translational challenges from the 2014 gastrointestinal cancers symposium toward a true tailored therapy through effective research

Gastrointestinal Cancers Symposium 2014, San Francisco, CA, USA, 16–18 January 2014 The Gastrointestinal Cancers Symposium represents an indisputable occasion for sharing results and research opportunities for investigators around the globe. Across the years along with clinical trials presentations the meeting increasingly acquired a distinct role as a scientific arena for translational research. Also, this year the need for predictive markers for first-generation targeted agents and research about novel biologically driven therapeutic options characterized most of the studies presented. We focus here on reports from the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium indicating an opportunity for biological selection of either the pharmacological target or the patient population in order to enhance clinical outcome

Exploratory findings from a prematurely closed international, multicentre, academic trial: RAVELLO, a phase III study of regorafenib versus placebo as maintenance therapy after first-line treatment in RAS wild-type metastatic colorectal cancer

Background In patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the role of maintenance therapy after first-line treatment with chemotherapy plus antiepidermal growth factor receptor (EGFR) monoclonal antibodies (MoAb) is still an object of debate. Methods We assessed the efficacy and safety of regorafenib as a switch maintenance strategy after upfront 5-fluorouracil-based chemotherapy plus an anti- EGFR MoAb in patients with RAS WT mCRC. RAVELLO was a phase III, international, double-blind, placebocontrolled, academic trial. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and toxicity. Regorafenib or placebo were administered daily for 3 weeks of 4-week cycle until disease progression or unacceptable toxicity, up to 24 months. Results The study was stopped prematurely due to slow accrual and lack of funding after the randomisation of 21 patients: 11 in the regorafenib arm and 10 in the placebo arm. The small sample size precludes any statistical analysis. Toxicity was acceptable and consistent with the known regorafenib safety profile. Median PFS was similar in the two arms. However, a subgroup of patients treated with regorafenib experienced a remarkably long PFS. Three patients were progression free at 9 months in the regorafenib arm versus one patient in the placebo arm, whereas at 12 months two regorafenib-treated patients were still progression free versus none in the placebo arm. Conclusion RAVELLO trial demonstrated that growing financial and bureaucratic hurdles affect the feasibility of independent academic research. Although stopped prematurely and within the limited sample size, RAVELLO suggests that regorafenib has not a major activity in maintenance setting after upfront chemotherapy and anti-EGFR MoAb. However, a subgroup of patients experienced a remarkable long PFS, indicating that a better refinement of the patient population would help to identify subjects that might benefit from a regorafenib personalised approach in the switch maintenance settin

Management of patients with early-stage colon cancer: guidelines of the Italian Medical Oncology Association

About 75% of colorectal cancers are diagnosed as early stage, in which radical surgery is achievable. In the last decade, in Italy, the overall incidence of colorectal cancer has remained stable, while mortality gradually decreased, which is attributable to early diagnosis and improved medical, surgical and locoregional treatments. The Italian Medical Oncology Association formulated guidelines to manage early-stage colon cancer, including screening, diagnosis, treatment and follow-up, which we herein present

Valutazione del comfort del paziente e della funzionalità di un sistema totalmente impiantabile venoso posizionato in vena safena

Background: When venous system of superior vena cava is not useful or when chest wall is not utilizable to place a reservoir, saphenous vein can be utilized for totally implantable venous access device (TIVAD) placement. Aim of this work is to establish the best location of the reservoir for the function and the comfort of the patient. Patients and methods: All the patients submitted to TIVAD placement from January 1995 to October 2004 at the Department of Surgical Science, Organs Transplantantions and Advanced Technologies of University of Catania have been considered to the present study. Age, sex, kind of disease, surgical procedure, early and late complications, function of the system and comfort to the patients in relation to the different site of reservoir placement have been studied. Results: 447 TIVAD have been implanted in 258 males and 189 females aged from 31 to 79 years in the period considered for the study. Solid tumors represent the majority of the indications and all the TIVAD have been implanted by surgical cutdown to avoid all the early complications related to the percutaneous approach. Two patients received their TIVAD using saphenous vein by surgical cutdown, and no early complications have been recorded. The reservoirs have been placed respectively: in the chest wall in the first patient; and in the anterior wall of the abdomen, close to the anterosuperior iliac crest, firstly and later in the anterolateral face of the thigh in the second one. The first patient had non complications instead the second one referred discomfort with both reservoir locations. Conclusions: For the comfort of the patient related to the reservoir position in case of saphenous vein utilization chest wall should represent the best studies are required to validate the appropriate reservoir location

Importanza del nursing nella prevenzione delle complicanze dei sistemi totalmente impiantabili

to riportato il caso clinico di un paziente sottoposto a chemioterapia in cui si è verificata una complicanza da non corret - to nursing. Il paziente, a cui era stato inserito un sistema totalmente ed impiantabile venoso ed era sottoposto a terapia antiblastica, durante un ciclo di chemioterapia ha accusato la sintomatologia dovuta allo stravaso di farmaci antiblastici. I sintomi sono regrediti rapidamente interrompendo l’infusione e non si è verificata alcuna complicanza a distanza. Gli Autori, dopo aver illustrato gli effetti collaterali dei vari far - maci antiblastici e le relative terapie, concludono puntualizzando la necessita di un corretto nursing al fine di prevenire le complicanze e di non aggravare quindi lo stato psicologico del paziente affetto da cancro

