Giuseppe Badalamenti - Academia.edu (original) (raw)

Papers by Giuseppe Badalamenti

Research paper thumbnail of A case of squamocellular uterine cervix carcinoma metastatic to the skin with enterocutaneous fistula

Tumori

Metastases to the skin complicated by enterocutaneous fistula are a rare event in gynecological m... more Metastases to the skin complicated by enterocutaneous fistula are a rare event in gynecological malignancies. We present the case of a 70-year-old woman with uterine cervix carcinoma metastatic to the skin and treated with surgery and radiotherapy. The last relapse to the skin was complicated by the formation of an enterocutaneous fistula. This low-output fistula was treated with surgery and adequate supportive care. The treatment of enterocutaneous fistulas may be either invasive (surgical resection, surgical repair with corrective procedures or with myocutaneous flaps, colonic and/or urinary diversion, endoscopic treatments with metallic stents) or conservative (skin care and local disinfection, pouching of secretions, control of nutrition and electrolytes, TPN, antisecretory treatment with scopolamine or octreotide, and control of psychological conditions). Enterocutaneous fistulas associated with skin metastases are not commonly reported in the literature and may be successfully...

Research paper thumbnail of Lenograstim in preventing chemotherapy-induced febrile neutropenia in patients with soft tissue sarcoma

Anticancer research, 2013

Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in... more Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in chemotherapeutic regimens for soft tissue sarcoma. Prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN). The correct timing of G-CSF administration should be considered in order to optimize the prophylactic treatment. Patients (≥18 years old) affected by soft tissue sarcoma and treated with epirubicin and ifosfamide, underwent prophylactic treatment with G-CSF (lenograstim at 263 μg) from day 5 to day 9. The proportion of patients experiencing FN and G4 neutropenia was considered. A total of 36 patients receiving three cycles of chemotherapy with epirubicin plus ifosfamide were treated. None developed FN; G4 neutropenia was reported in 17% of patients. No treatment delay or dose reduction was required, no antibiotic therapy was administered and no hospitalization occurred. Five-day lenograstim treatment is efficient as prophylaxis of FN...

Research paper thumbnail of MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone

Anticancer research

The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (... more The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 we...

Research paper thumbnail of Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases

Anticancer research

The effects of the bisphosphonate derivative zoledronic acid (ZA) on the circulating levels of ma... more The effects of the bisphosphonate derivative zoledronic acid (ZA) on the circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in patients with bone metastasis (BMTS) and the possible correlation with the symptomatic response induced by this drug in these patients were evaluated. Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the plasma of 30 patients with painful bone metastases from breast or prostate cancer undergoing multiple treatment with ZA (4 mg i.v., every 4 weeks). Healthy subjects (HS) of both genders (12 female and 30 male) served as the control group. The symptomatic response to ZA was assessed by the visual analog scale score (VAS). The median MMP-2 and MMP-9 pretreatment levels were more elevated in BMTS as compared to HS (p < or = 0.0001). Conversely, uPA levels were lower in BMTS p = 0.0033; no significant difference was...

Research paper thumbnail of Tumor markers in urogynaecological tumors

La Tunisie médicale, 2005

Research paper thumbnail of Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial

Lancet, Jan 26, 2013

Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointest... more Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were randomised in a 2:1 ratio (by computer-generated randomisation list and interactive voice response system; preallocated block design (block size 12); stratified by treatment line and geographical region) to receive either oral regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle. The study sponsor, participants, and investi...

