Use of nivolumab in elderly patients with advanced squamous non-small-cell lung cancer: results from the Italian cohort of an expanded access programme.

Aim: This analysis evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in elderly patients with stage IIIB or IV squamous non-small-cell lung cancer (NSCLC) enrolled in the expanded access programme (EAP) in Italy.

Methods: Nivolumab was available on physician request. Safety data included adverse events (AEs).

Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy.

Background: Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care.

Methods: Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity.

Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors.

The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48).

Adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of spermatic cord leiomyosarcoma.

Background: The aim of this report is related to adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of the spermatic cord leiomyosarcoma. Primary paratesticular tumors are rare, only accounting for 7% to 10% of all intrascrotal tumors. In adults, more than 75% of these lesions arise from the spermatic cord, 20% being leiomyosarcoma.

Medical oncologist's commitment in end-of-life care of cancer patients.

Objective: Cancer patients and family members can feel abandoned by their oncologist at the transition to end-of-life (eoL) care. In this study, we evaluated the level of satisfaction of family caregivers when the oncology team assisted the patient until death.

Methods: Two oncology units were reorganized to ensure continuity of care; oncologists trained in palliative care medicine assisted patients until death.

Impact of use of oral anticancer drugs on activity of Italian oncology practices: results of a survey conducted by the Italian Society of Medical Oncology (AIOM).

Aims And Background: In recent years, the number of oral anticancer drugs used in clinical practice has rapidly increased. The Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of the use of oral anticancer drugs on the daily activity of Italian oncology practices.

Methods And Study Design: A survey questionnaire was distributed to the coordinators of the regional sections of AIOM.

A phase II study of modified FOLFOX as first-line chemotherapy for metastatic gastric cancer in elderly patients with associated diseases.

Background: Elderly patients are generally underrepresented in the study populations of combination chemotherapy trials. This study evaluates the efficacy and safety of a modified FOLFOX regimen in elderly patients with metastatic gastric cancer and presenting associated disease(s).

Methods: A total of 43 patients aged ≥70 years received oxaliplatin 85 mg/m(2) together with 6S-leucovorin 200 mg/m(2) on day 1, followed by a 46-h infusion of 5-fluorouracil 2,400 mg/m(2), every 2 weeks.

Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.

Background: Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment.

Methods: We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and corresponding metastases and global outcome in K-RAS wild type patients receiving irinotecan-cetuximab.

Disparity in the "time to patient access" to new anti-cancer drugs in Italian regions. Results of a survey conducted by the Italian Society of Medical Oncology (AIOM).

Aims And Background: In 2009, the Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of regional pharmaceutical formularies on the disparity of access to eight new drugs among cancer patients treated in Italian regions. The survey documented some regional restrictions for some anti-cancer drugs. In the study, we analyzed the "time to patient access" to new anti-cancer drugs in Italian regions.

Differences in the availability of new anti-cancer drugs for Italian patients treated in different regions. Results of analysis conducted by the Italian Society Of Medical Oncology (AIOM).

Aims And Background: Italy is divided into 20 regions. As a consequence of local autonomy, following marketing authorization by the Italian Medicines Agency, each drug for hospital use is not immediately available, because its approval needs to undergo further steps that can be different among regions. The Italian Society of Medical Oncology conducted the present study to describe the impact of the existence of sub-national pharmaceutical formularies on the disparity of access to new anti-cancer drugs among patients treated in different Italian regions.

Triple-negative breast cancer: current state of the art.

Aims And Background: Triple-negative breast cancer, defined by a lack of expression of estrogen, progesterone and HER-2 receptors, accounts for 15% of all types of breast cancer. The subtype mainly includes a molecularly distinct subgroup, the basal-like subtype (accounting for 75% of all cases). We attempt to define triple-negative breast cancer and compare it with basal-like disease, review the molecular, pathologic and clinical features of triple-negative disease, provide an overview of a retrospective subset analysis of clinical trials, and outline ongoing therapeutic trials and possible paths for future research.

The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan and cetuximab.

Preclinical data suggested that, in the presence of human epidermal growth factor receptor (HER)-3-altered activation, colorectal cancer cells may escape anti-epidermal growth factor receptor (EGFR)-mediated cell death. HER-3 overexpression may then represent a key factor for resistance to anti-EGFR antibodies in colorectal cancer. The aim of our analysis was to investigate a possible correlation between HER-3 expression and clinical outcome in wild-type K-RAS advanced colorectal cancer patients receiving cetuximab and irinotecan.

