Guido Bocci

University of Pisa | UNIPI · Department of Translational Research on New Technologies in Medicine and Surgery

Metronomic, or continuous low-dose, chemotherapy produces antitumor effects through multiple mechanisms. These include inhibition of angiogenesis and activation of the immune system. At AACR 2017 we presented a small, proof-of-concept, multiplex analysis of 14 cytokines specifically chosen by their association with activation of the immune system....

Purpose of Review This review describes the most relevant studies found in the scientific literature regarding metronomic chemotherapy (MCT) in the geriatric oncology population to support its use as a feasible treatment of care in the frail elderly patients. Recent Findings Recent years have seen a reevaluation of cancer chemotherapeutic drugs an...

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium...

In the original publication [...]

In this article, we reviewed the possible mechanisms linking the clonal hematopoiesis of indeterminate potential (CHIP) to chronic myeloproliferative neoplasms (MPNs), autoimmune diseases (ADs), and cardiovascular diseases (CADs). CHIP is characterized by the presence of clonal mutations with an allelic frequency >2% in the peripheral blood without...

Objectives Opioid use disorder (OUD) and cancer gained attention as co-occurring diseases in the last 2 decades due to the possible relationship between opioid prescriptions for cancer pain and the risk of developing substance use disorder in cancer patients. However, little is known about patients previously diagnosed with OUD who develop cancer a...

Aims: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated r...

TTuberous sclerosis (TS) is a rare autosomal dominant genetic multisystem disease caused by mutations in either the TSC1 or TSC2 gene and results in the growth of non-cancerous masses in several organs. Diffuse large B-cell lymphoma (DLBCL) is the predominant non-Hodgkin lymphoma in adolescents and young adults. Metronomic chemotherapy (mCHEMO) ca...

Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabolic interactions among different drugs. For these...

Despite advances in the therapy of Central Nervous System (CNS) malignancies, treatment of glioblastoma (GB) poses significant challenges due to GB resistance and high recurrence rates following post-operative radio-chemotherapy. The majority of prognostic and predictive GB biomarkers are currently developed using tumor samples obtained through sur...

Metastatic breast cancer is a major cause of death for women in the US, and breast cancers that metastasize to the brain have a particularly poor prognosis. To treat brain metastases of Her-2 positive breast cancers a number of Her-2 targeting drugs are now clinically available, including lapatinib, neratinib and tucatinib, among others. However, i...

Beyond its use as an antiepileptic drug, over time valproate has been increasingly used for several other therapeutic applications. Among these, the antineoplastic effects of valproate have been assessed in several in vitro and in vivo preclinical studies, suggesting that this agent significantly inhibits cancer cell proliferation by modulating mul...

The upfront treatment of very elderly and frail patients with diffuse large B-cell lymphoma (DLBCL) is still a matter of debate. Herein, we report results of the metronomic all-oral DEVEC [prednisolone/deltacortene®, vinorelbine (VNR), etoposide (ETO), cyclophosphamide] combined with i.v. rituximab (R). This schedule was administered as a first lin...

Metronomic chemotherapy (MC) is the frequent, regular administration of drug doses designed to maintain a low, but active, range of concentrations of chemotherapeutic drugs, during prolonged periods of time without inducing excessive toxicities. To date, more than 400,000 children and adolescents under the age of 20 are diagnosed with cancer, per y...

Background: Although liver biopsy remains the gold standard for the diagnosis and the monitoring of liver disease, non-invasive biomarkers have been recently suggested to predict liver disease severity, progression, and response to therapy. We investigated multiple tissue and circulating markers of angiogenesis in predicting the severity of biopsy...

The angiogenesis process was described in its basic concepts in the works of the Scottish surgeon John Hunter and terminologically assessed in the early twentieth century. An aberrant angiogenesis is a prerequisite for cancer cells in solid tumors to grow and metastasize. The sprouting of new blood vessels is one of the major characteristics of can...

