The role of polymorphisms occurring in BRCA1/2 genes in determining ovarian cancer risk.

e17551 Background: Ovarian cancer (OC) is the 10th tumor occurring in women, it accounts for 30% of all malignant tumor affecting female genital tract in Italy. There are several factors that contribute to OC development; in 15-25% of cases family history of breast and ovarian cancer represent the main risk factor. It is well known that pathogenic variants (PVs) occurring in BRCA1/2 genes strongly increase the risk of developing OC, ranging from 50% in BRCA1 PVs carriers to 30% in BRCA2 PVs carriers. Recently genetic polymorphism has been shown to increase cancer risk, consequently polymorphisms in BRCA1/2 genes could represent low penetrance susceptibility alleles and contribute to determ…

Antiangiogenic effects, safety and feasibility of two different capecitabine/Oxaliplatin-based schedules in elderly colorectal cancer patients

Efficacy of weekly low-dose chemotherapy in elderly women with advanced ovarian cancer: is there an antiangiogenic effect?

13133 Background: In elderly patients decreased functionality of multiple organ systems may affect pharmacokinetics and pharmacodynamics of drugs. For this reason elderly cancer patients experience enhanced susceptibility to common chemotherapy-related adverse events. A way to prevent these effects could be metronomic chemotherapy, which is a variation of dose-dense therapy, with a cumulative dose significantly lower than maximum tolerated dose. Methods: 27 advanced ovarian cancer patients, median age 67 (range 60–86), received low dose weekly continuous chemotherapy until disease progression. All patients were treated with CBDCA AUC 2 mg/ml/min and Docetaxel 35 mg/sqm (adjusted according …

Advanced breast cancer at presentation (ABC-p) in octogenarian women (OW): Specific elderly-devoted risk tests(SEDRT) (CARG+CRASH) as new tools to prevent serious/irreversible adverse reactions (AR) in frail patients.

e12510 Background: Due to current lengthening of average lifespan and progressive increase of malignant tumors in mankind, more new strategies must be constantly sought especially for thirdage neoplasms. Nevertheless because severe toxicity developed in the majority of frail patients, administration of therapy may cause high risk of life-threatening AIM: We have considered in this paper ABC in frail patients like OW. Purpose of the study is preliminary detection of the overall toxicity (OTox) through the possible use of specifics tests adopted specially in frail patients such as OW, to ensure greater control in drugs administration with good effectiveness. AIM: We have considered in this p…

An all-oral combination regimen of vinorelbine and capecitabine for elderly patients with metastatic breast cancer

How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.

e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF an…

Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy

Forty patients with chemotherapy-related diarrhea were randomized to receive (i) octreotide 0.5 mg three times per day s.c. or (ii) loperamide 4 mg three times per day p.o. until complete remission of diarrhea was achieved. In the octreotide group 80% of patients showed complete resolution of loose bowel movements within 4 days of therapy, while in the loperamide group this goal was obtained in only 30% of cases (p < 0.001). If after 4 days no benefit was seen, patients were considered to have failed antidiarrheal therapy. Failure was recorded in only one case (5%) treated with s.c. octreotide and in five patients (25%) who received loperamide. The mean duration of antidiarrheal therapy nec…

Cell-free DNA and exoDNA analysis in metastatic colorectal cancer patients (mCRC).

e16093 Background: Liquid biopsy is a growing field in translational cancer research. Two of the most studied liquid biopsy biomarkers are cell-free DNA (cfDNA) and exosomes, nano-sized vesicles that transport protein and nucleic acids including DNA (exoDNA). Therefore, both cfDNA and exoDNA are potentially useful to investigate the molecular landscape of tumor with a minimally invasive approach. Here we investigate the prognostic and predictive role of both cfDNA and exoDNA in mCRC using Next Generation Sequencing (NGS) analysis. Methods: From July 2017 to September 2018, samples of 40 mCRC patients were collected at the Medical Oncology of the AOUP Paolo Giaccone of Palermo. Blood sample…

1. Uncommon Unresectable Advanced Ulcerative Scirrhous Carcinoma of the Nipple Destroying skin, Chest, Muscles and Ribs. Complete Remission (CR) After Epidoxorubicin (EDOX) + Gemcitabine (GEM) Weekly Administration - A Case Report

Eribulin (E) and capecitabine (C), a combined treatment schedule in elderly metastatic breast cancer (EMBC): Efficacy and safety evaluation (E&amp;S).

e20513 Background: E mesylate, a nontaxane microtubule dynamics inhibitor, was approved in the U.S in 2010 for the treatment of MBC who have previously received at least 2 MBC chemo regimens, inclu...