Research paper thumbnail of Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C

Medical Oncology, 2008

The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst... more The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst C), an endogenous inhibitor of cysteine proteinase cathepsin K, was investigated by immunoassays in patients with bone metastasis from breast cancer (BCa) or prostate cancer (PCa). Additional studies were also performed in these patients to assess the effects of zoledronic acid (ZA) administration on the circulating levels of these molecules. Mean IL-6 and Cyst C serum concentrations were significantly increased in BCa patients and in patients with primary osteoporosis (PO) compared to healthy subjects (HS). However, Cyst C, but not IL-6, resulted significantly more elevated in BCa patients than in PO patients. Furthermore, in BCa patients no correlation was highlighted between IL-6 and Cyst C or between these molecules and some clinicobiological parameters of malignant progression. Mean IL-6 levels were also higher in PCa patients and in patients with benign prostatic hyperplasia (BPH) than in HS while Cyst C resulted significantly higher in PCa but not in BPH patients as compared to HS. In PCa patients, a positive correlation was highlighted between IL-6 and number of bone metastases or serum prostate-specific antigen but not with the Gleason score. Conversely, Cyst C levels did not correlate with any of the parameters considered above or with IL-6. Receiver operating characteristic (ROC) curve analysis showed a poor diagnostic accuracy of IL-6 and Cyst C to detect BCa patients with skeletal metastases while, in PCa patients, only IL-6 showed a fair diagnostic performance in this respect. Finally, the administration of ZA to patients with bone metastases induced a statistically significant increase of serum IL-6 and Cyst C only PCa patients with bone metastasis. These data indicate that IL-6 and Cyst C may be regarded as novel targets for cancer treatment and as markers of increased osteoblastic activity associated to bisphosphonate treatments in PCa patients with bone metastases.

Research paper thumbnail of Antiblastic Drug Combinations with Ifosfamide: An Update

Antiblastic Drug Combinations with Ifosfamide: An Update

Oncology, 2003

Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such... more Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such as sarcomas, lymphomas, pediatric malignancies, germ cell tumors, lung, breast and ovarian cancer. The clinical toxicity of ifosfamide depends on the dose and administration schedules. The pharmacologic features of this drug enable its combination with other antiblastic agents, such as vinorelbine, gemcitabine, paclitaxel and docetaxel. Moreover, the pharmacologic profile of ifosfamide allows the use of this antiblastic drug in patients who have previously failed many other treatments, and a large percentage of responses has already been obtained. There is some concern about the optimal scheduling of the drug with other novel chemotherapeutics. Clinical trials that include pharmacokinetic and pharmacodynamic studies may be the most efficient way to optimize the therapeutic efficacy of ifosfamide and define the dosing and scheduling.

Research paper thumbnail of Surgical treatment of extravasation injuries

Journal of Surgical Oncology, 2005

The authors present their experience of treating anti-cancer drug extravasation by means of a com... more The authors present their experience of treating anti-cancer drug extravasation by means of a composite surgical technique that consists of infiltration with physiological solution and hyaluronidase and subsequent manual aspiration of solutes alternated with profuse irrigation of the infiltrated area. In the immediate post-op we carry out a medical therapy that consists of calciparine and topic antibiotic and/or steroid creams.

Research paper thumbnail of The Use of Zoledronic Acid in Patients with Bone Metastases from Prostate Carcinoma: Effect on Analgesic Response and Bone Metabolism Biomarkers

Journal of Chemotherapy, 2005

Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metast... more Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers.

Research paper thumbnail of A Case of Guillain-Barré Syndrome in a Patient with Non Small Cell Lung Cancer Treated with Chemotherapy

A Case of Guillain-Barré Syndrome in a Patient with Non Small Cell Lung Cancer Treated with Chemotherapy

Journal of Chemotherapy, 2006

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenes... more Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenesis characterized by rapidly progressive symmetric paralysis. In the literature some cases of GBS associated with anticancer chemotherapy are reported. We present a case of a 55-year old woman who complained of progressive motor deficit in four limbs, areflexia in lower limbs and facial nerve paralysis one week after beginning cisplatin-gemcitabine chemotherapy for metastatic lung cancer. The cerebrospinal fluid analysis showed a strong positive Pandy reaction with 435 mg/dl total protein. The electromyography and the electroneuronography established the diagnosis of inflammatory demyelinating polyneuropathy. Specific therapy with intravenous immunoglobulin 25 g/day in 5 administrations for 5 days was started with complete benefit.

