G Tonini

Publications (150)364.54 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: 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: 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: Adjuvant colon cancer chemotherapy: where we are and where we'll go.

  L Lombardi, F Morelli, S Cinieri, D Santini, N Silvestris, N Fazio, L Orlando, G Tonini, G Colucci, E Maiello
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  ABSTRACT: Many patients with early-stage colon cancer are cured with surgery alone, even if the standard of care remains an uniform approach to adjuvant chemotherapy based primarily on tumour stage. Consequently, it is important to individualize decision-making in this subset of patients with the aim to identify potential prognostic and predictive markers in colon cancer. While 5-fluorouracil, leucovorin, and oxaliplatin are widely known as gold treatment in the post-operative of stage III, well-validated molecular markers might help define which patients with stage II disease are likely to benefit from adjuvant therapy as well. Herein we review the use of adjuvant chemotherapy in colon cancer and analyzed the date on the clinical development of molecular markers to individualize another therapeutic approach in colon cancer.
  Cancer treatment reviews 11/2010; 36 Suppl 3:S34-41. · 5.30 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
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  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
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  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: 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
• Article: Hormone-Biological Therapy in Breast Cancer: Preclinical Evidence,Clinical Studies and Future Directions

  G. Schiavon, G. Tonini
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  ABSTRACT: Background: The development of resistance to endocrine agents is a major issue in the treatment of ER-positive breast cancer patients. Evidence of cross-talk among signaling pathways and recent advances in understanding biology of this neoplasm have led to the new concept of hormone-biological therapy. Aims: The main aim of this review was to comprehensively examine ongoing and concluded clinical trials about endocrine agents used in combination with biological drugs. The second aim was to provide up-to-date knowledge of preclinical studies in this flourishing field, considering several in vitro and in vivo models, by focusing on the main signaling pathways involved in breast tumorigenesis. Materials and Methods: We performed a literature search for papers published in MEDLINE database until January 2009. We selected the most significant data presented as abstract or poster during the relevant international meetings for breast cancer (ASCO, ESMO and San Antonio Breast Cancer Symposium). Moreover, we systematically reviewed a publicly available registry of federally and privately supported clinical trials conducted in the United States and around the world to provide updated information about concluded trials and ongoing trials not yet published. Results/Conclusion: Hormone-biological therapy is a relatively new option in the treatment of breast cancer with and some combinations seemingly effective in certain settings. Numerous trials are ongoing and they will help to better clarify the role of different combined therapies. In parallel, cancer biology has a central role in providing a deeper understanding of this heterogeneous disease where preclinical studies will be necessary to test new compounds and strategies.
  Current Cancer Drug Targets 01/2010; 10(1):3-18. · 4.33 Impact Factor
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  Available from: John Mackey

  Article: Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes.

  G Perrone, S Morini, D Santini, C Rabitti, B Vincenzi, R Alloni, A Antinori, P Magistrelli, R Lai, C Cass, J R Mackey, R Coppola, G Tonini, A Onetti Muda
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  ABSTRACT: The human equilibrative nucleoside transporter 1 (hENT1) is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively). Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036), while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.
  European journal of histochemistry: EJH 01/2010; 54(3):e38. · 1.69 Impact Factor
• Article: New perspectives: role of sunitinib in breast cancer.

  M E Fratto, M Imperatori, B Vincenzi, F Tomao, D Santini, G Tonini
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  ABSTRACT: Sunitinib malate (SU11248) is a multitarget oral tyrosine kinase receptor (RTKs) inhibitor which was approved by FDA in renal cells carcinoma (RCC) and imatinib-resistant or imatinib-intollerant gastrointestinal stromal tumour (GIST). Sunitinib is able to inhibit RTKs such as receptors for platelet-derived growth factor (PDGF-R alpha and beta) and for vascular endothelial growth factor (VEGFRs). It is able to inhibit KIT receptor, colony stimulating factor type 1 receptor (CSF- 1R), glial cell line neutrophic factor receptor (RET), fms-like tyrosine kinase receptor-3 (FLT-3 or CD135), signal transducer and activator of transcription 3 (STAT3) and AKT (protein kinase B) in tumour cells. Many sunitinib targets play important roles in growth and survival of human breast cancer (BC). The "rationale" of sunitinib in BC (with or without others antiagiogenetic therapy) is its ability to block simultaneously intracellular portion of RTKs inhibiting many downstream signals. We overviewed the most relevant studies concerning sunitinib in metastatic BC.
  La Clinica terapeutica 01/2010; 161(5):475-82. · 0.27 Impact Factor
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  Available from: Francesco Pantano

  Article: Potential role of everolimus in inducing cholestasis.

  F Pantano, D Santini, F Guida, B Vincenzi, G Tonini
  Annals of Oncology 12/2009; 21(2):433. · 6.43 Impact Factor
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  Available from: oxfordjournals.org

  Article: Longitudinal evaluation of vitamin D plasma levels during anthracycline- and docetaxel-based adjuvant chemotherapy in early-stage breast cancer patients.

  D Santini, S Galluzzo, B Vincenzi, A Zoccoli, E Ferraro, C Lippi, V Altomare, G Tonini, F Bertoldo
  Annals of Oncology 11/2009; 21(1):185-6. · 6.43 Impact Factor
• Article: Cutting the limits of aminobisphosphonates: new strategies for the potentiation of their anti-tumour effects.

  M Marra, A Abbruzzese, R Addeo, S Del Prete, P Tassone, G Tonini, P Tagliaferri, D Santini, M Caraglia
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  ABSTRACT: Therapy with aminobisphosphonate (N-BPs), and zoledronic acid (ZOL) especially, has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that N-BPs exert their direct or indirect anti-tumour effects on cancer growth factor release, cancer cell adhesion, invasion and viability, cancer angiogenesis and cancer cell apoptosis. Here, we will discuss the molecular mechanisms of the antitumour effects induced by ZOL. Despite their well-established in vitro anti-tumour effects N-BPs have not clear in vivo anti-tumour activity in humans. The bases of these discrepancies will be discussed in the text with a special focus on the pharmacokinetic limits of N-BPs. Moreover, the following molecular and pharmacological strategies in order to overcome N-BPs limitations will be described: i) development of pharmacological combinations with other biological agents; ii) finding of new molecular targets of N-BPs; iii) development of new pharmacological formulations of N-BPs. Finally, a new scenario of integrated bio-medicine and pharmacology will be depicted in order to drive the optimization of anti-cancer activity of N-BPs.
  Current cancer drug targets 11/2009; 9(7):791-800. · 5.13 Impact Factor