Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Database
Language
Publication year range
1.
Cancer Biol Ther ; 19(8): 659-663, 2018 08 03.
Article in English | MEDLINE | ID: mdl-29580164

ABSTRACT

Tumors represent a dynamic system where the genomic plasticity permits to adapt to the perturbation induced by environmental pressures, supporting the importance of longitudinal tumor sampling strategies to deciphering the temporal acquisition of driver event that could impact treatment outcome. We describe the case of a metastatic colorectal cancer (mCRC) patient, RAS wild-type, who responded to anti-EGFR therapy and underwent liver surgery, revealing a KRAS mutations in the metastatic lesion, not detectable prior to initiation of therapy in the colonic biopsy. After liver surgery, the patient received chemotherapy alone, then underwent left colectomy and the final pathological report confirmed the KRAS wild-type status. We can speculate the existence of two distinct populations of KRAS wild-type and mutant CRC cells sharing the same genetic origin. The anti-EGFR treatment represented a selective pressure which allowed the selection of KRAS mutant subclones. The prognostic and /or predictive role of intratumor heterogeneity has not been assessed prospectively. Our case report is of clinical relevance because patients with mCRC who respond to anti-EGFR antibodies often develop resistance within several months of initiating therapy, thus outlining the importance to better ascertain the molecular landscape of tumors to design better therapeutic strategies.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Colorectal Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Female , Humans , Immunohistochemistry , Liver Neoplasms/diagnosis , Liver Neoplasms/drug therapy , Molecular Targeted Therapy , Proto-Oncogene Proteins p21(ras)/metabolism , Tomography, X-Ray Computed , Treatment Outcome
2.
Eur J Surg Oncol ; 43(4): 735-742, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28131670

ABSTRACT

OBJECTIVE: To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. METHODS: A retrospective analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI>18 months. No cases of acute G3 toxicity or greater occurred. CONCLUSIONS: SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.


Subject(s)
Adenocarcinoma/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Pancreatectomy , Pancreatic Neoplasms/radiotherapy , Pancreaticoduodenectomy , Radiosurgery , Adenocarcinoma/diagnostic imaging , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , Tomography, X-Ray Computed
3.
Technol Cancer Res Treat ; 16(3): 295-301, 2017 06.
Article in English | MEDLINE | ID: mdl-27311310

ABSTRACT

PURPOSE: To assess the efficacy of stereotactic body radiotherapy in patients with unresectable locally advanced pancreatic cancer. MATERIALS AND METHODS: All patients received a prescription dose of 45 Gy in 6 fractions. Primary end point was freedom from local progression. Secondary end points were overall survival, progression-free survival, and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. RESULTS: Forty-five patients were enrolled in a phase 2 trial. Median follow-up was 13.5 months. Freedom from local progression was 90% at 2 years. On univariate ( P < .03) and multivariate analyses ( P < .001), lesion size was statistically significant for freedom from local progression. Median progression-free survival and overall survival were 8 and 13 months, respectively. On multivariate analysis, tumor size ( P < .001) and freedom from local progression ( P < .002) were significantly correlated with overall survival. Thirty-two (71%) patients with locally advanced pancreatic cancer received chemotherapy before stereotactic body radiotherapy. Median overall survival from diagnosis was 19 months. Multivariate analysis showed that freedom from local progression ( P < .035), tumor diameter ( P < .002), and computed tomography before stereotactic body radiotherapy ( P < .001) were significantly correlated with overall survival from diagnosis. CONCLUSION: Stereotactic body radiotherapy is a safe and effective treatment for patients with locally advanced pancreatic cancer with no G3 toxicity or greater and could be a promising therapeutic option in multimodality treatment regimen.


Subject(s)
Adenocarcinoma/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Pancreatic Neoplasms/radiotherapy , Radiosurgery/methods , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Deoxycytidine/administration & dosage , Disease Progression , Disease-Free Survival , Dose Fractionation, Radiation , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms
4.
Ann Oncol ; 26(3): 542-7, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25538178

ABSTRACT

BACKGROUND: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. PATIENTS AND METHODS: Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. RESULTS: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). CONCLUSIONS: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. CLINICAL TRIAL NUMBER: NCT00753675.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Piperidines/administration & dosage , Quinazolines/administration & dosage , Aged , Deoxycytidine/administration & dosage , Double-Blind Method , Female , Humans , Male , Middle Aged , Gemcitabine
5.
Br J Cancer ; 103(6): 837-44, 2010 Sep 07.
Article in English | MEDLINE | ID: mdl-20717115

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. METHODS: Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 microg m(-2) once every 3 weeks. The primary aim of the study was progression-free survival (PFS). RESULTS: No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months. CONCLUSION: NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Oligopeptides/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use , Adult , Aged , Carcinoma, Hepatocellular/blood supply , Female , Humans , Liver Neoplasms/blood supply , Male , Middle Aged , Oligopeptides/adverse effects , Tumor Necrosis Factor-alpha/adverse effects
6.
Ann Oncol ; 19(3): 508-15, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17998284

