B Vincenzi

Publications (87)335.6 Total impact

• Article: 'All action no talk': the role of HER2/neu in adjuvant therapy choice for gastric cancer.

  D Santini, B Vincenzi, F Pantano, G Schiavon, G Tonini
  Annals of Oncology 05/2013; · 6.43 Impact Factor
• Article: Prevention of delayed emesis induced by moderately emetogenic chemotherapy in patients with acute emesis

  D. Santini, B. Vincenzi, C. Fossati, R. M. D’Angelillo, G. Patti, V. Bianco, G. Avvisati, G. Tonini
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  ABSTRACT: The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients. During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy). In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as ≤ 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects. The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial.
  Medical Oncology 04/2012; 18(2):131-135. · 2.14 Impact Factor
• Article: Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?

  D Santini, B Vincenzi, R Addeo, C Garufi, G Masi, M Scartozzi, A Mancuso, A M Frezza, O Venditti, M Imperatori, G Schiavon, G Bronte, G Cicero, F Recine, E Maiello, S Cascinu, A Russo, A Falcone, G Tonini
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  ABSTRACT: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options.
  Annals of Oncology 03/2012; 23(9):2313-8. · 6.43 Impact Factor
• Article: Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis.

  P Gazzaniga, A Gradilone, E de Berardinis, G M Busetto, C Raimondi, O Gandini, C Nicolazzo, A Petracca, B Vincenzi, A Farcomeni, V Gentile, E Cortesi, L Frati
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  ABSTRACT: Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.
  Annals of Oncology 02/2012; 23(9):2352-6. · 6.43 Impact Factor
• Article: Natural history of bone metastasis in colorectal cancer: final results of a large Italian bone metastases study.

  D Santini, M Tampellini, B Vincenzi, T Ibrahim, C Ortega, V Virzi, N Silvestris, R Berardi, C Masini, N Calipari, [......], C Caroti, L Salvatore, A Falcone, P Giordani, R Addeo, M Aglietta, S Cascinu, S Barni, E Maiello, G Tonini
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  ABSTRACT: Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P=0.009) and produced a trend toward improved overall survival versus no zoledronic acid. This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting.
  Annals of Oncology 01/2012; 23(8):2072-7. · 6.43 Impact Factor
• Article: Serum VEGF levels as predictive marker of bisphosphonate-related osteonecrosis of the jaw

  B. Vincenzi, A. Napolitano, A. Zoccoli, M. Iuliani, F. Pantano, N. Papapietro, V. Denaro, D. Santini, G. Tonini
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  ABSTRACT: ABSTRACT: Recent studies have been reported that angiogenesis suppression may play a role in developing bisphosphonate-related osteonecrosis of the jaw (B-ONJ). According to these evidence we evaluated the role of VEGF as predictive marker of B-ONJ onset. Of the 81 patients, 6 developed B-ONJ following bisphosphonate treatment. These patients showed a strongest decrease in VEGF circulating levels at day 7 and at day 21 after the first administration. These data demonstrated for the first time that the anti-angiogenic properties of bisphosphonates are directly linked to B-ONJ pathogenesis and serum VEGF levels could represent an effective early predictive marker.
  J Hematol Oncol. 01/2012; 5(1):56.
• Article: Prognosis of mucinous histology for patients with radically resected stage II and III colon cancer.

  V Catalano, F Loupakis, F Graziano, R Bisonni, U Torresi, B Vincenzi, D Mari, P Giordani, P Alessandroni, L Salvatore, L Fornaro, D Santini, A M Baldelli, D Rossi, L Giustini, R R Silva, A Falcone, S D'Emidio, M Rocchi, S Luzi Fedeli
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  ABSTRACT: Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.
  Annals of Oncology 04/2011; 23(1):135-41. · 6.43 Impact Factor
• Article: Evaluation of Cisplatin as an electrochemotherapy agent for the treatment of incompletely excised mast cell tumors in dogs.

