Gina Turrisi

San Giuseppe Hospital, Ареццо, Tuscany, Italy

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Publications (20)39.13 Total impact

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    ABSTRACT: Diphtheria toxin (DT) has shown anticancer activity in both experimental models and humans but its adverse effects stopped further developments. Cross-reacting Material 197 (CRM197) is the product of a single missense mutation (Gly52 to Glu) within fragment A of DT. It has been shown to induce weak toxicity in some cell strains, but it shares immunological properties with native DT. CRM197 commonly acts as an immunological adjuvant, or as an inhibitor of heparin-binding epidermal growth factor. Recently, CRM197 was shown to have promising antitumor activity. To better-define this property, we planned a phase I-II study. Twenty-nine patients bearing advanced melanoma (18 cases), and other solid tumors (two ovarian cancer, two sarcoma, two gastrointestinal cancers, one urinary bladder carcinoma, one glioblastoma, one neuroblastoma, one ocular melanoma and one primitive neuroectodermal embriogenic tumor (PNET) were evaluated and 19 of them, sub-divided in cohorts, received the following levels of CRM197: Level 1, 0.3 mg; level 2, 1.0 mg; level 3, 2.5 mg; level 4, 3.5 mg; level 5, 5.0 mg; level 6, 7.5 mg. The drug was given once every two days for 4 times and then, after a 2-week rest period, once every 2 days for 4 times. CRM197 was administered subcutaneously in the abdominal wall. grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). Vomiting and abdominal pain, skin reaction tachycardia and hypotension appeared in two patients at level 5. At 7.5 mg, we observed a severe grade 3 reaction with hypotension, dyspnea and grade 4 myalgia. This was considered the dose-limiting toxicity. Eleven patients (seven with melanoma and four with other tumors) were treated to evaluate anticancer effects at the maximum tolerated dose (5 mg). Only one patient reported a minor response, lasting eight weeks. Ten patients reported progressive disease. CRM197, injected subcutaneously at 5 mg, elicited a generic inflammatory response causing toxicity, and did not exert a significant degree of antitumor activity in patients with advanced melanoma and solid tumour.
    In vivo (Athens, Greece) 03/2013; 27(2):197-202. · 1.15 Impact Factor
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    ABSTRACT: The simultaneous administration of irinotecan, 5-fluorouracil, folinic acid and oxaliplatin (FOLFOXIRI) has been compared with standard 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) in randomized trials in metastatic colorectal cancer patients. A superior efficacy of FOLFOXIRI has been reported by some authors, but others have failed to show any differences and do not recommend its use because of greater cost and toxicity. We performed a systematic review of the literature to analyse efficacy and toxicity of FOLFOXIRI. Odds ratios (OR) with 95% confidence intervals (CI) were used to analyse dichotomous variables. Hazard ratios (HR) for progression and death were combined with an inverse variance method based on logarithmic conversion. A fixed-effect model and Mantel-Haenszel's method were used. Heterogeneity was tested with Cochrane's Q test and I(2) test. A significant increase in response rate (OR 2.04; P < 0.01) was associated with treatment by FOLFOXIRI and a benefit was also shown by the HR for progression (HR 0.72; P < 0.01) and death (HR 0.71; P < 0.01). Analysis for toxicity found a significant increase associated with FOLFOXIRI except for anaemia, fatigue and febrile neutropenia. FOLFOXIRI confers significant benefit in progression-free survival, survival, response and R0 resection rates but is more toxic compared with FOLFIRI.