Research paper thumbnail of PML down-regulation in soft tissue sarcomas

Journal of Cellular Physiology, 2010

To date, little is known concerning the promyelocytic leukemia gene (PML) status in tumors of dif... more To date, little is known concerning the promyelocytic leukemia gene (PML) status in tumors of different origin, and its expression has never been evaluated in soft tissue sarcoma. The aim of the present study is focused on the identification of differences in terms of PML protein expression between different types of soft tissue sarcoma and the corresponding normal surrounding tissue. PML protein expression has been assessed by immunohistochemistry in six different histologic types of soft tissue sarcoma (synovial sarcoma, myofibroblastic sarcoma, angiosarcoma, liposarcoma, pleomorphic sarcoma, and leiomyosarcoma) and in the corresponding normal surrounding tissue. PML resulted significantly down-regulated in synovial sarcoma and in myofibroblastic sarcoma specimens. Also in angiosarcoma samples a significative difference in PML expression in comparison with normal specimens has been detected. Interestingly PML protein detection showed a different pattern of expression in the three liposarcoma histology types compared with corresponding nontumoral tissues. In particular PML protein resulted significantly down-regulated in myxoid liposarcoma and in dedifferentiated liposarcoma. On the contrary no statistically significant difference was observed in pleomorphic liposarcoma compared to normal tissue specimens. Further investigations are needed to confirm these data and to assess the possible value of PML expression as a prognostic factor in these extremely aggressive diseases.

Research paper thumbnail of A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma

International Journal of Gynecological Cancer, 2006

Valerio MR, N. A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphami... more Valerio MR, N. A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma. Int J Gynecol Cancer 2006;16(Suppl. 1):79-85

Research paper thumbnail of Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study

Endocrine Related Cancer, 2010

Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line sys... more Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line systemic treatments in advanced disease include mitotane, either alone or in combination with chemotherapy. Studies evaluating second-line therapy options have obtained disappointing results. This trial assessed the activity and toxicity of gemcitabine plus metronomic fluoropyrimidines in heavily pretreated advanced ACC patients. From 1998 to 2008, 28 patients with advanced ACC progressing after mitotane plus one or two systemic chemotherapy lines were enrolled. They received a combination of i.v. gemcitabine (800 mg/m 2 , on days 1 and 8, every 21 days) and i.v. 5-fluorouracil protracted infusion (200 mg/m 2 /daily without interruption until progression) in the first six patients, or oral capecitabine (1500 mg/daily) in the subsequent patients. Mitotane administration was maintained in all cases. The rate of non-progressing patients after 4 months of treatment was 46.3%. A complete response was observed in 1 patient (3.5%); 1 patient (3.5%) obtained a partial regression, 11 patients (39.3%) obtained a disease stabilization and 15 patients (53.7%) progressed. Treatment was well tolerated, with grade III and IV toxicities consisting of leukopenia in six patients (21.4%), thrombocytopenia in one patient (3.5%), and mucositis in one patient (3.5%). Median time to progression and overall survival in the patient population were 5.3 (range: 1-43) and 9.8 months (range: 3-73) respectively. Gemcitabine plus metronomic fluoropyrimidines is a well-tolerated and moderately active regimen in heavily pretreated ACC patients.

Research paper thumbnail of Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Clinical & Experimental Metastasis, 2006

Recent studies have highlighted that Activin A, a member of the transforming growth factor-b (TGF... more Recent studies have highlighted that Activin A, a member of the transforming growth factor-b (TGF-b) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzymelinked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM-patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM-patients (BC: AUC = 0.71 ± 0.09, P = 0.03; PC: AUC = 0.73 ± 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease.