VEGF and Chromogranin A (CgA): Possible new predictive factors in management of advanced prostatic cancer (APC) in elderly patients

Safety and efficacy of two different schedules of capecitabine combined with oxaliplatin in the treatment of colon cancer in the elderly

Comparison between gemcitabine-based combination (G) and single-agent chemotherapy (S) for elderly patients (EP) with advanced non-small cell lung cancer (NSCLC): A literature-based meta-analysis

19586 Background: It was estimated that a quarter of all patients who have a diagnosis of NSCLC worldwide are more than 70 years old. This meta-analysis tries to shed light on the controversial results of phase III trials evaluating in NSCLC EP doublets against third generation S. Methods: We performed a literature search using MEDLINE and Cochrane Library. We selected only clinical trials responding to the question of our meta-analysis. Outcomes recorded were 1-year survival rate (1-y SR), overall response rate (ORR) and haematological toxicity (HT). Fixed-effects and random-effects models were used to calculate pooled odds ratios (OR). An OR greater than 1 indicates that doublet is more …

Antiangiogenic scheduling of lower dose chemotherapy in elderly patients with advanced colorectal cancer

Metronomic therapy irinotecan (IRI) capecitabine (CAP) plus bevacizumab (BEV) in treatment of advanced colorectal cancer (ACRC) in very elderly people.

Background: ACRC is one of most common neoplastic disease in very old pts. The administration of oral fluoropyrimidine (capecitabine-CAP) in a standard schedule of 1,200 mg/sqm twice a day for 14 d shows similar effects to 5-FU continuous infusion (C.I.). Furthermore, CAP- IRI showed super -additive antitumor activity. Recently many study show the safety and efficacy of a "flat dose" administration of CAP particularly in the treatment of elderly people with cancer. Also, the efficacy of BEV is well demonstrated in CRC pts. Aim of the study is to evaluate impact of bevacizumab (BEV) in combination with IRI and XEL in ACRC very old patients. Methods: 42 (20 f-22 m) elderly patients with advan…

Sorafenib (SFB) treated elderly patients (E) with hepatocellular carcinoma (HCC): Chromogranine A (CGA) plus vascular endothelial growth factor (VEGF) as predicting factors (PF) of treatment outcome.

e14676 Background: HCC accounts for approximately 90% of all primary liver cancers, and is the fifth most common cancer in the world and prognosis is so far very poor,particularly in E patients.Between all tentative of treatment till know SFB seems to be the most promising drug in patients with advanced or metastatic HCC.Aim of the study is to investigate if SFB is efficient and safe also in E HCC patients despite the comorbidities and other problems. Objectives: To investigate if CgA and VEGF work as predicting factors of Sorafenib treatment outcomes. Methods: 51 patients, mean age 68,9 (65-85) with HCC were enrolled . Serum CgA, VEGF and αFP were evaluated at baseline and after end of tr…

Cancer chemotherapy in the older cancer patient.

This article reviews the principles of systemic cancer treatment in older individuals. These include: assessment of physiologic age with a comprehensive geriatric assessment (CGA), adjustment of chemotherapy doses to the patient's renal function, and prevention of myelotoxicity with hemopoietic growth factors. Other complications that become more common with age include mucositis, peripheral neuropathy and cardiomyopathy. Two chronic complications of chemotherapy become more common with age, including myelodysplasia and chronic cardiomyopathy. The goal of systemic cancer treatment in the older person should include prolongation of active life-expectancy and compression of morbidity in addit…

Impact of the new 5-HT3 receptor antagonist palonosetron (P) in chemotherapy-induced nausea and vomiting (CINV) control in elderly advanced breast cancer (EABC) patients: Comparison with the classic antiemetic agent ondansetron (O).

Treating cancer in older and oldest old patients.

The so-called “silver tsunami” is a metaphor that the individuals 65 and older represent the most rapidly growing segment of the Western world population. Aging is an ongoing process that leads to the loss of functional reserve of multiple organ systems, increased susceptibility to stress, it is associated with increased prevalence of chronic disease, and functional dependence. Determined by a combination of genetic and environmental factors, this process is highly individualized and poorly reflected in chronologic age. The heterogeneity and the complexity of the older old population represent the main challenge to the treatment of cancer in those patients. We should discern "fit" elderly i…

Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?

