-
British Journal of Cancer 07/2009; 101(4):734-5; author reply 736-7. · 5.04 Impact Factor
-
Digestive and Liver Disease - DIG LIVER DIS. 01/2008; 40.
-
Annals of Oncology 11/2006; 17(10):1606-7. · 6.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Angiosarcomas are rare soft tissue malignancies. Typically they originate from the skin of the scalp or face, whereas visceral sarcomas are very rare. We report the case of a 67-year-old man affected by a large angiosarcoma of the kidney. After surgical removal, a rapid peritoneal, visceral and cutaneous diffusion developed. Palliative chemotherapy, based on anthracycline and ifosfamide, which are normally used to treat all other high-grade spindle cell sarcomas, was totally inactive. On the basis of these results and of the biological characteristics of these rare neoplasms it is mandatory to develop other therapeutic approaches. Antiangiogenetic agents are of interest for this disease due to the peculiar origin of the cells of these sarcomas.
Journal of chemotherapy (Florence, Italy) 05/2006; 18(2):221-4. · 1.08 Impact Factor
-
F Panzuto,
C Severi,
R Cannizzaro,
M Falconi,
S Angeletti,
A Pasquali,
V D Corleto,
B Annibale, A Buonadonna,
P Pederzoli,
G Delle Fave
[show abstract]
[hide abstract]
ABSTRACT: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors.
Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups.
CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non-ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p = 0.04), in NF (95% vs 75%, p = 0.02), and in pancreatic (94% vs 74%, p = 0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p = 0.04).
The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.
Journal of endocrinological investigation 02/2004; 27(1):6-11. · 1.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated.
Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111-DTPA-octreotide ((111)In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen.
SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease.
In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.
Annals of Oncology 08/2003; 14(7):1135-41. · 6.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).
Oncology 02/2003; 65 Suppl 2:80-4. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas.
We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997.
Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival.
Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival.
European Journal of Surgical Oncology 04/2002; 28(2):153-64. · 2.50 Impact Factor
-
S Frustaci,
F Gherlinzoni,
A De Paoli,
M Bonetti,
A Azzarelli,
A Comandone,
P Olmi, A Buonadonna,
G Pignatti,
E Barbieri,
G Apice,
H Zmerly,
D Serraino,
P Picci
[show abstract]
[hide abstract]
ABSTRACT: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study was designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents.
Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter > or = 5 cm or any size recurrent tumor) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor).
After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P =.04); and the median overall survival (OS) was 75 months for treated and 46 months for untreated patients (P =.03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P =.04).
Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.
Journal of Clinical Oncology 04/2001; 19(5):1238-47. · 18.37 Impact Factor
-
British Journal of Cancer 05/1999; 79(11-12):1943. · 5.04 Impact Factor
-
O Pagani,
C Sessa,
G Martinelli,
D Crivellari, A Buonadonna,
B Thürlimann,
D Hess,
M Borner,
J Bauer,
G Zampino,
M Zimatore,
R Graffeo,
A Riva,
A Goldhirsch
[show abstract]
[hide abstract]
ABSTRACT: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile.
Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with > or = 2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m2 and D 75 mg/m2 to E 120 mg/m2 and D 85 mg/m2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography.
Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) < 0.1 x 10(9)/l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m2 and D 75 mg/m2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m2 and D 75 mg/m2. The MTD with G-CSF support was established at E 120 mg/m2 and D 85 mg/m2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 x 10(9)/l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotoxicity. Antitumor activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%-75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2-30+), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months.
The combination of E and D proved to be an effective and safe regimen in poor- prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimens.
Annals of Oncology 05/1999; 10(5):539-45. · 6.43 Impact Factor
-
E. Galligioni,
G. Cetto,
O. Nascimben, A. Buonadonna,
D. Crivellari,
A. Molino,
A. Veronesi,
C. Graiff,
S. Barni,
C. Puccetti,
E. Ferrazzi,
E. Recaldin
European Journal of Cancer - EUR J CANCER. 01/1998; 34.
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the maximum-tolerated dose (MTD) of 4'-epidoxorubicin (EPI) in combination with full dose of ifosfamide (IFO) when granulocyte-macrophage colony-stimulating factor (GM-CSF) was used, to estimate its clinical efficacy, and to evaluate the mobilization of hematopoietic progenitors.
Previously untreated advanced patients were treated with fixed doses of IFO at 1.8 g/m2/d for 5 days and escalating doses of EPI. The starting dose level of EPI was 50 mg/m2 bolus on days 1 and 2; subsequent levels were 60 mg/m2 and 70 mg/ m2 given on days 1 and 2. GM-CSF (5 micrograms/kg/d) was administered from days +6 to +19. Clinical evaluation of response was performed after three consecutive cycles. Mobilization of hematopoietic progenitors was evaluated as day 14 CFU-GM after the first cycle only.
