Luigi Mariani

Istituto Nazionale Tumori "Fondazione Pascale", Napoli, Campania, Italy

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Publications (266)1588.24 Total impact

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    ABSTRACT: In the late Nineties the use of high-dose chemotherapy (HDCT) and stem cell rescue held promise for patients with advanced and poor prognosis germ cell tumors (GCT). We started a randomized phase 2 trial to assess the efficacy of sequential HDCT compared to cisplatin, etoposide, and bleomycin (PEB).
    Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 10/2014;
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    ABSTRACT: To explore patterns of failure and postrelapse outcome of patients with retroperitoneal sarcoma primarily treated by extended resection.
    Annals of Surgical Oncology 10/2014; · 4.12 Impact Factor
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    ABSTRACT: Outcomes of radiotherapy (RT) compared to chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma.
    Annals of Oncology 09/2014; · 7.38 Impact Factor
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    ABSTRACT: Extracorporeal photochemotherapy (ECP) is a treatment approved by the FDA for cutaneous T-cell lymphoma, and it is currently used off-label for graft-versus-host disease (GvHD) and other conditions. In agreement with good practices for the therapeutic use of human cells, quality control has to be performed to validate the ECP procedure with the off-line technique. Since no gold-standard biological test is available, we assessed the apoptosis generated in the ECP bag using a flow cytometric analysis. Thirty-one ECP procedures performed on 13 patients with chronic GvHD were studied by monitoring the induction of mononuclear cell (MNC) apoptosis using annexin V/propidium iodide double staining; residual lymphocyte proliferation to standard mitogens was also measured in 17 of the procedures. The kinetics of apoptosis was analyzed at different times in MNCs untreated or treated with 8-methoxy-psoralen plus ultraviolet A; the variation (ΔAPOPTOSIS) after 24 h revealed the efficacy of the treatment. In 88.6% of the 31 ECP procedures, ΔAPOPTOSIS was >15% (the “alerting” threshold for ΔAPOPTOSIS was set at 15% on the basis of our data); in the remainder (19.4%), the increment in apoptosis was lower. In four procedures, the proliferation assay was useful for assessing the effect of ECP on the apheretic bag. In conclusion, both flow cytometric assays enabled a biologically significant result to be obtained. In our opinion, the apoptosis test—being faster and easier than the proliferation test—could be a reliable way to validate ECP procedures. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Clinical Apheresis 09/2014; · 2.27 Impact Factor
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    ABSTRACT: Cutaneous melanoma incidence is increasing. Most new cases are thin (≤ 1 mm) with favorable prognoses, but survival is nonetheless variable. Our aim was to investigate new prognostic factors and construct a nomogram for predicting survival in individual patients.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 07/2014;
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    ABSTRACT: Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis.
    Clinical Genitourinary Cancer 06/2014; · 1.43 Impact Factor
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    ABSTRACT: Background: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting. Methods: We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28). Results: Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes. Conclusion: TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease. © 2014 S. Karger AG, Basel.
    Oncology 06/2014; 86(5-6):289-294. · 2.17 Impact Factor
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    ABSTRACT: This randomized double-blind study was designed to determine if respiratory muscle weakness - measured by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) - persists even if an acceleromyographic train-of-four ratio (TOFR) of 1.0 is reached after major abdominal surgery. Twenty patients underwent respiratory function tests before induction of anesthesia. Rocuronium was given, and the tests were repeated after extubation when the TOFR reached 1.0. The patients were then randomized to receive sugammadex 1 mg·kg(-1) or placebo, and the same tests were repeated five and 20 min later. Between-group comparisons were carried out with a mixed-model analysis of variance analysis. After anesthesia and adequate epidural analgesia, MIP and MEP decreased by 60% in both groups. In the placebo group, MIP decreased from a pre-induction value (median [range]) of 61.8 [31.3-96.1] to 19.6 [8.3-58.3] cm H2O after extubation without significant variation five and 20 min after placebo. In the sugammadex group, MIP decreased from a pre-induction value of 57.8 [13.0-96.4] to 20.5 [6.4-67.3] cm H2O after extubation. No differences were recorded after sugammadex administration (P = 0.246 between groups). In the placebo group, MEP decreased from 88.8 [65.1-120.3] before induction to 37.6 [13.4-70.6] cm H2O after extubation. In the sugammadex group, MEP decreased from 85.5 [58.6-132.7] to 30.8 [10.5-60.5] cm H2O, with no improvement five and 20 min after either placebo or sugammadex administration (P = 0.648). Similarly, the FCV and FEV1 decreased 30-40% after extubation in both study groups. Acceleromyographic TOFR of 1.0 excludes residual neuromuscular paralysis. However, major respiratory dysfunction is observed after abdominal surgery. This trial was registered at ClinicalTrials.gov: NCT01503840.