  E P Spugnini, B Vincenzi, G Citro, I Dotsinsky, T Mudrov, A Baldi
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  ABSTRACT: Electrochemotherapy (ECT) couples the administration of anticancer drugs with the delivery of electric pulses that increase the drug uptake through the cell membranes, resulting in an improved efficacy. To evaluate the tolerability and efficacy of cisplatin (CDDP) as an ECT agent to prevent recurrence of incompletely resected mast cell tumors (MCTs). Thirty-seven dogs. Prospective study recruiting dogs with incompletely excised MCTs as confirmed by surgeon and pathology reports. After debulking, the tumor bed and margins were infiltrated with CDDP, and then exposed to trains of biphasic electrical pulses under sedation. Five minutes after the injection of the chemotherapy agent, sequences of 8 biphasic pulses lasting 50 + 50 μs each, were delivered in bursts of 1,300 V/cm for sclerosed and of 800 V/cm for exposed lesions, with caliper or needle array electrodes, respectively. A second session was performed 1 or 2 weeks later based on clinical considerations. The treatment was well tolerated with minimal adverse effects. Twenty-nine dogs had no evidence of recurrence over the 6-year study period, 6 had tumor recurrence, 1 died of multiple cutaneous MCTs, and 1 died of unrelated causes. The estimated median time to recurrence was 1,200 days. Recurrence was not observed among the long-term (> 1 year) treated dogs. ECT with CDDP appears effective in the treatment of incompletely resected MCT in dogs and could be a useful addition to the current options based on its low cost, limited toxicity, and ease of administration.
  Journal of Veterinary Internal Medicine 03/2011; 25(2):407-11. · 1.99 Impact Factor
• Source

  Available from: Paola Stiuso

  Article: Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR.

  M Caraglia, G Giuberti, M Marra, R Addeo, L Montella, M Murolo, P Sperlongano, B Vincenzi, S Naviglio, S Del Prete, A Abbruzzese, P Stiuso
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  ABSTRACT: We reported a relevant activity of the combination between sorafenib and octreotide long-acting release (LAR) in advanced hepatocellular carcinoma (HCC) patients. In this work, we have studied if oxidative stress in both serum and peripheral blood mononuclear cells (PBMC) and pERK activation status in PBMC could be predictive of response. In the 20 responsive patients, the decrease of reactive oxygen species levels was already detectable after 10 days (T10) from the beginning of sorafenib administration, and this effect was enhanced by the combined treatment with sorafenib+octreotide LAR (T21). This effect correlated with the modulation of superoxide dismutase (SOD) activity (physiological scavenger of O(2-)) and of serum nitric oxide (NO) levels. Sorafenib alone induced an increase of about 40% of NO levels and of about two-fold of SOD activity in responsive patients, and both effects were significantly potentiated by the combined treatment. We found a gradual reduction of Erk1/2 activity, as evaluated by cytofluorimetric analysis, in 15 responsive patients reaching about 50% maximal decrease at T21. On the other hand, in 17 resistant patients, Erk1/2 activity was about 80% increased at T21. The determination of both the oxidative stress status and pERK activity in PBMC has high value in the prediction of response to sorafenib+octreotide therapy in HCC patients.
  Cell Death & Disease 01/2011; 2:e150. · 5.33 Impact Factor
• Article: Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC)

  D. Santini, G. Schiavon, B. Vincenzi, C. E. Cass, E. Vasile, A. D. Manazza, V. Catalano, G. G. Baldi, R. Lai, S. Rizzo, A. Giacobino, L. Chiusa, M. Caraglia, A. Russo, J. Mackey, A. Falcone, G. Tonini
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  ABSTRACT: BACKGROUND AND AIM: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. MATERIALS AND METHODS: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. RESULTS: Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128). CONCLUSIONS: Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC.
  Current cancer drug targets. 01/2011; 11(1):123-9.
• Article: Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization.