Overall, six, 18, and 13 assessable patients were entered onto each EPI dose level, respectively. The first and the second EPI level were considered feasible. Conversely, at the third level, only six of 13 patients [46%] tolerated full EPI doses at the scheduled time. Therefore, the dose-intensity of the three levels was 100%, 99.7%, and 86.1%, respectively. Overall, 20 of 37 patients (54%) obtained an objective response. The response rates for the three EPI dose levels were significantly different [17%, 33%, and 100%, respectively; test for trend, P < .001]. Considering only lung metastases, the overall response rate was 72% (20%, 66%, and 100% for the three EPI levels, respectively). The most relevant mobilization effect was obtained at the third EPI level, when both GM-CSF and IL-3 were used as in vitro-stimulating factors.
The third EPI level (70 mg/m2 on days 1 and 2) is the MTD of this program, since it was administered, without dose reduction or treatment delay, for three consecutive cycles in less than half of the patients. Nevertheless, this level proved to be interesting with regard to response rate (13 of 13 objective responses) and in mobilization of the hematopoietic progenitors.
Journal of Clinical Oncology 04/1997; 15(4):1418-26. · 18.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The fibrin sleeve of venous catheters (VC) and parietal thrombi represent frequent and dangerous side-effects of central venous catheterization (CVC), due to the risk of embolism. Reduced levels of coagulation clotting factors inhibitors (such as Antithrombin III) are known to be associated with increased thrombogenic risk. The aim of this study was to evaluate the role of Antithrombin III (AT III) deficiency as a risk factor for thrombosis in cancer patients undergoing CVC. The study groups included patients with a reduced AT III activity (< 70%, 20 consecutive patients) and with normal AT III values (> 70%, 20 randomly selected patients), requiring a VC for chemotherapy and/or total parenteral nutrition. The study protocol included evaluation of Hb, PLTs, PT (INR), aPTT, Fibrinogen and AT III at days 0, 1, 3 and 8 after CVC and upon VC removal. Peripheral and pullout phlebographies were performed in all patients on catheter withdrawal. A quantitative scale was developed to evaluate both VC and parietal thrombus degree in each catheter-containing venous segment (subclavian, innominate, superior vena cava); the sum of the mean values was defined as overall thrombus. The average VC dwelling time was similar in both groups. There were no significant differences in Hb, PLTs, PT (INR), aPTT, Fibrinogen and in the remaining parameters of the study between the two groups. The group with AT III deficiency presented a higher degree of both parietal (p < 0.05) and overall thrombus (p < 0.02). Data showed a higher severity of CVC-related thrombosis in patients with AT III deficiency than in the control group. Further studies are needed to evaluate whether the therapeutically-induced normalization of AT III levels can reduce the thrombosis degree.
Thrombosis Research 04/1995; 78(2):127-37. · 2.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the feasibility, toxicity and efficacy of the combination of (IFO) ifosfamide and epirubicin (EPI) given at conventional doses for monochemotherapy, we started a phase II study in advanced/metastatic soft tissue sarcoma patients.
Treatment consisted of: epirubicin 75 mg/m2 i.v. day 1; IFO 1.8 g/m2 days 1 to 5; MESNA 20% of the IFO dose at 4-hour intervals three times a day during IFO administration. Cycles were given every 3-4 weeks for at least three cycles.
The overall response rate for non-visceral sarcomas (51 pts) was 31% (95% confidence limits +/- 13%). Among the 13 visceral sarcomas no response was seen for the leiomyosarcomas of the gastrointestinal tract, whereas one complete and one partial remission were observed for the uterine sarcomas. The duration of response was 10 months (range 5-34+) for complete responses and 9 (range 4-42+) for partial responses. The median survival for responders is 18 months (range 2-60+) and for non-responders 10 months (range 1-33) (p < 0.004).
This combination proved to be feasible and tolerable. The overall response rate does not appear to be superior to those with other standard treatments, but it should be pointed out that our patient population was totally unselected.
Annals of Oncology 10/1993; 4(8):669-72. · 6.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A patient affected by metastatic prostatic carcinoma and hypogonadotropic hypogonadism (HH) was treated with flutamide 750 mg/day plus an LH-RH analog. After confirmation of basal castration during treatment, he continued with antiandrogens alone. Following the normalization of gonadic function and subjective mild bone flare-up, the patient resumed the initial treatment and obtained a partial response. When flutamide was interrupted because of liver toxicity, the patient showed progressive disease in the bone, which was unresponsive to both flutamide resumption and salvage hormone therapy (bicalutamide). The patient is currently receiving chemotherapy with VP16 and estramustine phosphate and is showing both serologic (PSA) and symptomatic response. The interest of this case lies in the incidental detection of HH during therapy and in the responsiveness to treatment.