    Canadian Anaesthetists? Society Journal 04/2014; · 2.31 Impact Factor
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    ABSTRACT: Despite a compelling preclinical rationale for the use of anti-angiogenic drugs in urothelial cancer (UC), short-living responses have been observed in clinical trials. PF-03446962 is a novel monoclonal antibody against Activin Receptor-Like Kinase-1 (ALK1), a type I subclass of the TGFβ receptor, with dose-dependent anti-angiogenic activity. An open label, single-group, phase 2 trial of PF-03446962 was conducted in salvage setting. Patients failing at least one chemotherapy regimen were eligible. Design provided PF-03446962 10 mg/Kg intravenously fortnightly until disease progression (PD) or unacceptable toxicity. Two-month progression-free survival (PFS) was the primary endpoint. The trial was registered with ClinicalTrials.gov, number NCT01620970. Fourteen patients were enrolled from October 2012 to July 2013. Median age was 64 years (interquartile range [IQR]: 58.2-69.5), 9 patients had a Bellmunt score of 1-2, median number of prior drugs was 3. One stable disease and 13 PD were recorded and the study met the futility stopping rule of interim analysis. Median PFS was 1.8 months (95 %CI, 1.4-2.0). After a median follow up of 7.4 months (IQR 4.5-10.9), 8 patients are alive. Median overall survival (OS) was 8 months (95 %CI, 2.9-not estimable). Most common toxicities were thrombocytopenia (G1-2 in 5 cases, persistent G3 in one, with 3 dose delays and 1 dose interruption), fatigue and abdominal pain (G1-2 in 4 cases each). Impairment of quality of life (ESAS score) was observed as well as an increase from baseline to +2 month median levels of vascular endothelial growth factor (VEGF) and interleukin-8. PF-03446962 had no activity as single drug in refractory UC and we do not recommend further investigation outside of the combination with agents targeting the VEGF receptor axis.
    Investigational New Drugs 02/2014; · 3.50 Impact Factor
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    ABSTRACT: To date, no treatment modality has been identified as more effective for oropharyngeal cancer (OPC), and no predictive factors are known to guide treatment decision for this disease. This retrospective study evaluates the differential effects of diverse treatment options for OPC according to patient risk profiles. We considered two series of locally advanced squamous cell OPC patients treated with either surgery followed by radiotherapy (surgical series) or chemoradiation (CRT) with/without induction docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CRT series). Smoking habits, tumor p16 expression/human papillomavirus (HPV) status and T and N stage were analyzed to stratify the patients according to Ang's risk profile (low, intermediate and high risk). Overall survival (OS) and disease-free survival were calculated with the Kaplan-Meier method. Globally, 171 patients were considered, 56 in surgical and 115 in CRT series. Patients were stratified in low- (20% of surgical and CRT groups), intermediate- (23% and 41%) and high-risk (57% and 39%) groups. In the surgical series, 5-year OS was 54.5%, 46.9% and 40.0% in low, intermediate and high Ang's risk profiles, respectively, whereas in the CRT series those were 100%, 78.9% and 46.7%, respectively. In the multivariable analyses, adjusting for inhomogeneity between the treatment group, the CRT effect was significantly higher in the low- and intermediate-risk groups (P-value for the interaction treatment risk group = 0.034 in the OS analysis). In this retrospective analysis, low- and intermediate-risk OPC patients had a better survival when treated with CRT compared with open surgery followed by radiation therapy. These data suggest that different treatment approaches might be essential in determining outcome results.
