Musso M.,La Maddalena Hospital |
Messina G.,Hematology and Stem Transplantation Unit |
Marcacci G.,Instituto Of Ricovero E Cura A Carattere Scientifico |
Crescimanno A.,La Maddalena Hospital |
And 5 more authors.
Biology of Blood and Marrow Transplantation | Year: 2015
High-dose melphalan (MEL) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Thiotepa (THIO) appears to be a potentially effective option, with broad-spectrum antitumor efficacy that can be added to myeloablative multiagent regimens for ASCT in hematopoietic tumors. We conducted a phase II trial, adding THIO (275 mg/m2) to high-dose MEL (140 mg/m2) before a second ASCT, in a tandem ASCT strategy, in 64 patients with "de novo" MM. Overall, there was no transplant-related mortality. The incidence of neutropenic fever and mucositis (grades 3 to 4) was 39% and 9%, respectively. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response improved to 43.8%. Overall response rate was 86%. After a median follow-up of 18.1 months, 13 patients had progressed and 3 died from MM. Median progression-free survival was not reached, and actuarial 2-year rates of progression-free and overall survival were 71% and 88.9%, respectively. Our results suggest that THIO/MEL is a feasible and safe conditioning regimen for ASCT in MM and should be explored for efficacy in a phase III study. © 2015 American Society for Blood and Marrow Transplantation.
Marengo G.,La Maddalena Hospital |
Cancemi P.,University of Palermo |
Pucci-Minafra I.,Centro Of Oncobiologia Sperimentale Cobs
Anticancer Research | Year: 2013
Background: The Human Epidermal Growth Factor Receptor 2 (HER-2), overexpressed in 25-30% of breast carcinomas (BC), is the therapeutic target for trastuzumab, a recombinant humanized monoclonal antibody. The initial response to trastuzumab is often followed by drug-insensitivity within one year. Several hypotheses have been raised to explain this event, but the mechanisms behind the responses to trastuzumab are still unclear. Aim: To study the effects of short and prolonged trastuzumab treatment on the proteomic profiles of HER-2- overexpressing SKBR-3 BC cells. Materials and methods: Cells were treated with trastuzumab to obtain sensitive and resistant clones. The drug effects were evaluated at the phenotypical and proteomic levels. Results: In the trastuzumab-resistant cells the expression of a large amount of proteins, initially affected by treatment, reverted to levels of the untreated cells. Conclusion: The results obtained so far illustrate for the first time a large-scale differential protein expression between trastuzumab-treated and untreated cells, and between trastuzumab-sensitive and resistant cells. We believe that the results obtained will help to increase the knowledge of the molecular effects of trastuzumab and will be useful to better-understand the drug resistance mechanisms. © 2013 Anticancer Research.
PubMed | Hematology and Stem Transplantation Unit, La Maddalena Hospital and Instituto Of Ricovero E Cura A Carattere Scientifico
Type: Clinical Trial, Phase II | Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation | Year: 2015
High-dose melphalan (MEL) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Thiotepa (THIO) appears to be a potentially effective option, with broad-spectrum antitumor efficacy that can be added to myeloablative multiagent regimens for ASCT in hematopoietic tumors. We conducted a phase II trial, adding THIO (275 mg/m(2)) to high-dose MEL (140 mg/m(2)) before a second ASCT, in a tandem ASCT strategy, in64 patients with de novo MM. Overall, there was no transplant-related mortality. The incidence of neutropenic fever and mucositis (grades 3 to 4) was 39% and 9%, respectively. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response improved to 43.8%. Overall response rate was 86%. After a median follow-up of 18.1 months, 13 patients had progressed and 3 died from MM. Median progression-free survival was not reached, and actuarial 2-year rates of progression-free and overall survival were 71% and 88.9%, respectively. Our results suggest that THIO/MEL is a feasible and safe conditioning regimen for ASCT in MM and should be explored for efficacy in a phase III study.
Gallamini A.,S Croce Hospital |
Patti C.,Cervello |
Viviani S.,Instituto Nazionale Tumori |
Rossi A.,Ospedali Riuniti di Bergamo |
And 16 more authors.