ABSTRACT

BACKGROUND: KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer (mCRC) treated with cetuximab (CTX). PATIENTS AND METHODS: We studied the KRAS mutation status of 113 patients with irinotecan refractory mCRC treated with CTX in clinical trials. A predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed using logistic and Cox regression. RESULTS: OR was seen in 27 of 66 KRAS wild-type (WT) patients versus 0 of 42 in KRAS mutants. Median OS was significantly better in KRAS WT versus mutants (43.0 versus 27.3 weeks; P = 0.020). Decrease in tumor sizes was significantly larger at all time points in WT patients. KRAS WT patients with an initial relative decrease of tumor size >9.66% at week 6 had a significantly better median OS compared with all other patients (74.9 versus 30.6 weeks; P = 0.0000025). Within KRAS WT patients OS was significantly better in patients with an initial decrease compared with those without [median OS: 74.9 versus 30.6 weeks (P = 0.00000012)]. CONCLUSIONS: KRAS WT status is associated to survival benefit in CTX treated mCRC. This benefit is even more pronounced in those patients with early radiological response. These characteristics may be exploited for response prediction.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Mutation , Proto-Oncogene Proteins/analysis , ras Proteins/analysis , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cetuximab , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Humans , Irinotecan , Logistic Models , Male , Middle Aged , Proportional Hazards Models , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Sensitivity and Specificity , Survival Rate , Tomography, X-Ray Computed
7.
Acta Gastroenterol Belg ; 69(1): 55-8, 2006.
Article in English | MEDLINE | ID: mdl-16673565

ABSTRACT

Colorectal cancer is a severe disease with a significant incidence in Western world. In the course of disease, about 40% of patients will eventually develop metastases to the liver. The majority of them will never be candidate for curative surgical management. For those patients, systemic or intra-hepatic chemotherapy is the treatment's cornerstone. Unfortunately, despite evident improvements and apparition of several active new agents, no hope of cure emerges on the agenda for now. Hepatic intra-arterial injections of radioactive devices have since a long time drawn interest from the medical community. An anti-tumoural activity has been demonstrated with Yttrium-loaded microspheres injected in the hepatic artery for several liver neoplasms including metastases from colorectal cancer. We lack however the results of large randomized phase III trials to define clearly the place of those interventional therapies in the management of colorectal cancer metastatic to the liver.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Yttrium Isotopes/administration & dosage , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Female , Follow-Up Studies , Hepatic Artery , Humans , Injections, Intra-Arterial , Liver Neoplasms/pathology , Male , Microspheres , Neoplasm Staging , Risk Assessment , Survival Analysis , Treatment Outcome
8.
Eur J Immunol ; 31(10): 3016-25, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11592078

ABSTRACT

The Her2/neu (c-erbB-2) oncogene encodes a 185-kDa protein tyrosine kinase which is overexpressed in 20% of breast adenocarcinomas and is recognized by a humanized anti-Her2/neu monoclonal antibody (mAb) (rhu4D5 or Herceptin). Natural killer (NK) cells are capable of mediating antibody-dependent cell cytotoxicity (ADCC) against antibody-coated targets via their expression of a low-affinity receptor for IgG (FcgammaRIII or CD16). NK cells can be expanded in cancer patients via the administration of low-dose interleukin-2 (IL-2) and become potent cytotoxic effectors following exposure to high doses of IL-2. We tested IL-2-activated NK cells against Her2/neu+ (MCF-7Her2/neu) and Her2/neu- (MDA-468) breast cancer cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence or absence of rhu4D5 mAb (effector : target ratio = 10 : 1). Specific lysis of rhu4D5-coated MCF-7Her2/neu and MDA-468 target cells by IL-2-activated NK cells was 35% and 3%, respectively (p < 0.05). Lysis was less than 5% when targets were treated with either the non-humanized mu4D5 mAb or control huIgG. Lysis of rhu4D5-coated MCF-7Her2/neu cells was inhibited by 80 % when NK cells were pre-treated with an anti-Fc receptor antibody prior to use in the cytotoxicity assay. Enhanced ADCC of MCF-7Her2/neu target cells was seen when the effector cells consisted of mononuclear cells obtained from a patient demonstrating significant expansion of NK cells secondary to therapy with low-dose IL-2. Serum from patients receiving infusions of rhu4D5 mAb could substitute for exogenous antibody in the ADCC assay. NK cells activated by rhu4D5-coated tumor cells in the presence of IL-2 also produced large amounts of IFN-gamma with concomitant up-regulation of cell-surface activation markers CD25 and CD69. These results lend support to the concurrent use of rhu4D5 mAb and IL-2 therapy in patients with cancers that express the Her2/neu oncogene.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Breast Neoplasms/therapy , Interleukin-2/pharmacology , Killer Cells, Natural/immunology , Animals , Antibodies, Monoclonal, Humanized , Antibody-Dependent Cell Cytotoxicity , Breast Neoplasms/immunology , Breast Neoplasms/pathology , CD56 Antigen/analysis , Cytokines/biosynthesis , Humans , Killer Cells, Natural/drug effects , Lymphocyte Activation , Mice , Receptor, ErbB-2/analysis , Receptors, IgG/physiology , Trastuzumab , Tumor Cells, Cultured
SELECTION OF CITATIONS
SEARCH DETAIL
...