    Annals of Oncology 02/2014; · 7.38 Impact Factor
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    ABSTRACT: Purpose Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter (90Y) and a medium-energy beta/gamma emitter (177Lu) in patients with metastatic NET refractory to conventional therapy. Methods A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [177Lu]DOTA-TATE (5.55 GBq) and [90Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [177Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Results Administration of tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment Conclusion The results of our study indicates that combined [90Y]DOTA-TATE and [177Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.
    European journal of nuclear medicine and molecular imaging 02/2014; 41(2). · 5.11 Impact Factor
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    ABSTRACT: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices.
    Annals of Oncology 01/2014; · 7.38 Impact Factor
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    ABSTRACT: Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer. A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m(2) and fluorouracil 1000 mg/m(2) (120-h infusion administered every 21 days) in stage T2-T4, N0-N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death. Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P = 0.6337), nor in distant metastasis development (P = 0.1527). There was also no difference between groups in overall survival (P = 0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P = 0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%). Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.
    Annals of Oncology 01/2014; · 7.38 Impact Factor
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    ABSTRACT: Aims The purpose of this observational study was to evaluate disease free survival (DFS), overall survival (OS), and local recurrence rate (LRR) in patients submitted to Class II RH compared with Class III RH in early FIGO stage cervical cancer (ECC). Materials and Methods We investigated 127 patients with CC admitted to the National Cancer Institute of Milan from June 2001 to October 2011 treated with Class II RH, and compared them with 202 patients operated with Class III RH between March 1980 and March 2001. A total of 329 patients were collected. Results Median follow-up time was 91 months (IQ range:58-196). Five-year OS and DFS estimates were 89.5% (95%CI: 86.0-93.2%) and 85.6% (95%CI: 81.6-89.7%), respectively. Estimates of effect of surgical treatment (Class III RH versus Class II RH) on OS showed a HR of death= 3.38 (95%CI: 1.18-9.63, P=0.0228), at univariable Cox analysis, and a HR= 3.08 (95%CI: 0.96-9.93; P= 0.0595) at multivariable analysis. For DFS, a HR of relapse=2.51 (95%CI 1.10-5.72; P=0.0290) comparing Class III vs Class II was found at multivariable analysis. Overall recurrence rate was 12.8%, whilst it was 16.3% for Class III and 7.1% for Class II respectively. Conclusions The present data suggest that the outcomes of Class II RH are comparable in terms of LRR and OS to those of Class III RH, according to literature data. The opportunity of extending the indication to all women with ECC needs further investigations. Clearer data are warranted by prospective controlled studies
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2014; · 2.56 Impact Factor
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    ABSTRACT: Background The prognostic impact of early metabolic response by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) after 2 cycles of first-line chemotherapy is still unrecognized in metastatic transitional cell carcinoma (TCC). Patients and Methods Patients with metastatic TCC receiving the modified combination of methotrexate, vinblastine, doxorubucin, and cisplatin (MVAC), according to Institutional protocol, underwent computed tomography (CT) and FDG-PET at baseline, a restaging with PET after 2 cycles only (PET2), and a CT (± FDG-PET) at the end of treatment and during follow up. Progression-free (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method; univariable (UVA) and multivariable (MVA) Cox models were fitted. Pre-specified variables were the presence of visceral metastases, nodal or soft tissue disease, and early PET response. Results In the time-frame 05/2010-10/2012, 31 patients with ECOG-PS 0 received the