British Journal of Haematology | Year: 2011
Interim 2-[18F]Fluoro-2-deoxy-D-glucose Positron Emission Tomography performed after two chemotherapy cycles (PET-2) is the most reliable predictor of treatment outcome in ABVD-treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET-2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET-2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score (Meignan, 2009). After a median follow up of 34months (12-52) the 2-year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET-2 positive and 92% for PET-2 negative patients. For 154 patients in which treatment was correctly given according to PET-2 review, the 2-year FFS was 91%: 62% for PET-2 positive and 95% for PET-2 negative patients. Conclusions: this strategy, with BEACOPP intensification only in PET-2 positive patients, showed better results than ABVD-treated historic controls, sparing BEACOPP toxicity to the majority of patients (Clinical Trials.gov Identifier NCT00877747). © 2011 Blackwell Publishing Ltd.
Cisplatin, fotemustine and whole-brain radiotherapy in non-small cell lung cancer patients with asymptomatic brain metastases: A multicenter phase II study of the Gruppo Oncologico Italia Meridionale (GOIM 2603)
Galetta D.,Giovanni Paolo II Oncology Institute |
Gebbia V.,La Maddalena Hospital |
Silvestris N.,Giovanni Paolo II Oncology Institute |
Ferrau F.,Taormina Hospital |
And 6 more authors.
Lung Cancer | Year: 2011
Background: More than 50% of brain metastases (BMs) occur in advanced non-small cell lung cancer (NSCLC) patients. Untreated patients with BMs have a poor prognosis with a median survival of 2 months. In most cases BMs are multiple and their optimal therapy is whole-brain radiation therapy (WBRT). The role of systemic therapies for these patients is still a matter for investigation due to concerns about the ability of these drugs to cross the blood-brain barrier (BBB). Cisplatin (CDDP) remains the backbone for medical treatment of NSCLC and fotemustine (FTM) is a nitrosurea able to cross the BBB. Methods: Patients with advanced NSCLC, ECOG performance status (PS) 0-1 and multiple BMs not amenable to surgery or stereotactic radiotherapy were treated with 2 cycles of FTM 80mg/m2 days 1, 8 and CDDP 80mg/m2 day 1, every 3 weeks followed by WBRT 30Gy (3Gy daily in 10 fractions). Radiological restaging was performed before WBRT to assess the role of chemotherapy both for cranial and extracranial disease. Patients with disease control (DC: complete response plus partial response) received 4 more cycles. To assess the basic activities of daily living (ADL), the Barthel ADL Index was used to score patients' performance every 2 cycles. The trial design provides a two-step evaluation according to the optimal two-stage design of Simon. In the first phase 29 patients were enrolled in order to verify if this schedule showed more than 25% response rate both for cranial and extracranial disease. If so, enrolment added up to a total of 81 patients. Results: After the first evaluation 4 out of 29 patients were excluded from the study (3 untreated/1 not included for administrative reasons). At the time of the planned interim analysis patient's characteristics were the following: median age 61 years (range 44-70), M/F. =16/9, adenocarcinoma 11, squamous 5, large cell 2, undefined NSCLC 7; PS 0/1 in 11/14 cases, median Barthel Index score was 20 [13-20]. Three (12%) partial responses were observed, 9 subjects (36%) with stable disease and 13 (52%) showing disease progression. These data did not satisfy the pre-planned hypothesis and the study was stopped. At the time of the first evaluation before WBRT 12/25 (48%) patients had a systemic DC in contrast with 15/25 (60%) patients with BMs DC. Chemotherapy was relatively well tolerated with a prevalence of asthenia as the most relevant specific toxicity while the haematological toxicity was mild. Conclusion: CDDP and FTM combined with WBRT do not represent a therapeutic option for patients with NSCLC. Therefore further studies to evaluate the combination of systemic treatments with WBRT are warranted. © 2010 Elsevier Ireland Ltd.
PubMed | Italian National Cancer Institute, La Maddalena Hospital, Ospedali Riuniti Hospital, Cardarelli Hospital and 7 more.
