activator complex (NAC), in 2D, 3D and in vivo colorectal cancer models. The cellular model we used both in vitro and in vivo was the HCT116 cell line, particularly suitable for engraftment after inoculation in mice. Trigno M inhibited the growth and colony formation of HCT116 cells (35%) as compared to the chemotherapy treatment with 5-fluorouracil (80%) used in clinical therapy. The reduction of the morphological dimensions in the spheroid cells after Trigno M, was compared with 5-fluorouracil demonstrating the efficacy of the Trigno M compound also in 3D models. Flow cytometric analysis on 3D cells showed a significant increase in the apoptotic cell fraction after Trigno M treatment (44.8%) and a low level of necrotic fraction (6.7%) as compared with control cells. Trigno M and 5-fluorouracil induced the apoptosis in a comparable percentage. Monotherapy with Trigno M in severely immunodeficient mice, carrying colon rectal cancer xenografts, significantly reduced tumor growth. The histopatological analysis of the ectopic tumors showed a lower level of necrosis after Trigno M treatment compared with the control. We conclude that Trigno M is well tolerated by mice, delays colorectal cancer growth in these animals and should be weighed up for integration of the current multi-drug protocols in the treatment of colon carcinoma.

Risk of pruritus in cancer patients treated with biological therapies: A systematic review and meta-analysis of clinical trials.

BACKGROUND: Pruritus has been described with targeted therapies in cancer patients. We performed an up-to-date meta-analysis to determine the incidence and RR in patients with cancer treated with these agents. METHODS: PubMed databases were searched for articles published till October 2014. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. FINDINGS: A total of 4803 potentially relevant trials were identified; of them, 33 randomized phase III studies were included in this meta-analysis; 20,151 patients treated with 14 distinct targeted agents were available for this analysis; 8816 (44%) had Non-small cell lung cancer (NSCLC) and 12,257 had other malignancies. The highest incidences of all-grade pruritus were observed with panitumumab (56.8) and gefitinib (49.4), while the lowest incidences were reported by erlotinib (3.6) and sunitinib (5.8). In addition, the highest incidence of high-grade pruritus was reported by gefitinib (5.9). The summary RR of developing all-grade and high-grade pruritus with targeted agents vs. controls were 2.2 and 2.6, respectively. The highest RRs of all-grade pruritus were associated with panitumumab (25.6) and ipilimumab (4.5). Grouping by drug category, the RR of all-grade pruritus with anti-EGFR mAbs was 2.84 (95% CI 2.39 to 3.37) compared to anti-EGFR/HER2 TKIs and 1.24 (95% CI 1.03 to 1.49) to immunotherapy. INTERPRETATION: Treatment with biological therapy in cancer patients is associated with a significant increase in the risk of pruritus, and frequent clinical monitoring of pruritus should be emphasized when managing these and newer targeted agents.

Liver toxicity in colorectal cancer patients treated with first-line FOLFIRI-containing regimen: a single institution experience.

BACKGROUND: Chemotherapy-induced toxic liver injury is a relevant issue in the clinical management of patients affected with metastatic colorectal cancer (mCRC). This retrospective study evaluated patterns of liver toxicity in patients treated with FOLinic acid, Fluorouracil, IRInotecan (FOLFIRI)-based regimens. METHODS: One hundred and fifty-six mCRC patients treated at the University Campus Bio-Medico between January 2003 and January 2013 were included in this retrospective analysis. All patients received a FOLFIRI backbone-based chemotherapy. Basal liver enzymes levels were assessed before starting the treatment and before every therapy course. R ratio and the aspartate aminotransferase/alanine aminotransferase ratio were calculated. RESULTS: Ninety-one patients were male versus 55 female, and the median age of the population was 62 years (range: 38-83). Most patients had liver involvement at the beginning of first-line regimen (101 patients, 64.74%) and 59 patients had received a previous 5-FU based therapy in the adjuvant setting (37.82%). Aspartate aminotransferase level (167.87 vs 41.05 U/l; p < 0.001), Alanine aminotransferase level (94.48 vs 39.80 U/l; p = 0.004) and alkaline phosphatase (289.0 vs 172.44 U/l; p = 0.02) were significantly increased during the first 3 months of treatment. In the entire population, the calculated R ratio was 3.96 (95% CI: 3.25-4.51). In all three regimens, the calculated R ratio was between 2 and 5, without any statistical differences. CONCLUSIONS: FOLFIRI-based hepatotoxicity has been indirectly defined as a mixed pattern injury in all three regimens evaluated.