Abstract: Objective: miRNAs are attractive molecules for cancer treatment, including colon rectal cancer (CRC). We investigate on the molecular mechanism by which miR-182 could regulate thrombospondin-1 (TSP-1) expression, a protein down-regulated in CRC and inversely correlated with tumor vascularity and metastasis. Background: MicroRNAs are small non-coding RNAs that regulate the expression of different genes, involved in cancer progression, angiogenesis and metastasis. miR-182, over-expressed in colorectal cancer (CRC), has like predictive target thrombospondin-1 (TSP-1), a protein inversely correlated with tumor vascularity and metastasis that results downregulated in different types of…

Temozolomide (TMZ) in radio-chemotherapy combined schedule for treatment of newly-diagnosed high-grade gliomas (HGG)

1578 Background: Temozolomide (TMZ) is an oral alkylating agent known to cross the blood-brain barrier with efficacy against HGG and a favourable safety profile compared to conventional chemotherap...

Metronomic (M), capecitabine (C), and oxaliplatin (O) plus bevacizumab (B) as treatment of advanced colorectal cancer (ACRC) in very elderly people (M-COB): Efficacy and safety (E&S) evaluation—A 2-year monitoring

Background: A limit to delivery of cytotoxic chemotherapy in elderly people with cancer, is severe toxicity as principal side effect of treatment. We designed in 2009 a treatment schedule to evaluate E&S of combination of three drugs O, C plus B in ACRC very old patients in a metronomic mode (M-COB) Methods: 75 (37 f -38 m) very elderly patients with advanced colorectal cancer (median age:76; range: 70-82) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to all pts to assess eligibility for chemotherapy. Treatment schedule was: O (65 mg/m2) + B (7.5 mg/Kg) on day 1 (O doses was adjusted by Kintzel-Dorr formula). C (fixed dose of 1,000 mg bid) was delivered from day 2 to…

Capecitabine (XEL) + Oxaliplatin (OX) in elderly people (EP) with Colorectal Cancer (CRC): Comparison of safety (S) and feasibility (F) of two different schedules. Preliminary findings

Cancer in the older person.

Cancer in the older person is an increasingly common problem, due to the progressive prolongation of the life-expectancy of the Western population. This article reviews the mechanisms associating aging and cancer, age-related changes in cancer biology, assessment of the older person to estimate life-expectancy, treatment tolerance, and medical and social conditions that may interfere with cancer treatment, effectiveness of cancer prevention and cancer treatment in older individuals. A comprehensive geriatric assessment (CGA) is commonly used to predict life-expectancy and functional reserve and to unearth conditions that may jeopardize cancer prevention and treatment. In the interest of cos…

Oncogeriatry: Communication, sharing, coordination of an emerging reality. The IIIrd Official Meeting of the AIOM Working Group on Oncogeriatry

The clinical management of the oncological elderly patient represents one of the most important challenges for today's oncology and, above all, for the future. The number of elderly patients with neoplastic pathologies is destined to increase proportionally to the duration of life and therefore a correct management of their conditions becomes an element of priority from the scientific and economic point of view. Close relationships and collaborations between Oncologist and Geriatrics are definitely desirable to be able to guarantee the best way for a good treatment (specific and of support) of these elderly patients. The components of the AIOM Working Group on Oncogeriatry have gathered the…

Combination of eribulin (E) and capecitabine (C) in elderly metastatic breast cancer (MBC): Update of a new option suitable in older elderly.

9540 Background: E mesylate, a nontaxane microtubule dynamics inhibitor is widely prescribed for MBC pts pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&...

Myelotoxicity from cytostatic treatment, an important risk factor in the management of neoplasias in the elderly

Myelotoxicity is the most common complication of cancer chemotherapy. A brief review of hematopoiesis is necessary to understand the mechanisms of myelotoxicity and the treatment strategies that may minimize this complication in elderly patients. From this review of hematopoiesis and age, we may draw three conclusions: aging is associated with a progressive reduction in hematopoietic reserve; by itself, the decline in hematopoietic reserve does not produce abnormalities of the circulating blood, these may occur as a consequence of hematopoietic stress; hematopoietic growth factors are effective in promoting granulopoiesis and erythropoiesis in older individuals. Alternative strategies inclu…