modified MVAC regimen, every 3 weeks. Six patients (19.3%) had a complete (CR) and 17 (54.8%) a partial metabolic response (PR), 4 had stable disease (SD), 4 progressed. PET2 responders had a median (95% confidence interval [CI]) progression-free survival (PFS) of 8 (7-11) months compared to 3 (2-5) months of patients without response (p=0.024). They also had a significant benefit in 8-month PFS (p<0.001 at Klein test) and 15-month overall survival (OS, p=0.016). PET2 response was significant for PFS in both UVA and MVA (p=0.027 and p=0.023, respectively). Conclusion PET response after 2 cycles of first-line chemotherapy was associated with longer PFS and OS in advanced TCC and warrants further investigation in the field, compared to early CT.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: Background Knowledge of the expression of molecular drivers and potentially druggable targets may enhance prognostic classification of metastatic urothelial carcinoma (UC). Materials and Methods We analyzed archival tissue from patients with UC undergoing first-line chemotherapy for locally-advanced (LA) and metastatic (M) disease between the years 2000 and 2013. The following biomarkers were evaluated by immunohistochemistry (IHC): ERCC1, EGFR, HER2, VEGFR-3, PDGFRα, p53, p63. Expression of ERCC1, EGFR, and HER2 was dichotomized as positive (2+,3+) or negative (≤1+). Cox regression models evaluated the association of biomarker expression with progression-free (PFS) and overall survival (OS), after controlling for known prognostic factors. Results Since 06/2009, tissues of 88 cases (27 LA, 61 M) have been stained. Rates of positive IHC/number evaluable were as follows: ERCC1: 30/66 (45%); HER2: 24/52 (46%); EGFR: 31/54 (57%); VEGFR-3: 50/66 (76%); PDGFRα: 10/63 (16%); p53: 25/56 (45%); p63: 46/53 (87%). In the multivariable model, PDGFRα was significantly prognostic for poorer PFS (HR: 2.53, 95%CI, 1.01-6.37, p=0.047) and trended to significance for poorer OS (HR: 2.66, 95%CI, 0.96-7.42, p=0.060) while VEGFR-3 was significantly prognostic for both better PFS (HR: 0.33, 95%CI, 0.15-0.74, p=0.007) and OS (HR: 0.36, 95%CI, 0.15-0.85, p=0.019). The c-index of the model was 0.67 and 0.68 for the two endpoints, respectively. Conclusions Tumor VEGFR-3 and PDGFRα expression appeared to confer a divergent prognostic impact. These data underscore the hurdles in defining the role of angiogenesis as a molecular driver and therapeutic target, as well as the controversial role of IHC to guide therapeutic decision-making.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
  • Federico Bozzetti, Luigi Mariani
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    ABSTRACT: Objective The results achieved through the Enhanced Recovery After Surgery (ERAS) approach in the gastrointestinal surgery has led to its enthusiastic acceptance also in pancreatic surgery. However the ERAS programme also involves an early oral feeding that is not always feasible after pancreatoduodenectomy. We investigated in the literature whether the difficulty with an early oral feeding was adequately balanced by a perioperative enteral or parenteral nutritional support as recommended by the ESPEN Guidelines in these patients or whether these recommendations have lost value in the “bundle” of the ERAS. Methods We reanalyzed both ESPEN guidelines and literature regarding ERAS programme in surgical pancreatic patients. Results There was a high prevalence of malnutrition (and consequently of postoperative complications) in pancreatic cancer patients, and there is evidence that many of these patients should be candidate for a perioperative nutritional support according to the ESPEN guidelines. The start of oral fluid and solid feeding was quite variable in literature reporting the use of ERAS in pancreatic cancer surgery, with consistent gap between the recommended and the effective start of both the feedings. The use of nasogastric/jejunal tube or of a needle-catheter jejunostomy was discouraged by the ERAS guidelines but their use can prove beneficial in patients who are recognized at high risk for postoperative complications according to the scores available in literature. Conclusion The current practice of the ERAS programme in these patients appears to neglect some ESPEN recommendations. On the contrary both ESPEN and ERAS recommendations could combine together with a supplemental benefit for the patient.