Genetic modulation of the interleukin 6 (IL-6) system in patients with advanced gastric cancer: a background for an alternative target therapy.

BACKGROUND: IL-6 triggers oncogenic/angiogenic signals and the cytokine-dependent pro-cachexia cascade. The prognostic role of the functional IL-6 (promoter) rs1800795 and the IL-6R (receptor) rs8192284 single nucleotide polymorphisms (SNP) was studied in patients with advanced gastric cancer treated with palliative chemotherapy. METHODS: One-hundred-sixty-one patients were genotyped for rs1800795 and rs8192284 SNPs using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis assay. These results were studied for association with overall survival (OS). RESULTS: In 161 assessable patients, frequencies of rs1800795 G/G, G/C and C/C genotypes were 46%, 42% and 12%, respectively. Frequencies of rs8192284 A/A, A/C and C/C genotypes were 36%, 45% and 19%, respectively. Carriers of the rs1800795 G/G and rs8192284 C/C genotypes showed the worst OS. In the multivariate model, rs1800795 G/G (1.69 hazard ratio; 95% confidence interval 1.18-2.42), and rs8192284 C/C (1.78 hazard ratio; 95% confidence interval 1.12-2.83) confirmed an adverse prognostic impact. CONCLUSIONS: In this population, genetic variants that up-regulate the IL-6 system showed impact on OS. This findings sustain the hypothesis that anti-IL-6 compounds deserve clinical studies as novel therapeutics in the palliative treatment of cancer patients.

Sorafenib in elderly patients with advanced hepatocellular carcinoma: a case series.

OBJECTIVE: The management of hepatocellular carcinoma (HCC) in elderly patients is significantly more complicated than in younger patients because of medical comorbidities, advanced status at diagnosis, reduced liver function and altered drug pharmacokinetics. Our objective was a revision of the charts of unselected elderly patients with HCC being treated with a reduced starting dose of sorafenib. METHODS: Activity, adverse events and quality of life were evaluated during the treatment. Sixty patients (47 males and 13 females) aged more than 70 years old (range 70-90, median 76 years) were retrospectively reviewed. RESULTS: One complete and one partial response were achieved in the series (overall response rate 3.3%). Stable disease accounted for 76.6% (46 out of 60 patients). The disease control rate (complete plus partial response plus stable disease) was 80%. Median time to progression (TTP) was 7.0 months (95% CI, 5.2-8.7 months) and median survival was 10.0 months (95% CI, 5.0-14.9 months). Thrombosis correlated to TTP. Full doses of sora-fenib were reached in 11 out of 60 patients (18.3%). The evaluation of quality of life did not show any significant change during the study. CONCLUSIONS: Sorafenib at a reduced dose can be safely used in elderly HCC patients with maintenance of activity and increased tolerability.

Identification of clinical predictive factors of oxaliplatin-induced chronic peripheral neuropathy in colorectal cancer patients treated with adjuvant Folfox IV.