Research paper thumbnail of Serum follistatin in patients with prostate cancer metastatic to the bone

Clinical & Experimental Metastasis, 2010

The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional ... more The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional cytokine activin A (Act A), was investigated in patients with prostate cancer (PCa). The serum concentrations of this molecule were determined by an enzyme-linked immunosorbent assay (ELISA) in PCa patients with (M?) or without (M0) bone metastases, in patients with benign prostate hyperplasia (BPH) and in healthy subjects (HS). The effectiveness of FLST in detecting PCa patients with skeletal metastases was determined by the receiver operating characteristic (ROC) curve analysis. Serum FLST was significantly higher in PCa patients than in BPH patients (P = 0.001) or HS (P = 0.011). Conversely, in BPH patients, FLST levels resulted lower than in HS (P = 0.025). In cancer patients the serum concentrations of FLST significantly correlated with the presence of bone metastases (P = 0.0005) or increased PSA levels (P = 0.04). Interestingly, significant differences in the ratio between FLST and Act A serum concentrations (FLST/Act A) were observed between HS and BPH patients (P = 0.001) or PCa patients (P = 0.0005). Finally, ROC curve analysis, highlighted a sound diagnostic performance of FLST in detecting M? patients (P = 0.0001). However, the diagnostic effectiveness of FLST did not result significantly superior to that of Act A or PSA. These findings suggest that FLST may be regarded as a potential, molecular target in the treatment of metastatic bone disease while its clinical role as soluble marker in the clinical management of PCa patients with bone metastases needs to be better defined.

Research paper thumbnail of A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

Breast Cancer Research and Treatment, 2006

A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were s... more A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s brother and her two sons. Direct automatic sequencing of DNA extracted from the lymphocytes showed exactly the same 4843delC frameshift mutation only in the brother. In conclusion, the characterization of this mutation could help in the identification of a founder mutation of sicilian area and this may provide significant advantages for genetic counselling.

Research paper thumbnail of Efficacy of zoledronic acid in patients with colorectal cancer metastatic to bone

Bone, 2011

Purpose: Androgen deprivation therapy (ADT) is associated with loss of bone mineral density (BMD)... more Purpose: Androgen deprivation therapy (ADT) is associated with loss of bone mineral density (BMD). Preexisting bone losses in men with prostate cancer are of great concern because of accelerated bone loss during ADT. We sought to identify the risk factors associated with osteoporosis in Korean patients with prostate cancer who had not received ADT. Materials and methods: Patients who underwent biopsy of the prostate because of a high prostate-specific antigen (PSA) level or a palpable nodule in a digital rectal examination were included in this study. The patients (n = 90) were divided into 2 major groups according to biopsy results: the prostate cancer group (group 1, n = 41) and non-prostate cancer group (group 2, n = 49). The age, body mass index (BMI), lifestyle, testosterone concentration, BMD, and disease variables in prostate cancer were obtained and analyzed prospectively. BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Results: In group 1, 41.4% had osteopenia (36.6%) or osteoporosis (4.8%); in group 2, 26.5% had osteopenia (22.4%) or osteoporosis (4.1%). The estimated mean T-score was significantly (p = 0.037) lower in group 1 (−0.668 ± 1.364) than in group 2 (−0.041 ± 1.426). The significant factors correlated with BMD (T-score) in prostate cancer were age (p = 0.012), serum testosterone level (p = 0.019), and BMI (p = 0.004). Conclusions: BMDs were lower in men with prostate cancer who had not received ADT than in the control group. Consideration should be given to counseling on risk factors and lifestyle issues in prostate cancer patients with old age, low serum testosterone, and slender stature before initiating ADT.

Research paper thumbnail of Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers

Annals of Oncology, 2006

Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients pre... more Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients.

Research paper thumbnail of 4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily)

Annals of Oncology, 2007

Background: The frequency and the type of BRCA1 mutations vary widely and might have different ge... more Background: The frequency and the type of BRCA1 mutations vary widely and might have different geographic and ethnic distribution. Most of these alterations are generally found in isolated populations as a consequence of the founder effect. The object of this study was to determine whether 4843delC, a deleterious mutation of the BRCA1 gene, might be due to a founder effect originating in the Sicilian region of Italy. This mutation was described by us for the first time and identified in two unrelated Sicilian families with hereditary breast/ovarian cancer. The two families were from the same geographical area (south-western area of Palermo, Sicily). The homogeneity of the ethnic group of the two families and the Single Nucleotide Polymorphism (SNPs) analysis of probands led us to perform a study of the allelotype of the various members.