Type: Clinical Trial, Phase III | Journal: International journal of oncology | Year: 2014
We conducted a phase III multicenter randomized trial to compare the efficacy of the combination of liposome encapsulated doxorubicin (Myocet()) plus either cyclophosphamide (MC) or vinorelbine (MV). Since July 2006, 233 patients affected with metastatic breast cancer were randomized to receive the combination of Myocet (M) 60 mg/m(2) i.v. plus cyclophosphamide (C) 600 mg/m2 on Day 1 of a 21day cycle (Arm A) or Myocet (M) at 50 mg/m2 plus vinorelbine (V) 25 mg/m2 i.v. on Day 1 and V 60 mg/m2 orally on Day 8 on a 21day cycle (Arm B). The primary endpoints of the study was time to progression (TTP); secondary endpoints were RR, toxicity and OS. Response was observed in 53/116 (45.7%) evaluable patients of Arm A vs. 51/112 (45.5%) of Arm B, respectively (P=NS). Median TTP was 41 weeks (95% CI, 3251) and 34 weeks (95% CI, 2639), for M/C and M/V, respectively (P=0.0234). The difference in median OS was not statistically significant (131 vs. 122 weeks; P=0.107). With regard to toxicity, patients treated with MV showed a slight increase of neutropenia and constipation, as compared to those treated with MC. No clinical signs of cardiotoxicity were observed. The MC combination remains as an unbeaten standard in first line treatment of MBC.
Cistaro A.,Positron |
Cistaro A.,National Research Council Italy |
Quartuccio N.,Messina University |
Caobelli F.,Hannover Medical School |
And 6 more authors.
Nuclear Medicine Review | Year: 2015
Neuroblastoma is the most common extra-cranial solid tumor in pediatric patients. Despite the established role of 123I-MIBG and 131I-MIBG scintigraphy in this tumor, only limited data are available regarding the use of 124I-metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed tomography (CT). We present our preliminary experience with 124I-MIBG PET/CT: two pediatric patients affected by neuroblastoma, who underwent 124I-MIBG PET/CT for pre-therapy distribution evaluation and restaging purposes. We aimed to evaluate whether 124I-MIBG PET/CT can detect as many or more neuroblastoma lesions than 123I/131I-MIBG imaging. Our cases show promising results, although further validation and standardization of 124I-MIBG PET/CT are required. Copyright © 2015 Via Medica.
Cistaro A.,Positron |
Quartuccio N.,Messina University |
Mojtahedi A.,Sloan Kettering Cancer Center |
Fania P.,Positron |
And 4 more authors.
Radiology and Oncology | Year: 2013
Background. The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up. Patients and methods. Forty-nine patients with stage I-II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography (18F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated. Results. There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9. Conclusions. In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.
Lombardi L.,Oncology Unit |
Gebbia V.,La Maddalena Hospital |
Silvestris N.,Cancer Institute Giovanni Paolo II |
Testa A.,La Maddalena Hospital |
And 2 more authors.
Oncology | Year: 2010
Colon cancer is the second leading cause of cancer death worldwide. Approximately three quarters of patients are diagnosed with disease limited to the bowel wall or surrounding lymph nodes. Over the past decade, significant progress has been made in the treatment of localized colon cancer. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid. In stage II, the value of post-operative treatment remains controversial, but the identification of histopathological and molecular prognostic factors would allow selection of patients who can benefit from adjuvanttreatment. The inclusion of molecular targeted agents in combination regimens with cytotoxins, which have already proven effective in advanced disease, is the main field of development in the most recent protocols of adjuvant therapy. Copyright © 2010 S. Karger AG.
PubMed | La maddalena hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
7314 Background: A number of second line treatments have been proposed in patients (pts) with advanced pretreated NSCLC. However, either single agents or two or three drug combinations achieved very poor results with no superiority of any combination over single agents.In this study we have treated 42 pts affected by advanced NSCLC previously submitted to chemotherapy (CT) with topotecan (1.2 mg/mPartial response (PR) was observed in 5/41 pretreated pts (12,2%) and in the nave patient. In addition, one (2,4%) minimal (<50%) response (MR) plus 14 (34%) stable disease (SD) and 21(51%) progressive disease (PD) were observed. Grade 3-4 neutropenia was the dose limiting toxicity, observed in 36% of pts. Moreoveer, grade 3-4 anemia was observed in 17% and grade 3-4 thrombocytopenia in 12% of pts, respectively. One PS 2 patient died for grade 4 hematological toxicity after the first cycle. Median survival for the entire group was 26 weeks (range 1-91+) with 14% of pts alive at one yr.In conclusion, the combination of topotecan and ifosfamide demonstrated antitumor activity with modest side effect profile in patients with previously treated NCSLC, with an overall disease control (PR+MR+SD) of 48.8%. Nevertheless, the still low response rate and the shortness of median survival claim for more effective second line treatments in this disease. No significant financial relationships to disclose.