Oral Chemotherapy for the Older Patient with Cancer

Oral chemotherapy presents a number of theoretical advantages in older cancer patients, including convenience of administration and dosage flexibility. Of the oral fluorinated pyrimidines, capecitabine is the most promising, because it minimizes the exposure of normal tissue to the active drug and substantially reduces the risk of mucositis, that is particularly common and severe in the aged. Despite promising initial results, oral etoposide does not offer any special advantage over the intravenous formulation for older patients, while oral temozolomide may have a role in the palliation of malignant melanoma and primary and secondary brain tumors. Of the experimental agents, oral platinum (…

Sorafenib (SFB) low dose in octogenarians with advanced or inoperable (a/i) HCC: Toxicity and efficacy evaluation.

e20719 Background: HCC accounts for approximately 90% of all primary liver cancers, and is the fifth most common cancer in the world. So far prognosis of AHCC is very poor, particularly if consider very elderly pts. Treatment with SFB at standard dose may results in untolerable toxicity especially in very old people with HCC Cancer Aim of the study is to investigate if SFB at reduced dose is efficient and tolerable in octogenarian people with HCC. Methods: 30 patients,16 male and 14 female with AHCC histologically proven were enrolled; mean age was 79. Main Inclusion Criteria: Child-Pugh A or B; adequate liver, hematological, and renal function; informed writed consent acquired. Comprehens…

Reticulocytes can represent an early indicator of erythropoietic response to Darbepoetin alfa in the anemia by chemotherapy

Background: Darbepoetin is a new drug active in anemia from chemotherapy and 2-to 3- times longer serum half life then recombinant-human Epo (rHuEPO). Reticulocytes can constitute an useful parameter to check the medullar reserve and give an indication of the erythropoietic answer. Methods: 42 patients in chemotherapy were randomised in 3 groups: the first two reported severe asthenia and have been deal respective with (I) darbepoetin 2.25μg/kg once weekly or (II) rHuEPO 150 U/Kg three times weekly; the third group (III), used like control, did not report relevant asthenic symptoms. The study evaluated time zero, after 4 and 8 weeks hemoglobin, reticulocyte count,serum ferritin, transferrin…

Effects of erybuline/capecitabine (EC) treatment in very elderly women (VEW) with MBC.

e12508 Background: Eribuline mesylate, is widely prescribed for MBC pts alone or in combination with Capecitabine in patients pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&amp;T). Elderly Patients (EP) develop rapid and sometimes fatal toxicity during treatments due to pharmacokinetic features of these drugs.A combination schedule (E+C) to evaluate its suitability for VEW with MBC patients ,was used in this study. Methods: Treatment plan: E 0.96 mg/sqm IV on d1 every 21d - C 900 mg/sqm bid d1-14 every 28d (Dose-adjustement if necessary was according to Kintzel-Dorr’s formula for elderly), schedule administration continued until progression or i…

A phase II study of oxaliplatin (O) and gemcitabine (G) first line chemotherapy in patients with advanced biliary tract cancers

Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients (pts) present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, but single or combination-drug schedules have demonstrated poor response rates with a median survival less than 6 months. Recently O and G have showed an interesting activity as single agents in this group of pts. Methods: We carried out a multicenter phase II study to evaluate the efficacy and safety of combined O and G in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included O 100 mg/m2 on day 1 and G 1000 mg/m2 on days 1 and 8, every 21 days. I…

Assessment and treatment of elderly people with cancer: Italian (AIOM–SIGG) onco-geriatric survey results

Supportive care of the older cancer patient

Aging is associated with decreased functional reserve of multiple organ systems and with changes in the pharmacokinetics and pharmacodinamics of drugs. Older individuals express enhanced susceptibility to the complications of cytotoxic chemotherapy, especially to myleotoxicity, mucositis, cardiotoxicity and neurotoxicity. The management of older individuals with chemotherapy involves then prevention of these complications. General precautions include proper patient selection, based on the comprehensive geriatric assessment (CGA), dose adjustment for agents that are renally excreted to the patient creatinine clearance and maintenance of hemoglobin levelsor =12 g/dl. Filgrastim and pegfilgras…

VEGF levels could affect outcomes in elderly breast cancer women

Neoadjuvant oxaliplatin (OXA), raltitrexed (TOM), 5-fluorouracil (FU) and folinic acid (FA) + radiotherapy followed by optimal surgery in locally advanced rectal cancer (LARC)

9624 Background: Preoperative chemoradiation in LARC may produce downstaging and downsizing of the tumor, increases the change of better local control and, in selected cases, sphincter sparing proc...