PURPOSE: Oxaliplatin-induced neuropathy is a dose-related side effect which occurs in almost 40 % of patients treated with oxaliplatin. Aim of the present study was to identify reliable clinical factors predicting its development and duration. METHODS: One hundred sixty-nine completely resected colorectal cancer patients treated with adjuvant Folfox IV regimen were retrospectively included. The following pre-treatment clinical parameters were collected: hypocalcaemia, hypomagnesaemia, hypoalbuminaemia, anaemia, diabetes, chronic renal failure (CRF), folate deficiency, vitamin B(12) deficiency, number of cycles received and habit to alcohol consumption. Incidence, grade (NCI-CTCAE v.3) and duration of neuropathy were recorded. RESULTS: Incidence of neuropathy was found to be higher in patients with pre-treatment anaemia (p = 0.001), hypoalbuminaemia (p = 0.01) and hypomagnesaemia (p = 0.001) as well in those with habit to alcohol consumption (p = 0.003). Neuropathy durations were conversely associated with age, being longer in younger patients (p = 0.03), and again with hypoalbuminaemia (p = 0.04) and hypomagnesaemia (p = 0.002). No correlation was found with gender, hypocalcaemia, diabetes and CRF. The correlation between vitamin B(12) and folate levels and the development of neurotoxicity were not analysed because of the high number of missing data in the population. CONCLUSIONS: Age, anaemia, hypoalbuminaemia, hypomagnesaemia and alcohol consumption are reliable and easily assessable clinical factors predicting incidence and length of oxaliplatin-induced neuropathy.

Sorafenib and dacarbazine in soft tissue sarcoma: a single institution experience.

BACKGROUND: To report on the anti-tumour activity and toxicity of sorafenib combined with dacarbazine in patients with pre-treated advanced soft tissue sarcoma (STSs). METHODS: From November 2009 to December 2010, 17 patients affected by STSs who had failed two or more regimen of chemotherapy, with a performance status ≤ 2 and measurable disease were consecutively enrolled in the present case series. Sorafenib was administered at 400 mg b.i.d. continuous dosing in combination with dacarbazine, 300 mg/m(2) for three consecutive days every 21 days until disease progression or intolerable toxicity. RESULTS: Fourteen patients were evaluable for response. Three patients stopped treatment early and were not evaluable for response. One of them died for not disease-dependent reason, the other two went off-study due to rapid clinical worsening, without performing radiologic evaluation. No complete responses were registered. As by RECIST, partial responses (PR) were observed in three patients (21%), stable disease (SD) in six patients (43%) and progressive disease (PD) in five patients (36%), with a clinical benefit rate (RECIST PR+SD > 6 months) of 64%. The median time of progression was 20 weeks (range: 9 - 34 weeks) and the median overall survival was 43 weeks (range: 17 - 65 weeks). The main toxicities were neutropenia (36%), thrombocytopenia (36%), hypertension (36%), fatigue (50%) and skin reactions (57%). Five patients required dose reductions (both dacarbazine and sorafenib) for toxicity and three patients required only sorafenib reduction for dermatologic reactions. One patient was taken off-study because of severe sorafenib-related dermatologic toxicity. CONCLUSIONS: Sorafenib and dacarbazine combination seems to be an active and safety regimen in pre-treated STSs. A Phase II trial is ongoing in patient affected by selected sarcoma subtypes.

Exploring the efficacy and safety of single-agent sorafenib in a cohort of Italian patients with hepatocellular carcinoma.

This study investigates the effectiveness and safety of sorafenib in a heterogeneous cohort of Child-Pugh A, B and C patients with advanced hepatocellular carcinoma in a clinical-practice scenario. Adult patients with hepatocellular carcinoma and treated with sorafenib 800 mg/day were eligible for this multicentric retrospective observational study. Safety analyses were performed and the effectiveness of sorafenib was assessed in terms of time to progression (TTP) and overall survival (OS). In total, 93 patients were enrolled: 14 were Child-Pugh A, 70 were Child-Pugh B and nine were Child-Pugh C. No differences in the frequency of grade 3 adverse events among different Child-Pugh classes were reported. In the overall cohort, median OS was 12 months (95% CI: 11.7-12.8 months) and TTP was 3 months (95% CI: 2.5-3.4 months). The Child-Pugh score had a statistically significant effect on TTP: 6.6 months in Child-Pugh A, 2.8 months in Child-Pugh B and 2.0 months in Child-Pugh C patients (p = 0.012). To our knowledge, this study includes the largest cohort of Caucasian Child-Pugh B and C patients ever treated with sorafenib. Although the retrospective design of this study does not allow reaching any definite conclusion, the results could lend some preliminary support to the safety and the effectiveness of sorafenib monotherapy in patients with Child-Pugh B and Child-Pugh C liver function.