Research paper thumbnail of A case of squamocellular uterine cervix carcinoma metastatic to the skin with enterocutaneous fistula

Tumori

Metastases to the skin complicated by enterocutaneous fistula are a rare event in gynecological m... more Metastases to the skin complicated by enterocutaneous fistula are a rare event in gynecological malignancies. We present the case of a 70-year-old woman with uterine cervix carcinoma metastatic to the skin and treated with surgery and radiotherapy. The last relapse to the skin was complicated by the formation of an enterocutaneous fistula. This low-output fistula was treated with surgery and adequate supportive care. The treatment of enterocutaneous fistulas may be either invasive (surgical resection, surgical repair with corrective procedures or with myocutaneous flaps, colonic and/or urinary diversion, endoscopic treatments with metallic stents) or conservative (skin care and local disinfection, pouching of secretions, control of nutrition and electrolytes, TPN, antisecretory treatment with scopolamine or octreotide, and control of psychological conditions). Enterocutaneous fistulas associated with skin metastases are not commonly reported in the literature and may be successfully...

Research paper thumbnail of Lenograstim in preventing chemotherapy-induced febrile neutropenia in patients with soft tissue sarcoma

Anticancer research, 2013

Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in... more Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in chemotherapeutic regimens for soft tissue sarcoma. Prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN). The correct timing of G-CSF administration should be considered in order to optimize the prophylactic treatment. Patients (≥18 years old) affected by soft tissue sarcoma and treated with epirubicin and ifosfamide, underwent prophylactic treatment with G-CSF (lenograstim at 263 μg) from day 5 to day 9. The proportion of patients experiencing FN and G4 neutropenia was considered. A total of 36 patients receiving three cycles of chemotherapy with epirubicin plus ifosfamide were treated. None developed FN; G4 neutropenia was reported in 17% of patients. No treatment delay or dose reduction was required, no antibiotic therapy was administered and no hospitalization occurred. Five-day lenograstim treatment is efficient as prophylaxis of FN...

Research paper thumbnail of MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone

Anticancer research

The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (... more The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 we...

Research paper thumbnail of Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases

Anticancer research

The effects of the bisphosphonate derivative zoledronic acid (ZA) on the circulating levels of ma... more The effects of the bisphosphonate derivative zoledronic acid (ZA) on the circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in patients with bone metastasis (BMTS) and the possible correlation with the symptomatic response induced by this drug in these patients were evaluated. Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the plasma of 30 patients with painful bone metastases from breast or prostate cancer undergoing multiple treatment with ZA (4 mg i.v., every 4 weeks). Healthy subjects (HS) of both genders (12 female and 30 male) served as the control group. The symptomatic response to ZA was assessed by the visual analog scale score (VAS). The median MMP-2 and MMP-9 pretreatment levels were more elevated in BMTS as compared to HS (p < or = 0.0001). Conversely, uPA levels were lower in BMTS p = 0.0033; no significant difference was...

Research paper thumbnail of Tumor markers in urogynaecological tumors

La Tunisie médicale, 2005

Research paper thumbnail of Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial

Lancet, Jan 26, 2013

Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointest... more Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were randomised in a 2:1 ratio (by computer-generated randomisation list and interactive voice response system; preallocated block design (block size 12); stratified by treatment line and geographical region) to receive either oral regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle. The study sponsor, participants, and investi...

Research paper thumbnail of Serum interleukin-6 in patients with metastatic bone disease: correlation with cystatin C