VEGF values as a predictive factor of treatment efficiency in elderly women with advanced breast cancer

Gemcitabine-based doublets versus single-agent therapy for elderly patients with advanced nonsmall cell lung cancer: a Literature-based Meta-analysis.

BACKGROUND: Although platinum-based combinations are considered the best option of care for patients with advanced nonsmall cell lung cancer (NSCLC), single-agent therapy is the preferred treatment for older patients. Since the late 1990s, various combinations of third-generation agents (gemcitabine [G], vinorelbine, docetaxel, and paclitaxel) have been tested, yielding contradictory results. The authors of this report performed a literature-based meta-analysis to assess the efficacy and tolerability of G-based doublets compared with single-agent chemotherapy for elderly patients with NSCLC. METHODS: Data from all published, randomized, phase 3 trials that compared a G-based doublet with a …

FULVESTRANT AND CAPECITABINE IN ELDERLY ADVANCED BREAST CANCER PATIENTS: THE PROPOSAL FOR AN EFFECTIVE AND SAFE COMBINED TREATMENT SCHEDULE.

Founder mutations in BRCA1 and BRCA2 genes

BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive f…

Combined treatment with fulvestrant plus capecitabine in elderly advanced breast cancer (EABC): Three-year evaluation of efficacy and safety

Background: EABC affects about 45% of all advanced breast cancers and actually treatments are always more toxic than effectiveness. Fulvestrant (F), the first of a new class of pure estrogen receptor antagonists, competitively binds to estrogen receptors on tumors and inhibit tumor growth. Capecitabine (C) is converted to 5-FU by thymidine phosphorylase and shows good efficacy and low toxicity as single agent in EABC. Since elderly cancer pts are extremely susceptible in development of rapid toxicity during treatment with cytotoxic drugs, we design this chemo-hormone combined schedule to evaluate if F + C could increase efficacy profile in EABC women. Methods: 41 EABC pts (mean age 72; rang…

Weekly cisplatin-epirubicin-paclitaxel vs. dose-dense cisplatin-epirubicin-vinorelbine in locally advanced breast cancer: Interim analysis of the SICOG 0302 phase III trial.

Non-Pegylated Liposomal Doxorubicin/Cyclophosphamide-based schedule As Antiangiogenic Treatment In Elderly Women With Advanced Breast Cancer

SAFETY AND EFFICACY OF INHALED IL-2 THERAPY IN PRE-TREATED BREAST CANCER ELDERLY PATIENTS WITH PULMONARY METASTASES.

Tailored vinorelbine-capecitabine treatment in elderly metastatic breast cancer patients. A SICOG phase II study

Capecitabine (XEL) and oxaliplatin (OX) in combination with bevacizumab (BEV) in the management of elderly patients with advanced colorectal cancer (ACRC): Preliminary outcomes on safety and efficacy.

Background: Older individuals always experience enhanced susceptibility to the side effects of cytotoxic chemotherapy. The aim of the study was to evaluate impact of BEV in combination with OX and XEL in ACRC elderly patients. Methods: 56 (29 male, 27 female) elderly patients with ACRC (median age: 71; range: 66-80) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. The dose of IRI and XEL was adjusted according to Kintzel-Dorr formula. Primary endpoint: clinical response rates (RR) according to WHO criteria. Secondary endpoints: toxicity profile using NCI-CTC v2.0 and quality of life (QoL) score measured through EORTC QLQ-C30 quest…

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasm…

Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression

Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular transduction of the signals. In colorectal cancer nm23 protein expression seems related to the progression of the disease. By immunohistochemistry we have studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected by colorectal cancer at initial stage. In 12 cases it resulted elevated and in four the disease recurred. The overexpression was not correlated with other prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at initial stage could be considered at risk for disease recurrence and included in a more frequent follow-up protocol.

Alla ricerca della sicurezza e della qualità: il modello di miglioramento dell'Oncologia Medica nel Policlinico Universitario di Palermo

[In search of safety and quality: the improvement model proposed by the Oncology Department of the Palermo University] Over the past 20 years the field of oncology has product therapeutic innovations that have radically changed the prognosis of the most prevalent malignancies, since introduction of so-called targeted molecular agents. As a result of these changes, also the management of cancer patients has become more complex requiring technologies and skills that involve many professionals (medical oncologists, biologists, molecular geneticists, surgeons, pathologists, radiologists, nurses and psychologists), each engaged in a different stage of the disease, with the common goal of ensurin…

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