The role of S-adenosylmethionine in preventing oxaliplatin-induced liver toxicity: a retrospective analysis in metastatic colorectal cancer patients treated with bevacizumab plus oxaliplatin-based regimen.

BACKGROUND: Hepatotoxicity represents a frequent chemotherapy-related side effect, often associated with course delays, discontinuations, and dose reductions. S-adenosylmethionine (AdoMet) administration is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced damage. PATIENTS AND METHODS: Seventy-eight patients affected by metastatic colorectal cancer were enrolled. Forty-two patients were treated with bevacizumab and XELOX without administering AdoMet, 32 were treated with the same regimen plus supplementation with AdoMet. Liver enzymes levels were assessed before starting the treatment, and then every therapy cycle, liver toxicity, chemotherapy course delays, discontinuations, and dose reductions due to liver toxicity were recorded. RESULTS: Aspartate aminotransferase (P = 0.02), alanine transaminase (P < 0.001), lactate dehydrogenase (P = 0.008), total bilirubin (P = 0.03), and gamma-glutamyltransferase (P < 0.001) were found to be significantly lower in patients treated with AdoMet than in those who were not. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (P = 0.009) and had a reduced need of course delay (P = 0.042) and dose reduction (P = 0.051). CONCLUSIONS: AdoMet supplementation in patients affected by metastatic colorectal cancer treated with oxaliplatin-based regimen seems to be effective in the prevention of chemotherapy-induced liver injury.

The role of S-adenosyl methionine in preventing FOLFOX-induced liver toxicity: a retrospective analysis in patients affected by resected colorectal cancer treated with adjuvant FOLFOX regimen.

BACKGROUND: Hepatic toxicity is often related to chemotherapy agent administration, and it represents one of the principal causes of dose reduction and chemotherapy delays or discontinuation. S-Adenosyl methionine (AdoMet) supplementation is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced liver damage. PATIENTS AND METHODS: A total of 105 patients affected by resected colorectal cancer (CRC) were enrolled. Forty-five were treated with FOLFOX IV adjuvant regimen without administering AdoMet, 60 were treated with the same regimen plus supplementation with AdoMet. Liver enzyme levels were assessed before starting the treatment and every therapy cycle. Liver toxicity, chemotherapy course delays, discontinuations and dose reductions due to liver toxicity were recorded. RESULTS: Aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p = 0.003), bilirubin (p = 0.04) and gamma-glutamyltransferase (γ-GT) (p = 0.002) median level at the end of adjuvant therapy were significantly lower in patients treated with Adome. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (p = 0.002) and had a reduced need of course delay (p < 0.0001) and dose reduction (p = 0.031). CONCLUSIONS: The results of our study demonstrate a protective effect of AdoMet supplementation in patients affected by resected CRC treated with FOLFOX IV adjuvant regimen.

Targeting EGFR in bilio-pancreatic and liver carcinoma.

The key role of epidermal growth factor receptor(EGFR) in tumorigenesis has been demonstrated in several cancer types, so recent clinical trials have investigated their activity/efficacy in different settings. Two different types of EGFR-targeted agents were developed: monoclonal antibodies such as cetuximab and panitumumab, and tyrosine kinase inhibitors, such as gefitinib and erlotinib. In this review, we summarize the preclinical rational of potential activity and the most important clinical trials evaluated anti-EGFR targeted agents in non-colorectal digestive cancer, both in monotherapy and in combination with other chemotherapeutic or targeted agents. Patient selection by use of biologic markers will identify which patients are more likely to respond, contributing to the successful use of these agents.