  A Gradilone, G Naso, C Raimondi, E Cortesi, O Gandini, B Vincenzi, R Saltarelli, E Chiapparino, F Spremberg, M Cristofanilli, L Frati, A M Aglianò, P Gazzaniga
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  ABSTRACT: the expression of ATP-binding cassette transporters on circulating tumor cells (CTCs) is predictive of response to chemotherapy in cancer patients. We tested the hypothesis that drug-resistant CTCs might have predictive value in metastatic breast cancer (MBC) and possibly retain stem-like properties. CTCs obtained from 42 MBC patients were evaluated for multidrug-resistance-related proteins (MRPs), aldehyde dehydrogenase 1 (ALDH1), estrogen receptor α (ERα) and human epidermal growth factor receptor 2 (HER2/neu). Primary objective was to evaluate the prognostic and predictive value of CTCs profile. Secondary end points were the level of concordance in ERα and HER2/neu status between primary tumors and CTCs and the correlation in CTCs between ALDH1, drug resistance profile and number of MRPs. A difference in progression-free survival (PFS) was found between CTCs-positive and CTCs-negative patients. PFS was shorter in patients with a 'drug resistance' CTCs profile and in patients whose CTCs expressed two or more MRPs. No correlation was found between tumor characteristics and ALDH1. ALDH1 correlated to negative ERα and positive HER2/neu status in CTCs. The correlation between the number of MRPs expressed in CTCs and ALDH1 was statistically significant. in MBC, the presence of CTCs expressing MRPs and ALDH1 is predictive of response to chemotherapy.
  Annals of Oncology 01/2011; 22(1):86-92. · 6.43 Impact Factor
• Article: CD133 and ABCB5 as stem cell markers on sentinel lymph node from melanoma patients.

  P Gazzaniga, E Cigna, V Panasiti, V Devirgiliis, U Bottoni, B Vincenzi, C Nicolazzo, A Petracca, A Gradilone
  European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 12/2010; 36(12):1211-4. · 2.56 Impact Factor
• Source

  Available from: Antonio Russo

  Article: New molecular targets in bone metastases.

  D Santini, S Galluzzo, A Zoccoli, F Pantano, M E Fratto, B Vincenzi, L Lombardi, C Gucciardino, N Silvestris, E Riva, S Rizzo, A Russo, E Maiello, G Colucci, G Tonini
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  ABSTRACT: Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future. Targeting the bone by preventing skeletal related events (SREs) and bone metastases has major clinical impact in improving survival in bone metastatic patients and in preventing disease relapse in adjuvant setting.
  Cancer treatment reviews 11/2010; 36 Suppl 3:S6-S10. · 5.30 Impact Factor
• Source

  Available from: Andrea Napolitano

  Article: Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients.

  B Vincenzi, S Galluzzo, D Santini, L Rocci, F Loupakis, P Correale, R Addeo, A Zoccoli, A Napolitano, F Graziano, A Ruzzo, A Falcone, G Francini, G Dicuonzo, G Tonini
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  ABSTRACT: KRAS wild-type mutational status is necessary but not sufficient to get benefit from epidermal growth factor receptor inhibition. Predictive markers are currently being evaluated. In this study, we investigated early hypomagnesemia as a predictor of efficacy and outcome in terms of time to progression (TtP) and overall survival (OS) in a cohort of patients affected by advanced colorectal adenocarcinoma KRAS wild-type cetuximab-treated. One hundred and forty-three patients affected by stage IV colorectal adenocarcinoma KRAS wild type receiving cetuximab + irinotecan (CTX+IRI) as third-line anticancer treatment and resistant to oxaliplatin- and irinotecan-based chemotherapy were retrospectively included. Magnesium plasma levels were measured before the first day and 7, 14, 21 and 28 days after CTX+IRI infusion. The median magnesium basal value showed a statistically significant decrease after the start of CTX+IRI treatment (at 28 days, P < 0.0001). Patients with an early decrease of magnesium levels >50% compared with the basal level had a higher tumor response rate (55.8% versus 16.7%, P < 0.0001), a longer TtP (6.3 versus 3.6, P < 0.0001) and a longer median OS (11.0 versus 8.1, P = 0.002). We have shown that early hypomagnesemia could be a predictor of efficacy and outcome in those patients. Magnesium circulating level is an easy and inexpensive biomarker to routinely be detected in patients treated with cetuximab.
  Annals of Oncology 11/2010; 22(5):1141-6. · 6.43 Impact Factor
• Source

  Available from: PubMed Central

  Article: Cetuximab in small bowel adenocarcinoma: a new friend?

  D Santini, M E Fratto, C Spoto, A Russo, S Galluzzo, A Zoccoli, B Vincenzi, G Tonini
  British Journal of Cancer 10/2010; 103(8):1305; author reply 1306. · 5.04 Impact Factor
• Article: Role of KRAS let-7 LCS6 SNP in metastatic colorectal cancer patients.