Insulin-like growth factor 1 expression correlates with clinical outcome in K-RAS wild type colorectal cancer patients treated with cetuximab and irinotecan.

Seventy to 40% of K-RAS wild type colorectal tumors does not seem to benefit from treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies. Recent data suggested that in presence of IGF-1 system, altered activation colorectal cancer cells may escape anti-EGFR mediated cell death. The interaction between IGF-1 expression and K-RAS mutational analysis was tested to verify the ability of IGF-1 to identify a subgroup of patients more likely to benefit from EGFR-targeted antibodies treatment.

Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer.

Purpose: Regulation of epidermal growth factor receptor (EGFR) signaling pathways may play a relevant role in determining the activity of cetuximab therapy in patients with metastatic colorectal cancer (MCRC). We investigated possible associations between genetic variants and clinical outcomes of MCRC patients treated with cetuximab-irinotecan salvage therapy.

Patients And Methods: Patients who underwent cetuximab-irinotecan salvage therapy after disease progression during or after first-line bolus/infusional fluorouracil, leucovorin, and oxaliplatin chemotherapy and a second-line irinotecan-based regimen were considered eligible for analysis of polymorphisms with putative influence on cetuximab-related pathways.

Polymorphisms in genes involved in DNA repair and metabolism of xenobiotics in individual susceptibility to sporadic diffuse gastric cancer.

Background: Gastric cancer is the second highest cause of cancer mortality in the world, despite declining rates of incidence in many industrialized countries. We carried out a case-control study to evaluate whether polymorphisms of DNA repair and glutathione S-transferase (GST) genes modulate the risk of developing diffuse gastric cancer.

Methods: ERCC1 118 T/C, XRCC1 399 G/A, XPD 312 G/A, XPD 751 A/C, XRCC3 241 C/T, MS 919 A/G, GSTP1 105 A/G, GSTM1-null/positive and GSTT1-null/positive genotypes were obtained for a series of 126 Helicobacter pylori-negative diffuse gastric cancer patients and 144 Helicobacter pylori-negative controls sampled from the population of Marche, an area with high gastric cancer risk in central Italy.

Informal caregiving burden in advanced non-small cell lung cancer: the HABIT study.

Introduction: This study's aim was to assess economic data regarding the home assistance burden for advanced non-small cell lung cancer (NSCLC) patients in Italy.

Patients And Methods: One hundred four NSCLC patients in second-line chemotherapy (2LC) or in supportive therapy (ST) were enrolled in 18 Italian oncology departments and were observed for 3 months. The main caregiver's workload was assessed monthly by a task scale; other caregivers' activities were also registered.

Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy.

Purpose: The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy.

Materials And Methods: Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion.

Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy.

Purpose: To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer (AGC).

Patients And Methods: Peripheral blood samples from 175 prospectively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13 polymorphisms in nine genes (TS, MTHFR, XPD, ERCC1, XRCC1, XRCC3, GSTPI, GSTTI, GSTMI). Genotypes were correlated to response and survival.

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population.

We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) and gastric cancer susceptibility in at-risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T genotyping.

Prognostic role of thymidylate synthase polymorphisms in gastric cancer patients treated with surgery and adjuvant chemotherapy.

Purpose: To investigate the prognostic role of thymidylate synthase (TS) polymorphisms in gastric cancer patients treated with radical surgery and fluorouracil-based adjuvant chemotherapy.

Experimental Design: Ninety gastric cancer cases were identified among 187 patients previously enrolled in prospective case-control studies for disease susceptibility. Patients were genotyped for a G/C nucleotide change within a triple 28 bp variable number of tandem repeat sequence in the TS 5'-untranslated region (5'-UTR) and a 6 bp deletion in the TS 3'-untranslated region (3'-UTR).

Paclitaxel and mitoxantrone in metastatic breast cancer: a phase II trial of the Italian Oncology Group for Cancer Research.

Background: In a previous dose-finding trial, in previously treated patients with metastatic breast cancer (MBC), we showed that the combination of Mitoxantrone (M) and Paclitaxel (P) may be an interesting (response rate: 69%) and well-tolerated regimen. On the basis of these results, our group started a new trial in chemotherapy-naive patients with MBC.

Patients And Method: Forty-six women entered in this trial, and all patients were evaluated for response and toxicity.