Ramucirumab plus paclitaxel is considered the standard of care in the second-line treatment of gastric carcinoma (GC). The aim of this study was to evaluate plasma vascular endothelial growth factor-A (VEGF-A), VEGF-D, and circulating soluble VEGF receptor-2 (sVEGFR-2) as possible markers of resistance or response to ramucirumab administered with p...

A series of novel 3,4‐dihydrobenzo[4,5]imidazo[1,2‐a][1,3,5]triazine (BIT) derivatives were designed and synthesized. In vitro antiproliferative activity was detected toward two human colorectal adenocarcinoma cell lines (CaCo‐2 and HT‐29) and one human dermal microvascular endothelial cell line (HMVEC‐d). The most active compounds, namely 2‐4 and...

Background. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods. We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated...

Glioblastoma multiforme (GBM) is an aggressive brain tumor, often occurring with seizures managed with antiepileptic drugs, such as levetiracetam (LEV). This study is aimed at associating progression-free survival (PFS) and overall survival (OS) of GBM patients with LEV plasma concentration, MGMT promoter methylation, and sex In this retrospective,...

To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1, and TSP-1 SNPs and their role on progression-free survival (PFS) in metastatic breast cancer (MBC) patients treated with bevacizumab plus first-line paclitaxel or with paclitaxel alone. Analyses were performed on germline DNA, and SNPs were investigated by real...

Therapeutic drug monitoring (TDM) is an effective tool used to improve the pharmacological treatment in clinical practice, especially to detect subtherapeutic drug plasma concentration (Cp) in order to consider a change of dosage during treatment and reach its putative therapeutic range. In this study, we report the Cp values of lithium and valproi...

Metronomic chemotherapy (MC) is the frequent, regular administration of chemotherapeutic drugs that maintain a low, prolonged and active range of plasma concentrations with a favorable toxicity profile. MC regimens were developed to optimize the antitumor efficacy of agents that could impact multiple targets, including the tumor vasculature, regula...

Breast cancer is one of the most important causes of premature mortality among women and it is one of the most frequently diagnosed tumours worldwide. For this reason, routine screening for prevention and early diagnosis is important for the quality of life of patients. Breast cancer cells can enter blood and lymphatic capillaries, then metastasizi...

Seizures are relatively common in cancer patients, and co-administration of chemotherapeutic and antiepileptic drugs (AEDs) is highly probable and necessary in many cases. Nonetheless, clinically relevant interactions between chemotherapeutic drugs and AEDs are rarely summarized and pharmacologically described. These interactions can cause insuffic...

Novel drugs are rapidly moving forward the treatment-paradigm of non-Hodgkin-lymphomas (NHLs). Notwithstanding, especially in aggressive subtypes, chemotherapy remains the pillar of treatment. Indeed, the combination of highly effective Maximum-Tolerated-Dose Chemotherapy (MTD-CHEMO) + “novel drugs”, has so far, fallen short from expectations, ofte...

Non-alcoholic fatty liver disease is the most common liver disorder worldwide, and its progressive form non-alcoholic steatohepatitis (NASH) is a growing cause of liver cirrhosis and hepatocellular carcinoma (HCC). Lifestyle changes, which are capable of improving the prognosis, are hard to achieve, whereas a pharmacologic therapy able to combine e...

This study reports the results of a monocentric prospective analysis conducted with the aim of evaluating the impact of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms (SNP) on patients with high-grade glioma treated with concomitant radio-chemotherapy. From October 2010 to August 20...

A Correction to this paper has been published: https://doi.org/10.1007/s10637-021-01097-3

Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor, often occurring with seizures. The current standard of care for cancer patients who present seizures includes the use of antiepileptic drugs (AEDs), such as levetiracetam (LEV). Some preclinical studies have shown that LEV may act as histone deacetylases inhibitor (HDACi)...

This review addresses, in a critical historical perspective, the link between seizures and endocranic neoplasms. Folkloric descriptions of epilepsy can be found in writings from ancient cultures. Hippocrates first provided a medical interpretation. In 1770, Tissot published Traité de l'épilepsie, a milestone in epileptology, whereas the 19th centur...