Tumori 85(4):280-3. · 0.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A case of extensive bone marrow infiltration due to gastric cancer is reported. A 65-year old man with an acute episode of anemia (Hb 4.1 mg/dl) and dyspnea was admitted to the Medical Department of a general hospital. Bone marrow biopsy showed extensive paratrabecular infiltration of a poorly differentiated adenocarcinoma of gastric origin. The primary tumor in the stomach was confirmed, and the patient was referred to our Institute and treated with combination chemotherapy (FAMTX) for 6 cycles. Due to the disappearance of bone marrow infiltration, the patient was considered for curative resection of the primary gastric cancer. After 27 months the patient is alive and in clinical complete remission.
Tumori 81(1):74-6. · 0.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report a case of a 28-year-old man with angiosarcoma of the spleen and liver metastases. The aim of this paper is to underline the importance of planned splenectomy in these patients even if they have metastatic disease, and to propose an intensive chemotherapy regimen consisting of anthracyclines, ifosfamide and mesna with G-CSF support.
Tumori 87(6):439-43. · 0.86 Impact Factor
-
S Frustaci, A Buonadonna,
A Romanini,
A Comandone,
M Dalla Palma,
T Gamucci,
C Verusio,
R Lionetto,
C Dani,
P Casali,
A Santoro
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the maximum tolerated doses (MTD) of ifosfamide when given as a continuous infusion and in combination with fixed doses of bolus 4'-epidoxorubicin in advanced previously untreated adult soft tissue sarcoma patients.
Treatment consisted of epidoxorubicin, 60 mg/m2 days one and two, and ifosfamide, 1.5 g/m2 every 12 hrs as a 72-hr infusion, at the first level. Further levels of ifosfamide were defined as increments of 12 hrs of the same infusion program. G-CSF 300 microg/die was administered from days +7 to +14. Dose-limiting toxicity (DLT) was defined as: G4 leukopenia or thrombocytopenia of > or =5 days; any G3 neuro or nephrotoxicity; G4 toxicity of any kind. Patients had to complete at least 2 consecutive cycles, and MTD was defined as the level in which 20% of patients developed a DLT; 10-15 patients were entered in each level.
First level: overall, 13 patients entered, 3 were not assessable for MTD, and only one developed a DLT. Second level: 18 patients entered, 3 were not assessable for MTD. Hematologic DLT was observed in 3/15 assessable patients. Therefore, the MTD was found at the ifosfamide level of 10.5 g/m2 given in 84 hrs. Eight patients of 29 assessable for response achieved an objective response: 1 complete and 7 partial. The overall response rate was 28% (95% CI: 13-47%).
If we accept 4-day G4 leukopenia as a reliable cutoff for safety, ifosfamide intensification cannot be substantially exploited over already available schedules with the combination of ifosfamide and anthracyclines.
Tumori 85(4):229-33. · 0.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Reports on FAMTX (5-FU, high-dose methotrexate and doxorubicin), EAP (etoposide, doxorubicin, cisplatin) and PELF (cisplatin, epirubicin, leucovorin and 5-FU) showed that survival rates remain very poor (median 7.3 months for FAMTX, 6.1 for EAP and 8.1 for PELF), and toxic deaths and heavy toxicity are of concern in planning these therapies. Moreover, for the FAMTX regimen, the method of methotrexate administration requires hospitalization for all pts and the control of MTX plasma levels for the adjustment of the leucovorin dosage. EAP regimen is delivered in an 8-day period and is also very difficult to administer on an outpatient basis. The original PELF regimen with epirubicin on day 1 and 5 is hampered by 9% of severe hematological and gastrointestinal toxicity. In a time of increasing financial constraints, and due to the still lacking evidence of a significant impact of combination chemotherapy on survival, in November ‘92 we started a study with a regimen feasible on an outpatient basis. Only chemo-nalve pts with histologically proven advanced gastric cancer and measurable disease (CT scan, ultrasound) were enrolled. A PELF-like regimen carried out on an outpatient basis was conducted as follows: cisplatin 30 mg/m2 day 1, 2, 3; 5-FU 500 mg/m2 d 1, 2, 3 i.v. bolus; l-leucovorin 100 mg/m2 d 1,2, 3 i.v. bolus preceding 5-FU, and epiadriamycin 50 mg/m2 d 1 only; granisetron antiemetic 3 mg i.v. for 3 days. The cycle was repeated every 3 weeks, or to bone marrow recovery, without the use of hematological growth factors. To date, 35 pts have entered the study, and 29 are evaluable for response. Median age is 59 years (range 32–71). Median PS at entry was 60 (range 50-90). Median number of administered cycles was 5 (range 1–10), for a total of 167 cycles. Five complete responses and 12 partial remissions were achieved, for an overall response rate of 55% (95% CL ± 18%); 7stable disease and 5 progressions were also noted. The median duration of response was 7 months (range 3-22+), Taxicity was mainly hematological, with leucopenia grade 3 in 11 pts and grade 4 in 4 pts, thrombocytopenia grade 1 in 1pt, and grade 2 and 3 in 2 pts, respectively. In conclusion, this regimen seems feasible on an outpatient basis, allowing the reduction of the cost of the treatment. The response rate is sufficiently high to merit further study.
European Journal of Cancer. 32.