Medical Oncology, 2008

The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst... more The clinical significance of serum interleukin-6 (IL-6) and its correlation with cystatin C (Cyst C), an endogenous inhibitor of cysteine proteinase cathepsin K, was investigated by immunoassays in patients with bone metastasis from breast cancer (BCa) or prostate cancer (PCa). Additional studies were also performed in these patients to assess the effects of zoledronic acid (ZA) administration on the circulating levels of these molecules. Mean IL-6 and Cyst C serum concentrations were significantly increased in BCa patients and in patients with primary osteoporosis (PO) compared to healthy subjects (HS). However, Cyst C, but not IL-6, resulted significantly more elevated in BCa patients than in PO patients. Furthermore, in BCa patients no correlation was highlighted between IL-6 and Cyst C or between these molecules and some clinicobiological parameters of malignant progression. Mean IL-6 levels were also higher in PCa patients and in patients with benign prostatic hyperplasia (BPH) than in HS while Cyst C resulted significantly higher in PCa but not in BPH patients as compared to HS. In PCa patients, a positive correlation was highlighted between IL-6 and number of bone metastases or serum prostate-specific antigen but not with the Gleason score. Conversely, Cyst C levels did not correlate with any of the parameters considered above or with IL-6. Receiver operating characteristic (ROC) curve analysis showed a poor diagnostic accuracy of IL-6 and Cyst C to detect BCa patients with skeletal metastases while, in PCa patients, only IL-6 showed a fair diagnostic performance in this respect. Finally, the administration of ZA to patients with bone metastases induced a statistically significant increase of serum IL-6 and Cyst C only PCa patients with bone metastasis. These data indicate that IL-6 and Cyst C may be regarded as novel targets for cancer treatment and as markers of increased osteoblastic activity associated to bisphosphonate treatments in PCa patients with bone metastases.

Research paper thumbnail of Antiblastic Drug Combinations with Ifosfamide: An Update

Antiblastic Drug Combinations with Ifosfamide: An Update

Oncology, 2003

Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such... more Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such as sarcomas, lymphomas, pediatric malignancies, germ cell tumors, lung, breast and ovarian cancer. The clinical toxicity of ifosfamide depends on the dose and administration schedules. The pharmacologic features of this drug enable its combination with other antiblastic agents, such as vinorelbine, gemcitabine, paclitaxel and docetaxel. Moreover, the pharmacologic profile of ifosfamide allows the use of this antiblastic drug in patients who have previously failed many other treatments, and a large percentage of responses has already been obtained. There is some concern about the optimal scheduling of the drug with other novel chemotherapeutics. Clinical trials that include pharmacokinetic and pharmacodynamic studies may be the most efficient way to optimize the therapeutic efficacy of ifosfamide and define the dosing and scheduling.

Research paper thumbnail of Surgical treatment of extravasation injuries

Journal of Surgical Oncology, 2005

The authors present their experience of treating anti-cancer drug extravasation by means of a com... more The authors present their experience of treating anti-cancer drug extravasation by means of a composite surgical technique that consists of infiltration with physiological solution and hyaluronidase and subsequent manual aspiration of solutes alternated with profuse irrigation of the infiltrated area. In the immediate post-op we carry out a medical therapy that consists of calciparine and topic antibiotic and/or steroid creams.

Research paper thumbnail of The Use of Zoledronic Acid in Patients with Bone Metastases from Prostate Carcinoma: Effect on Analgesic Response and Bone Metabolism Biomarkers

Journal of Chemotherapy, 2005

Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metast... more Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers.

Research paper thumbnail of A Case of Guillain-Barré Syndrome in a Patient with Non Small Cell Lung Cancer Treated with Chemotherapy

A Case of Guillain-Barré Syndrome in a Patient with Non Small Cell Lung Cancer Treated with Chemotherapy

Journal of Chemotherapy, 2006

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenes... more Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenesis characterized by rapidly progressive symmetric paralysis. In the literature some cases of GBS associated with anticancer chemotherapy are reported. We present a case of a 55-year old woman who complained of progressive motor deficit in four limbs, areflexia in lower limbs and facial nerve paralysis one week after beginning cisplatin-gemcitabine chemotherapy for metastatic lung cancer. The cerebrospinal fluid analysis showed a strong positive Pandy reaction with 435 mg/dl total protein. The electromyography and the electroneuronography established the diagnosis of inflammatory demyelinating polyneuropathy. Specific therapy with intravenous immunoglobulin 25 g/day in 5 administrations for 5 days was started with complete benefit.