Wide-spectrum characterization of trabectedin: biology, clinical activity and future perspectives.

Ecteinascidin-743 (trabectedin, Yondelis((R)); PharmaMar, Madrid, Spain), a 25-year-old antineoplastic alkylating agent, has recently shown unexpected and interesting mechanisms of action. Trabectedin causes perturbation in the transcription of inducible genes (e.g., the multidrug resistance gene MDR1) and interaction with DNA repair mechanisms (e.g., the nucleotide excision repair pathway) owing to drug-related DNA double strand breaks and adduct formation. Trabectedin was the first antineoplastic agent from a marine source (namely, the Caribbean tunicate Ecteinascidia turbinata) to receive marketing authorization. This article summarizes the mechanisms of action, the complex metabolism, the main toxicities, the preclinical and clinical evidences of its antineoplastic effects in different types of cancer and, finally, the future perspectives of this promising drug.

'If it is not recorded, it has not been done!'? consistency between nursing records and observed nursing care in an Italian hospital.

AIMS: The aim of this study is to evaluate the consistency between the care given to patients and that documented, by comparing care observations with nursing records and describing which interventions were reported and which were omitted. BACKGROUND: Assumptions have been made about the relationship between documentation and care actually delivered, but there is insufficient evidence on the relationship between the actual care given and its recording. DESIGN: Observational study of the care given, completed by interviews and retrospective survey of records. METHODS: Structured observation during day shifts in the first six days of admission of pre and postsurgical care provided to 21 consecutive patients undergoing major abdominal surgery and audit of their nursing records. Each observation was completed by short interviews to nurses to ensure observations validity. RESULTS: Only 40% of nursing activities observed were included in the nursing records (37% of the assessments and 45% of the interventions). This indicated that nurses carry out more activities than they report. Consistency between performed and recorded care decreased significantly during the days when a higher number of activities were performed. Consistency between recording and observation of assessment activities was 38% for physical needs and 0% for educational needs. Consistency was higher for the assessments of physical signs/symptoms and risk factors for complications compared to the assessment of basic needs and pain. Consistency was 47% for technical interventions and 3% for educational activities. CONCLUSIONS: Nursing records were not found to be an adequate tool for quality care evaluation, because they did not include all the caring activities that the nurses had carried out. RELEVANCE TO CLINICAL PRACTICE: This study supports the need to identify documentation systems that are easy to complete. Moreover, nursing education should pay more attention to the competences in the field of holistic care and patient education.

Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So.LAR. study.

PURPOSE: Advanced hepatocellular carcinoma (HCC) not eligible for local therapies has limited chances of cure. Sorafenib is a multikinase inhibitor with proven activity in advanced HCC. Octreotide is used in this setting with conflicting results. Treatment with sorafenib and long-acting octreotide was tested in advanced HCC to evaluate safety and activity. METHODS: Fifty patients with advanced HCC, Child-Pugh A or B, received sorafenib at a dosage of 800 mg/day for 28 days with a following week of rest and long-acting octreotide at a dose of 40 mg, administered every 28 days. RESULTS: All patients were assessable for safety and efficacy. Sixteen patients out of 50 (34%) were naïve from other therapies, while all the others were previously treated with local and/or systemic treatments. We achieved 5 partial responses (10%), 33 stable diseases (66%) and 12 progressions of disease (24%). Median time to progression was 7.0 months (95% CI, 3.0-10.9 months), and median overall survival was 12 months (95% CI, 6.3-17.4 months). Treatment was well tolerated. Diarrhoea (6%) and hypertension (4%) were the most frequent grade 3 toxicities. CONCLUSIONS: Our data suggest that the combination between sorafenib and long-acting octreotide is active and well tolerated in patients with advanced HCC and could represent another efficacious chance for the management of this population.