    Nutrition. 01/2014;
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    ABSTRACT: Background The contribution of postchemotherapy pelvic (PLND) or retroperitoneal lymphadenectomy (RPLND) on survival in patients with advanced and metastatic urothelial carcinoma (UC) is still unclear. Patients and Methods Between September 1986 and May 2012, 157 patients with locally advanced or metastatic urothelial cancer received first-line chemotherapy consisting of the modified methotrexate, vinblastine, doxorubicin, and cisplatin (mMVAC), according to our policy. Patients having subdiaphragmatic nodal disease/local recurrence only and experiencing at least a stable disease were selected. Fifty-nine patients were identified, 28 of whom underwent surgery, 31 started consolidation chemotherapy±radiotherapy or observation. The prognostic effect of candidate factors upon survival was evaluated by using Cox proportional hazard regression models. Results A total of 14 PLND and 14 RPLND were identified after achieving a complete response (CR, N=7) or a partial response-stable disease (PR+SD, N=21). Median follow-up was 88 months (IQR: 24-211). Median progression-free (PFS) survival was 18 (95%CI, 11-not estimated) and 11 (95%CI, 5-19) months, respectively in favor of surgical cohort and curves were statistically different (log-rank test p=0.009). On multivariate analysis, post-chemotherapy surgery was significantly prognostic for both PFS and OS and response to chemotherapy (PR/SD vs CR) was prognostic for PFS and trended to significance for OS. A model including these two factors showed a bootstrap-corrected Harrel C statistics for PFS and OS of 0.65 and 0.68, respectively. Conclusions In well selected patients with UC like those achieving a clinical benefit with chemotherapy and having nodal metastatic disease there was a survival advantage by removing disease residuals.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: The classic MVAC (methotrexate/vinblastine/doxorubicin/cisplatin) regimen was the first recognized option for untreated patients with locally advanced or metastatic urothelial cancer (UC). Modifying MVAC by reducing side effects may have the potential to improve efficacy. Changes to classic MVAC were provided at the authors' institution: (1) deletion of day 22 and administration of 25 mg/m(2) cisplatin on days 2 to 5 (modified [m]MVAC); (2) deletion of day 22 only (simplified [s]MVAC1); and (3) deletion of days 15 and 22 in a 3-week schedule (sMVAC2). A total of 4 to 6 cycles were provided. Multivariate analysis was undertaken for recognized clinical variables. For the period from September 1986 to May 2012, 157 patients were identified (25 with mMVAC, 72 with sMVAC1, and 60 with sMVAC2). Overall, 43.9% had a Memorial Sloan-Kettering Cancer Center score of 1 or 2, with differences across series (P = .002). Altogether, 65.8% attained a complete (19.1%) or partial response (46.7%), and 24.3% a stable disease, with no difference across regimens. After a median follow-up of 87 months (interquartile range, 37-161), median progression-free survival was 10.2 months (95% CI, 8.4-10.8), and median overall survival (OS) was 19.5 months (95% CI, 16.3-24.1). Responses were mainly seen in nodal metastases or soft tissue relapse (odds ratio, 2.48; 95% CI, 1.12-5.54). Only visceral (hazard ratio [HR], 2.42; 95% CI, 1.37-4.30) and nodal metastases/local relapse (HR, 1.70; 95% CI, 1.07-2.69) were independently associated with OS. Grade 3 or 4 toxicities were similar across regimens and were 36% neutropenia, 14% thrombocytopenia, 12% anemia, 10% mucositis, and 4% renal toxicity. Two treatment-related deaths occurred. Simplifying MVAC may result in improved efficacy and reduced toxicity. The combined results of the original and modified MVAC regimens encourage a reappraisal of the frontline management of advanced UC.
    Clinical Genitourinary Cancer 11/2013; · 1.43 Impact Factor
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    ABSTRACT: Background:Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients.Methods:EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model.Results:Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level80.Conclusion:IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.British Journal of Cancer advance online publication, 14 November 2013; doi:10.1038/bjc.2013.719 www.bjcancer.com.
    British Journal of Cancer 11/2013; · 5.08 Impact Factor

Publication Stats

9k Citations
1,588.24 Total Impact Points

Institutions

  • 1998–2014
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1995–2014
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • • s.c. Medicina Oncologica 1
      • • s.c. Pediatria Oncologica
      Milano, Lombardy, Italy
  • 2007–2012
    • CRO Centro di Riferimento Oncologico di Aviano
      • Department of Surgery
      Aviano, Friuli Venezia Giulia, Italy
    • IEO - Istituto Europeo di Oncologia
      Milano, Lombardy, Italy
    • Prato Ricerche
      Prato, Trentino-Alto Adige, Italy
  • 2010
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France
  • 1998–2010
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1997–2010
    • University of Milan
      • Faculty of Medicine
      Milano, Lombardy, Italy
  • 2009
    • Università degli Studi di Milano-Bicocca
      Milano, Lombardy, Italy
  • 2007–2009
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 2005
    • A.C.O. San Filippo Neri
      Roma, Latium, Italy
  • 1990
    • Italian National Institute of Statistics
      Roma, Latium, Italy