    Colorectal Disease 08/2011; 13(8):846-52. · 2.08 Impact Factor
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    ABSTRACT: Cisplatin has been largely used in the treatment of advanced, unresectable gastric cancer, mainly in combinations with fluoropyrimidines and anthracyclines. Oxaliplatin has been shown to be at least as effective as cisplatin for this disease, but with less toxicity and a better tolerability profile, especially for older patients. We performed a systematic review of the literature to address and quantify differences in the efficacy and the safety between oxaliplatin and cisplatin for the treatment of this disease. The literature was searched for randomized controlled trials (RCTs) comparing oxaliplatin to cisplatin. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze dichotomous variables. Hazard ratios (HRs) for progression and death were combined with an inverse variance method based on logarithmic conversion. A fixed effect model and Mantel-Haenszel's (M-H) method were used. Heterogeneity was tested with the Q test and the I (2) value. Sensitivity analyses were performed. Three RCTs were identified, involving a total of 1294 patients. Oxaliplatin significantly improved progression-free survival (HR = 0.88, p = 0.02) and overall survival (HR = 0.88, p = 0.04). Moreover, it was associated with less neutropenia (OR = 0.53, p < 0.01) and fewer thromboembolic events (OR = 0.42, p < 0.01), but it was also associated with increased neurotoxicity (OR = 6.91, p < 0.01). Our results support the existence of a small but significant survival benefit of oxaliplatin over cisplatin. Oxaliplatin is associated with less toxicity and better tolerability, especially in older patients and when used in two-drug, bi-weekly regimens.
    Gastric Cancer 02/2011; 14(1):50-5. · 3.99 Impact Factor
  • Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 02/2010; 68(5):1179-82. · 1.58 Impact Factor
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    ABSTRACT: Imatinib mesylate (IM) is a very important drug in the treatment of gastrointestinal stromal tumors (GISTs) and chronic myeloid leukaemia (CML). In large clinical trials conducted until now it demonstrated a good cardiac safety profile. However during the last years many reports indicated a possible IM-induced cardiotoxicity. Here we report a case of a patient with a GIST who developed a severe and irreversible cardiac failure during IM treatment. Interestingly, she suffered from chronic renal failure, a condition that does not contraindicate treatment. Our opinion is that IM-induced cardiotoxicity could be facilitated by the presence of relevant comorbidities such as pre-existing cardiovascular disease or renal failure, commonly present in daily practice but excluded from clinical trials. Phase IV studies are needed to address the question of the real incidence of IM-induced cardiotoxicity in the general population.
    International journal of cardiology 09/2009; 145(1):148-50. · 6.18 Impact Factor
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    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2008; 22(9):1781-2. · 10.16 Impact Factor
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    ABSTRACT: The extraordinary success of imatinib in gastrointestinal stromal tumor (GIST) represents a model for molecularly targeted therapy of solid tumors. Research is currently going to identify the molecular basis of mechanisms of action and drug resistance. For the optimal management of the patients treated, a multidisciplinary approach, including medical oncologists, surgeons, pathologists, and radiologists is needed. In this article, we reviewed recent advances in the clinical management of GIST patients treated with imatinib, and in the knowledge of the molecular mechanisms that are basic to imatinib effects.
    Reviews on Recent Clinical Trials 02/2007; 2(1):43-8.
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    ABSTRACT: Haematological toxicity characterized by delayed and reversible neutropenia and/or thrombocytopenia is an adverse effect observed in 40% of patients receiving fotemustine. We report the case of a 66-year-old man with metastatic malignant melanoma treated with fotemustine as monotherapy. A severe persistent and prolonged thrombocytopenia occurred, so that chemotherapy was discontinued. Bone marrow involvement was excluded. The physician should be aware of this prolonged thrombocytopenia secondary to fotemustine, so that it may be recognized early and not attributed erroneously to tumour evolution. This observation could be substantial for the design of combination regimens with fotemustine and other myelotoxic drugs in pretreated melanoma patients.
    Melanoma Research 01/2007; 16(6):543-4. · 2.52 Impact Factor
  • Supportive Cancer Therapy 10/2006; 4(1):63.