  A Ruzzo, E Canestrari, N Galluccio, D Santini, B Vincenzi, G Tonini, M Magnani, F Graziano
  Annals of Oncology 10/2010; 22(1):234-5. · 6.43 Impact Factor
• Source

  Available from: Nadia Galluccio

  Article: High concordance of BRAF status between primary colorectal tumours and related metastatic sites: implications for clinical practice.

  D Santini, C Spoto, F Loupakis, B Vincenzi, N Silvestris, C Cremolini, E Canestrari, F Graziano, N Galluccio, L Salvatore, M Caraglia, F A Zito, G Colucci, A Falcone, G Tonini, A Ruzzo
  Annals of Oncology 07/2010; 21(7):1565. · 6.43 Impact Factor
• Article: Urinary complications from breast cancer metastasis: case report and review of the literature.

  E Vulcano, M Montesano, C Battista, R Carino, G Perrone, B Vincenzi, V Altomare
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  ABSTRACT: Breast cancer is the most prevalent malignant disease among women, with the exception of non-melanoma skin cancers. Malignant breast tumours metastasise to lungs, bone, liver, lymph nodes and skin, but the literature also reports few cases of unusual metastases such as to the bladder. We present the case of a 57-year-old woman affected by lobular invasive breast cancer and complaining of high urinary frequency with nicturia. To date this is the seventh reported case of isolated metastatis of breast carcinoma to the bladder.
  Il Giornale di chirurgia 05/2010; 31(5):243-5.
• Article: Chemotherapy in biliary tract cancer.

  G Tonini, M E Frato, B Vincenzi, D Santini
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  ABSTRACT: BACKGROUND: Biliary Tract Cancer is a rare and aggressive tumor characterized by unresponsiveness to chemotherapy and radiotherapy in the vast majority of cases. Surgery offers the only possibility of a cure, though post-operative disease recurrence is common. Only few randomized trials with few patients have been conducted to in this setting of patients and standard chemotherapy has not been established yet. RESULTS AND CONCLUSIONS: This article summarizes the most important clinical trials regarding chemotherapy for biliary tract cancer and the first evidences regarding the adjuvant treatment. Moreover the clinical trials evaluating targeted therapy will be described, especially those assessing the role of anti-EGFR and antiangiogenic agents.
  European review for medical and pharmacological sciences 04/2010; 14(4):371-4. · 1.04 Impact Factor
• Article: Genetic modulation of the Let-7 microRNA binding to KRAS 3'-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan.

  F Graziano, E Canestrari, F Loupakis, A Ruzzo, N Galluccio, D Santini, M Rocchi, B Vincenzi, L Salvatore, C Cremolini, C Spoto, V Catalano, S D'Emidio, P Giordani, G Tonini, A Falcone, M Magnani
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  ABSTRACT: There is increasing evidence that the Let-7 microRNA (miRNA) exerts an effect as a tumor suppressor by targeting the KRAS mRNA. The Let-7 complementary site (LCS6) T>G variant in the KRAS 3'-untranslated region weakens Let-7 binding. We analyzed whether the LCS6 variant may be clinically relevant to patients with metastatic colorectal cancer (MCRC) treated with anti-epidermal growth factor receptor (EGFR) therapy. LCS6 genotypes and KRAS/BRAF mutations were determined in the tumor DNA of 134 patients with MCRC who underwent salvage cetuximab-irinotecan therapy. There were 34 G-allele (T/G+G/G) carriers (25%) and 100 T/T genotype carriers (75%). G-allele carriers were significantly more frequent in the KRAS mutation group than in patients with KRAS wild type (P=0.004). In the 121 patients without BRAF V600E mutation, overall survival (OS) and progression-free survival (PFS) times were compared between carriers of the LCS6 G-allele genotypes and carriers of the wild-type T/T genotype. LCS6 G-allele carriers showed worse OS (P=0.001) and PFS (P=0.004) than T/T genotype carriers (confirmed in the multivariate model including the KRAS status). In the exploratory analysis of the 55 unresponsive patients with KRAS mutation, LCS6 G-allele carriers showed adverse OS and PFS times. These findings deserve additional investigations as they may open novel perspectives for the treatment of patients with MCRC.
  The Pharmacogenomics Journal 02/2010; 10(5):458-64. · 4.54 Impact Factor