Research paper thumbnail of PML down-regulation in soft tissue sarcomas

Journal of Cellular Physiology, 2010

To date, little is known concerning the promyelocytic leukemia gene (PML) status in tumors of dif... more To date, little is known concerning the promyelocytic leukemia gene (PML) status in tumors of different origin, and its expression has never been evaluated in soft tissue sarcoma. The aim of the present study is focused on the identification of differences in terms of PML protein expression between different types of soft tissue sarcoma and the corresponding normal surrounding tissue. PML protein expression has been assessed by immunohistochemistry in six different histologic types of soft tissue sarcoma (synovial sarcoma, myofibroblastic sarcoma, angiosarcoma, liposarcoma, pleomorphic sarcoma, and leiomyosarcoma) and in the corresponding normal surrounding tissue. PML resulted significantly down-regulated in synovial sarcoma and in myofibroblastic sarcoma specimens. Also in angiosarcoma samples a significative difference in PML expression in comparison with normal specimens has been detected. Interestingly PML protein detection showed a different pattern of expression in the three liposarcoma histology types compared with corresponding nontumoral tissues. In particular PML protein resulted significantly down-regulated in myxoid liposarcoma and in dedifferentiated liposarcoma. On the contrary no statistically significant difference was observed in pleomorphic liposarcoma compared to normal tissue specimens. Further investigations are needed to confirm these data and to assess the possible value of PML expression as a prognostic factor in these extremely aggressive diseases.

Research paper thumbnail of A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma

International Journal of Gynecological Cancer, 2006

Valerio MR, N. A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphami... more Valerio MR, N. A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma. Int J Gynecol Cancer 2006;16(Suppl. 1):79-85

Research paper thumbnail of Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study

Endocrine Related Cancer, 2010

Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line sys... more Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line systemic treatments in advanced disease include mitotane, either alone or in combination with chemotherapy. Studies evaluating second-line therapy options have obtained disappointing results. This trial assessed the activity and toxicity of gemcitabine plus metronomic fluoropyrimidines in heavily pretreated advanced ACC patients. From 1998 to 2008, 28 patients with advanced ACC progressing after mitotane plus one or two systemic chemotherapy lines were enrolled. They received a combination of i.v. gemcitabine (800 mg/m 2 , on days 1 and 8, every 21 days) and i.v. 5-fluorouracil protracted infusion (200 mg/m 2 /daily without interruption until progression) in the first six patients, or oral capecitabine (1500 mg/daily) in the subsequent patients. Mitotane administration was maintained in all cases. The rate of non-progressing patients after 4 months of treatment was 46.3%. A complete response was observed in 1 patient (3.5%); 1 patient (3.5%) obtained a partial regression, 11 patients (39.3%) obtained a disease stabilization and 15 patients (53.7%) progressed. Treatment was well tolerated, with grade III and IV toxicities consisting of leukopenia in six patients (21.4%), thrombocytopenia in one patient (3.5%), and mucositis in one patient (3.5%). Median time to progression and overall survival in the patient population were 5.3 (range: 1-43) and 9.8 months (range: 3-73) respectively. Gemcitabine plus metronomic fluoropyrimidines is a well-tolerated and moderately active regimen in heavily pretreated ACC patients.

Research paper thumbnail of Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Clinical & Experimental Metastasis, 2006

Recent studies have highlighted that Activin A, a member of the transforming growth factor-b (TGF... more Recent studies have highlighted that Activin A, a member of the transforming growth factor-b (TGF-b) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzymelinked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM-) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM-patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM-patients (BC: AUC = 0.71 ± 0.09, P = 0.03; PC: AUC = 0.73 ± 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease.