Metronomic chemotherapy has shown promising antitumor activity in a number of malignancies. We previously reported a phase II clinical trial of metronomic UFT (a 5-fluorouracil prodrug; 100 mg/twice per day p.o.) and cyclophosphamide (CTX; 500 mg/m² i.v. bolus on day 1 and then 50 mg/day p.o.) plus celecoxib (200 mg/twice a day p.o.) in 38 patients...

PurposePeripheral T cell lymphomas (PTCLs) have an overall poor prognosis. Indeed, registry data in elderly patients show that the median progression-free survival (mPFS) following first- and second-line therapies are only 6.7 and 3.1 months, respectively. The aim of the study is to show the activity of metronomic chemotherapy, a regular administra...

The aim of our study was to investigate the effects of metronomic vinorelbine (mVNR) in a tumor model of Lewis Lung (LL) cancer in immunocompetent C57BL/6 mice, looking at the plasma levels of interleukin-2 (IL-2) and interleukin-8 (IL-8). mVNR caused a concentration-dependent antiproliferative effect in vitro on LL/2 cells. The in vivo experiment...

Among the main challenges for the treatment of breast cancers is disease spread which is often coupled with resistance to chemotherapy. Furthermore, patients with late stage breast cancer go through first- and second-line therapies before they are candidates for new and/or experimental therapies. At such late stages, tumors that might have responde...

Breast cancer is one of the most malignant diseases, associated with high rate mortality. In this chapter a particular attention is paid on cardiovascular and central nervous system toxicity induced by chemotherapeutic agents used for both primary and metastatic treatment of this life-threatening pathology. With respect to traditional drugs, includ...

Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, and novel combined therapies are urgently needed to prolong patient survival. No data are currently available on the preclinical activity of the combination of linifanib, a CSF-1R inhibitor, and irinotecan in ATC. The aim of the study was to evaluate the in vitro and in...

Stimulation of opioid receptors is widely used for relieving cancer pain in patients with advanced cancer. The expression of tissue opioid receptors varies depending on the types of cancer and it is regulated by several factors. This review provides a focused overview of the current evidence for the role of opioid receptors in modulating cancer pro...

Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to vinorelbine, lenvatinib, as well as to concomitant combinations. ABCB1, ABCG2 and CSF-1 mRNA expression was evaluated by real time PCR. The relative levels of pospho Akt were invest...

The first description of epileptic seizures due to brain tumours occurred in 19th century. Nevertheless, after over one hundred years, scientific literature is still lacking on how epilepsy and its treatment can affect tumour burden, progression and clinical outcomes. In patients with brain tumours, epilepsy dramatically impacts their quality of li...

Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, and novel therapies are urgently needed to prolong patient survival and improve clinical outcomes. Very few scientific reviews have examined the literature on combination therapies with the goal of describing the available preclinical and clinical data and suggesting fut...

The aim of this study was to investigate possible synergistic effects in vitro of trifluridine/tipiracil (TAS-102) and 5-fluoruracil (5-FU) on fluoropyrimidine-sensitive colon cancer cell lines of different mutational status in order to build a rational basis for the future use of this combination therapy in adjuvant settings or as a first-line tre...

Cytotoxic immunosuppressive agents have a long-standing important role in pharmacological IMMUNOSUPPRESSION. Azathioprine was among the first immunosuppressive drugs used in organ transplantation. A further development in this field was landmarked by the introduction of ALKYLATING AGENTS (i.e. cyclophosphamide) and ANTIMETABOLITES (i.e. methotrexat...

Poster# P316, Oncological Pharmacology I [Chairperson: Lucia Morbidelli (Siena)]

Poster# P319, Oncological Pharmacology I [Chairperson: Lucia Morbidelli (Siena)]

The purpose of this study was to examine pazopanib/topotecan combination activity vs. pazopanib monotherapy on anaplastic thyroid cancer (ATC) cells. Proliferation analyses were performed on ATC cell lines administered for 72 h with pazopanib and topotecan alone and to their simultaneous combination. Pazopanib and topotecan produced a strong synerg...