Merkel cell carcinoma responsive to Etoposide: a case report and brief literature review

Merkel cell carcinoma (MCC), first described in 1972, is an aggressive primary cutaneous carcinoma able to incorporate both epithelial and neuroendocrine features. MCC mainly appears in individuals in their eighth decade and it is related to a high mortality rate. The etiology of this rare disease is not well-understood but ultraviolet radiation exposure, immune suppression, and aging have a consistent role in its pathogenesis. Usually, clinical lesions appear as asymptomatic coloured dermal nodules. The tumour can involve lymph nodes but further evaluation with imaging is recommended. The common approach for localized disease is surgical. This work reports a case of an 86-year-old man with locally advanced MCC where, based on clinical experience, oral mono-chemotherapy with single-agent etoposide was chosen as first-line therapy. A complete objective response was achieved in 2 months

Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy

Novel targeted therapies for metastatic colorectal cancer are needed to personalize treatments by guiding specific biomarkers selected on the genetic profile of patients. RAS and BRAF inhibitors have been developed for patients who become unresponsive to standard therapies. Sotorasib and adagrasib showed promising results in phase I/II basket trial and a phase III trial was planned with a combination of these RAS inhibitors and anti-EGFR monoclonal antibodies. Encorafenib and binimetinib were administered in phase II clinical trials for BRAF mutated patients. Pembrolizumab is now recommended in patients exhibiting microsatellite instability. Larotrectinib and entrectinib showed a fast and durable response with few and reversible adverse events in cases with NTRK fusions. Trastuzumab and trastuzumab deruxtecan exhibited promising and durable activity in HER-2-positive patients. In this review, the reasons for an extension of the molecular profile of patients were assessed and placed in the context of the advancements in the understanding of genetics. We highlight the differential effect of new targeted therapies through an ever-deeper characterization of tumor tissue. An overview of ongoing clinical trials is also provided

Is G8 geriatric assessment tool useful in managing elderly patients with metastatic pancreatic carcinoma?

Aim: This paper aims to analyze the usefulness of the G8 geriatric oncology questionnaire in patients with advanced/metastatic pancreatic adenocarcinoma (aPAC) and its possible association with different clinical outcomes. Methods: Patients age > 70 years were screened with the G8 tool and treated with intravenous nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 for 3 consecutive weeks followed by one-week rest as prescribed after clinical evaluation by treating oncologists. Patient’s charts were evaluated for type and severity of toxicity, 2 cycle rate of completion, discontinuation rate, delays, dose reductions, and other outcomes response rates, progression-free, and overall survival. Sensitivity, specificity, and possible correlations were analyzed. Results: Sensitivity and specificity of the G8 score for severe toxicity were respectively 55.9% and 50%. No association between all types of severe grade 3-4 toxicity, delays, or dose reductions, and the G8 score was present (p= 0.622). ORR was 32.5% with no complete responses. Median PFS and OS were 4.5 months and 8.1 months, respectively. Correlation between G8 score and PFS was not statistically significant (p=0.0652). Correlation between G8 score and OS was statistically significant (p=0.0251). Although median survival of G8 fit patients was superior to that of G8 vulnerable patients (6.5 versus 4 months), the difference was not statistically different (p= 0.1975). Conclusion: Clinical results in terms of response rate, survival outcomes, and side-effects were in the range reported by others. However, the G8 questionnaire is not a reliable diagnostic tool to predict the risk of severe toxicity, and clinical outcomes in older patients with aPAC

Efficacy of A Fluoropyrimidine plus Mitomycin C in Pretreated Patients with Metastatic Colorectal Cancer Eligible for Regorafenib: A Retrospective Study

Objective: In the placebo-controlled CORRECT study, individuals with metastatic colorectal cancer (mCRC) receiving Regorafenib (RGR) achieved significant benefits in both median overall survival (OS: 6.4 months) and progression-free survival (PFS 1.9 months). Patients included in the study had previously failed all standard therapies, which must have included Fluoropyrimidines (FPDs), Oxaliplatin, Irinotecan, Bevacizumab, and Cetuximab or Panitumumab for K-RAS wild-type subjects. FPDs plus Mitomycin C (MMC) represent one of the few treatment options for mCRC patients currently eligible for RGR. We wanted to investigate the therapeutic benefit of this pharmacological association in the same clinical setting defined for RGR. Methods: We retrospectively evaluated the records of mCRC patients followed in our Institutions that would have fulfilled inclusion/exclusion criteria for the CORRECT trial and received instead the combination of FPDs and MMC. We therefore collected data from 87 patients: 61 fulfilled the criteria required for this analysis. Results: Median OS was 9.3 months (95% CI 9.0–15.4), with a median PFS of 3.3 months (95% CI 2.9–3.8). One third of the patients (29.5%) achieved disease control. No significant differences in OS and PFS were found between K-RAS WT and K-RAS mutant individuals. Likewise, Performance Status (PS) and the primary site of disease were not associated with differences in response rates. Conclusions: These results suggest the need for a prospective study assessing RGR cost-effectiveness compared to FPDs plus MMC for mCRC patients that progress after standard treatments