Research paper thumbnail of Serum follistatin in patients with prostate cancer metastatic to the bone

Clinical & Experimental Metastasis, 2010

The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional ... more The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional cytokine activin A (Act A), was investigated in patients with prostate cancer (PCa). The serum concentrations of this molecule were determined by an enzyme-linked immunosorbent assay (ELISA) in PCa patients with (M?) or without (M0) bone metastases, in patients with benign prostate hyperplasia (BPH) and in healthy subjects (HS). The effectiveness of FLST in detecting PCa patients with skeletal metastases was determined by the receiver operating characteristic (ROC) curve analysis. Serum FLST was significantly higher in PCa patients than in BPH patients (P = 0.001) or HS (P = 0.011). Conversely, in BPH patients, FLST levels resulted lower than in HS (P = 0.025). In cancer patients the serum concentrations of FLST significantly correlated with the presence of bone metastases (P = 0.0005) or increased PSA levels (P = 0.04). Interestingly, significant differences in the ratio between FLST and Act A serum concentrations (FLST/Act A) were observed between HS and BPH patients (P = 0.001) or PCa patients (P = 0.0005). Finally, ROC curve analysis, highlighted a sound diagnostic performance of FLST in detecting M? patients (P = 0.0001). However, the diagnostic effectiveness of FLST did not result significantly superior to that of Act A or PSA. These findings suggest that FLST may be regarded as a potential, molecular target in the treatment of metastatic bone disease while its clinical role as soluble marker in the clinical management of PCa patients with bone metastases needs to be better defined.

Research paper thumbnail of A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

Breast Cancer Research and Treatment, 2006

A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were s... more A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s brother and her two sons. Direct automatic sequencing of DNA extracted from the lymphocytes showed exactly the same 4843delC frameshift mutation only in the brother. In conclusion, the characterization of this mutation could help in the identification of a founder mutation of sicilian area and this may provide significant advantages for genetic counselling.

Research paper thumbnail of Efficacy of zoledronic acid in patients with colorectal cancer metastatic to bone

Bone, 2011

Purpose: Androgen deprivation therapy (ADT) is associated with loss of bone mineral density (BMD)... more Purpose: Androgen deprivation therapy (ADT) is associated with loss of bone mineral density (BMD). Preexisting bone losses in men with prostate cancer are of great concern because of accelerated bone loss during ADT. We sought to identify the risk factors associated with osteoporosis in Korean patients with prostate cancer who had not received ADT. Materials and methods: Patients who underwent biopsy of the prostate because of a high prostate-specific antigen (PSA) level or a palpable nodule in a digital rectal examination were included in this study. The patients (n = 90) were divided into 2 major groups according to biopsy results: the prostate cancer group (group 1, n = 41) and non-prostate cancer group (group 2, n = 49). The age, body mass index (BMI), lifestyle, testosterone concentration, BMD, and disease variables in prostate cancer were obtained and analyzed prospectively. BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Results: In group 1, 41.4% had osteopenia (36.6%) or osteoporosis (4.8%); in group 2, 26.5% had osteopenia (22.4%) or osteoporosis (4.1%). The estimated mean T-score was significantly (p = 0.037) lower in group 1 (−0.668 ± 1.364) than in group 2 (−0.041 ± 1.426). The significant factors correlated with BMD (T-score) in prostate cancer were age (p = 0.012), serum testosterone level (p = 0.019), and BMI (p = 0.004). Conclusions: BMDs were lower in men with prostate cancer who had not received ADT than in the control group. Consideration should be given to counseling on risk factors and lifestyle issues in prostate cancer patients with old age, low serum testosterone, and slender stature before initiating ADT.

Research paper thumbnail of Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers

Annals of Oncology, 2006

Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients pre... more Background: Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients.

Research paper thumbnail of 4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily)

Annals of Oncology, 2007

Background: The frequency and the type of BRCA1 mutations vary widely and might have different ge... more Background: The frequency and the type of BRCA1 mutations vary widely and might have different geographic and ethnic distribution. Most of these alterations are generally found in isolated populations as a consequence of the founder effect. The object of this study was to determine whether 4843delC, a deleterious mutation of the BRCA1 gene, might be due to a founder effect originating in the Sicilian region of Italy. This mutation was described by us for the first time and identified in two unrelated Sicilian families with hereditary breast/ovarian cancer. The two families were from the same geographical area (south-western area of Palermo, Sicily). The homogeneity of the ethnic group of the two families and the Single Nucleotide Polymorphism (SNPs) analysis of probands led us to perform a study of the allelotype of the various members.