Context Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis. Objective The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF rece...

Melanoma is the most serious form of skin cancer but its medication is still far from being safe and thoroughly effective. The search of novel therapeutic approaches represents therefore a health emergency to push through eagerly. In this study, we describe a novel class of dual c-Kit/Aur inhibitors, characterized by a 1,2,4-triazole core and devel...

Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as f...

The aim of the study was to evaluate the effects and the related pharmacological mechanisms of switched schedules of antiangiogenic and chemotherapeutic drugs beyond progression after a first-line treatment in a colorectal cancer preclinical model. In vivo studies were performed in nude mice subcutaneously transplanted with colon cancer cells. The...

Introduction Metronomic chemotherapy (mCHT) is a treatment regimen in which drugs are administered frequently or continuously and that maintains low, prolonged, and pharmacologically active plasma concentrations of drugs to avoid toxicity associated with traditional chemotherapy regimens, while achieving tumor response. Despite the increasing use o...

Background: Endocrine Therapy (ET) is a mainstay in Hormone Receptor-positive Breast Cancer treatment. The ability to counter estrogenic signaling in mammary tissue has made Selective Estrogen Receptor Modulators, Aromatase Inhibitors and the Selective Estrogen Receptor Degrader fulvestrant essential therapies in both early and late stage settings,...

Aim To construct classification scores based on a combination of cancer patient plasma biomarker levels, for predicting progression-free survival. Methods The approach is based on the optimization of the biomarker cut-off values, which maximize the statistical differences between the groups with values lower or larger than the cut-offs, respective...

The aim of the present study was to assess the pharmacokinetics (PK) of metronomic capecitabine and its metabolites in a population of refractory metastatic colorectal cancer (mCRC) patients. Thirty-four patients (M/F, 22/12) with a diagnosis of mCRC received capecitabine 800 mg p.o. twice a day and cyclophosphamide 50 mg/day p.o. Blood samples wer...

Recent advances for the treatment of late stage colon cancer include a metronomic capecitabine plus bevacizumab maintenance regimen as reported for the CAIRO3 phase 3 clinical trial (Simkens et al, Lancet: 2015; 385: 1843-52) . We previously reported a phase 2 trial evaluating metronomic cyclophosphamide (CTX) plus UFT (a 5-fluorouracil prodrug) an...

Currently, no description of melanocortin receptor-4 (MC4R) expression or activity is available in human cancer cells, including glioblastoma (GBM). The aim of this study is to evaluate the presence of MC4Rs in GBM cells and the selective inhibition of their activity through the MC4R antagonist ML00253764 alone and in association with temozolomide...

Tumor dormancy is the ability of cancer cells to survive in a non-proliferating state. This condition can depend on three main mechanisms: cell cycle arrest (quiescence or cell dormancy), immunosurveillance (immunologic dormancy), or lack of functional blood vessels (angiogenic dormancy). In particular, under angiogenic dormancy, cancer cell prolif...

Objectives: Bevacizumab is an anti-vascular endothelial growth factor antibody used in the treatment of recurrent glioblastoma (GBM). Despite the large number of studies carried out in patients with recurrent GBM, little is known about the administration of this angiogenesis inhibitor after the failure of the second-line chemotherapy. Materials a...

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free surviva...

Metronomic vinorelbine (mVNR) has been described primarily as an antiangiogenic therapy, and no direct effects of mVNR on Non Small Cell Lung Cancer (NSCLC) cells has yet been demonstrated. The aims of this study were i) to establish the direct activity of mVNR on NSCLC cells either EGFR wt or EGFRL858R/T790M, and ii) to quantify the synergism of t...

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the hum...

The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated...

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognos...

Purpose: The reporting of suspected adverse drug reactions (ADRs) is starting to become routine to nurses. The aim of this review is to underline the role of clinical and community health nurses in pharmacovigilance and to promote their effective participation in ADR reporting in different countries and for patients of different ages. Methods: T...