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    ABSTRACT: Thalidomide is a potent anti-myeloma drug which can produce up to a 30-50% overall response rate (ORR) in pre-treated, chemorefractory multiple myeloma. Most authors agree with using 200 mg/daily with associated high dose dexamethasone (40 mg/daily x 4 days, 3 times monthly) considering lower doses investigational. We report our experience using thalidomide 100 mg/daily plus dexamethasone 40 mg/daily once a month, in 27 pre-treated patients. Thalidomide dose excalation and/or association with other drugs were established on the basis of the patient's response. Median age was 69 years (range 50-83 years) and 16 male and 11 female patients were treated. All patients had received more than 1 treatment line (range 1-5). Thalidomide was increased up to 300 mg/daily in 10 patients and 1 patient received up to 400 mg/daily. Two patients were not evaluable because of early death, 1 did not tolerate thalidomide because of pulmonary and neurological side-effects. Sixteen patients responded to this treatment, with an ORR of 66%. The combination of low-dose thalidomide plus monthly high-dose dexamethasone in chemorefractory myeloma showed interesting palliative results. According to our data, increasing thalidomide dosage and/or adding further drugs does not generally produce significant improvement.
    In vivo (Athens, Greece) 01/2006; 20(6A):719-20. · 1.15 Impact Factor
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    ABSTRACT: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC) followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST), due to the typically hypervascular pattern of the tumor. We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Three patients (pts) with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.
    Journal of cancer research and therapeutics 01/2006; 2(2):68-71. · 0.83 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the activity and toxicity of electro-hyperthermia (ET) on relapsed malignant glioma patients. Twelve patients with histologically diagnosed malignant glioma entered the study. Eight patients had glioblastoma multiforme, two had anaplastic astrocytoma grade III and two had anaplastic oligodendroglioma. All patients were pre-treated with temozolamide-based chemotherapy and radiotherapy. Hyperthermia with short radiofrequency waves of 13.56 MHz was applied using a capacitive coupling technique keeping the skin surface at 20 degrees C. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumours was above 40 degrees C for more than 90% of the treatment duration. One complete remission and 2 partial remission were achieved, with a response rate of 25%. The median duration of response was 10 months (range 4-32). The median survival of the entire patient population was 9 months, with 25% survival rate at 1 year. ET appears to have some effectiveness in adults with relapsed malignant glioma.
    In vivo (Athens, Greece) 01/2006; 20(6A):721-4. · 1.15 Impact Factor
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    ABSTRACT: In the literature good results have been reported for the treatment of Pseudomyxoma peritonei (PMP) by cytoreduction, peritonectomy and hyperthermic antiblastic peritoneal perfusion (H.A.P.P.). Forty-eight patients affected by PMP have been treated with this technique over the past ten years. Peritoneal perfusion has been performed with the original semiclosed tecnique after complete surgical cytoreduction in 188 patients affected by peritoneal carcinomatosis. In 48 of the cases the patients were affected from PMP. Aggressive surgical cytoreduction was performed with multiple visceral resections and peritonectomies. Seventeen patients (38%) presented major perioperative complications, and in five cases the reoperation of the patient was required. In spite of this high complication rate, there was no perioperative mortality. The results of the Kaplan-Meier 5- and 10-year survival analysis, were 94% and 82%, respectively, with a disease-free survival of 80% at 5 years and 70% at 10 years. Thirty-nine patients (81.2%) had no evidence of disease at follow-up (range 1-120 months). Up to date, the most effective treatment for PMP has been aggressive cytoreduction plus H.A.P.P.
    In vivo (Athens, Greece) 01/2006; 20(6A):725-7. · 1.15 Impact Factor
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    ABSTRACT: Since November 2005 a clinical trial of intraarterial hepatic chemoembolization (TACE) with irinotecan-eluting beads has been ongoing in 20 patients affected by liver metastases from colorectal cancer in a palliative setting. A high response rate (80%), with reduction of lesional contrast enhancement in all responding patients was found. The procedure was well tolerated by most patients, with a median duration of hospitalization of 3 days (range 1-10 days). The most important adverse event was abdominal pain during the injection. Adequate supportive treatment with antibiotic and antiemetic prophylaxis, dexamethasone, and intravenous hydration is strictly necessary until the serum levels of transaminases are stabilized and in order to prevent infections. Major analgesics such as morphine must be used before and after the procedure. Our results suggest that TACE using irinotecan-eluting beads is feasible and active in pretreated patients with liver metastases from CRC.
    In vivo (Athens, Greece) 21(6):1085-91. · 1.15 Impact Factor
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    ABSTRACT: Intraperitoneal (IP) chemotherapy has been used in patients presenting different stages of ovarian cancer. We performed a critical review of the available literature on IP as first-line treatment in advanced ovarian cancer to consider if this new option should be incorporated into the commonly applied guidelines for treatment of ovarian cancer. We concluded that without further data, it would not be ethically correct to administer chemotherapy intraperitoneally. Outside of planned clinical trials, patients should not be exposed to this treatment modality and its associated toxicity. The present international guidelines are still valid and recommended chemotherapy in advanced ovarian cancer remains treatment with paclitaxel and carboplatin. Further studies on this topic are, however, warranted.
    In vivo (Athens, Greece) 23(2):317-21. · 1.15 Impact Factor
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    ABSTRACT: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and the liver is the predominant site of metastases (LM). If metastases appear, none of the systemic treatments established for cutaneous melanoma so far have any significant impact. Several authors have adopted transarterial chemoembolization (TACE) as palliation. TACE combines hepatic artery embolization with infusion of concentrated doses of chemotherapeutic drugs. DC Beads are new embolic products that can be loaded with irinotecan (IRI). The beads consist of polyvinyl alcohol microspheres modified with sulfonic acid groups and are available at different size ranges from 100 to 900 microns in diameter. The use of IRI as drug-eluting beads seems to optimize TACE in UM. Our purpose was to assess the safety and efficacy of this new kind of TACE in a phase II clinical study. Ten patients with LM from UM were treated with TACE-containing beads preloaded with IRI (100 mg). All patients had an objective response, three presented a very good partial response and seven obtained a partial response. The median follow-up time from the beginning of therapy was 6.5 months (range 4-9 months). Eight patients are alive at the time of this analysis. The most important adverse event was abdominal pain during the procedure. Adequate supportive treatment with antibiotic and antiemetic prophylaxis, desametazone and intravenous hydration is strictly necessary until stabilization of serum levels of transaminases and to prevent infections. A major analgesic such as morphine must be used before and after the procedure. TACE containing beads preloaded with IRI is effective in the treatment of LM from UM. This approach seems to have better efficacy than previous TACE regimens adopted.
    In vivo (Athens, Greece) 23(1):131-7. · 1.15 Impact Factor
  • Hepato-gastroenterology 54(77):2 p preceding table of contents. · 0.77 Impact Factor
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    ABSTRACT: Hepatic arterial infusion (HAI) chemotherapy is accepted to be an option in patients with non-resectable metastases from colorectal cancer confined to the liver. In a multi-istitutional trial, 76 patients were randomly assigned to receive HAI versus HAI plus systemic bolus 5-fluorouracil and leucovorin. The primary endpoint was survival, followed by response, recurrence and toxicity. Survival was longer for HAI plus systemic chemotherapy (HAI+SYC) than HAI (median, 20 vs. 14 months; p = 0.0033), as were responses (47.5% and 41.7%; p = 0.09) and time to hepatic progression (12 vs. 8 months; p = 0.039). Side effects included haematological toxicity that was mostly mild and reversible in 432 cases. Neutropenia grade 3 occurred in four patients in the HAI+SYC arm and one in the HAI arm. Diarrhoea occurred in 20% and 7% of patients and stomatitis occurred in 18% and 2%, respectively. On the contrary biliary toxicity was significant; twelve patients had evidence of bilirubin elevations of more than 3 mg/dl (six in each arm), and two had asymptomatic arterial biliary-tree fistulae: one in the HAI+SYC arm and one in the HAI arm. Grade 3 elevation in alkaline phosphatase and aminotransferase levels occurred in 26% and 24%, respectively. In conclusion, the combination of HAI+SYC is active and safe showing a clinical advantage with respect to simple HAI, increasing overall survival, response rate and time to progression.
    In vivo (Athens, Greece) 20(6A):707-9. · 1.15 Impact Factor
  • Tumori 92(5):465-6. · 0.92 Impact Factor
  • Tumori 92(3):267; author reply 268. · 0.92 Impact Factor