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F Nuzzo, C Gallo,
S Lastoria,
M Di Maio,
M C Piccirillo,
A Gravina,
G Landi,
E Rossi,
C Pacilio,
V Labonia, [......],
M De Laurentiis,
M D'Aiuto,
M Di Bonito,
G Botti,
P Giordano,
G Daniele,
A Morabito,
N Normanno,
A de Matteis,
F Perrone
[show abstract]
[hide abstract]
ABSTRACT: To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid.
A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan.
Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively).
In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.
Annals of Oncology 03/2012; 23(8):2027-33. · 6.43 Impact Factor
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[show abstract]
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ABSTRACT: The relationship between periodontal disease and preterm labour has been target of several studies with contrasting findings. The aim of this study is to verify the association between periodontal diseases in pregnant women and threatened preterm labour (TPL).
Two hundred and twenty pregnant women were enrolled in a matched prospective case-control study. Matching factors were age, parity and date of admission. Cases were defined as women admitted with a diagnosis of TPL before the 37th week; controls were defined as women with term labour (= or > 37 weeks) in the same ward. Primary exposure was defined as the presence of at least one tooth with probing depth (PD) >6 mm and BOP+. Average pocket depth, full-mouth bleeding on probing (FMBS) and the presence of plaque (FMPS) were also investigated. Matched univariate (McNemar's test and Wilcoxon signed rank test) and multivariate (conditional logistic regression model) analyses were performed.
At least one PD >6 mm BOP+ was found in 30 TPL cases (27.3%) and 37 controls (33.6%), without significant difference (P=0.27). There was also no difference was found in shallow pockets. The average pocket depth was similar in TPL cases (2.67 mm) and controls (2.78 mm) (P=0.29). The average FMPS was 56.4% in the cases and 50.7% in the controls, while FMPS was 36.5% and 39.6%, respectively, though these differences are not statistically significant (P=0.26 and P=0.42, respectively).
From our study, there seems to be no association between threatened pre-term labour and periodontal disease.
Minerva stomatologica 10/2007; 56(9):415-26.
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S Pignata,
G Scambia,
C Pisano,
E Breda,
M Di Maio,
S Greggi,
G Ferrandina,
D Lorusso,
V Zagonel,
A Febbraro,
N Riva,
V De Rosa, C Gallo,
F Perrone
[show abstract]
[hide abstract]
ABSTRACT: Anthracyclines and platinum derivates are active drugs for advanced endometrial carcinoma (AEC), but new schedules with higher efficacy and better tolerability are needed. A phase II study was conducted to describe activity and tolerability of carboplatin (C)+pegylated liposomal doxorubicin (PLD) in patients with AEC. Patients with chemonaive AEC, PS < or = 2, aged < 75 years, with at least one measurable lesion were eligible. Treatment was C (area under curve 5)+PLD (40 mg m(-2)) on day 1 every 4 weeks, up to six cycles. Forty-two patients were needed in a single-stage design, with at least 13 objective responses to define the treatment active. Forty-two patients were enrolled. Median age was 64 years (31-74). A total of 64% of patients were recurrent while 36% were advanced. Three complete (7%) and 22 partial responses (52%) were observed, for an overall response rate of 59.5% (95% exact CI: 43.3-74.3). One death potentially related to treatment was recorded (death at home for unknown reasons after 6th cycle). Other relevant toxicities (% of patients) were grade 3/4 neutropaenia 33%/14%, febrile neutropaenia 5%, grade 3/4 thrombocytopaenia 17%/5%, grade 3/4 anaemia 31%/2%. Skin toxicity was mild: grade 1 14%, grade 2 10%, grade 3 5%. Hair loss: complete 5%, partial 12%. The combination of carboplatin and PLD shows good activity and favourable toxicity as first-line chemotherapy of patients with AEC, deserving further studies in this setting.
British Journal of Cancer 06/2007; 96(11):1639-43. · 5.04 Impact Factor
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C Pacilio,
A Morabito,
F Nuzzo,
A Gravina,
V Labonia,
G Landi,
E Rossi,
E De Maio,
M Di Maio,
G D'Aiuto,
G Botti,
N Normanno,
P Chiodini, C Gallo,
F Perrone,
A de Matteis
[show abstract]
[hide abstract]
ABSTRACT: The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m-2 (D) with the combination of docetaxel 80 mg m-2 and epirubicin 75 mg m-2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n=26) and D arms (n=25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy.
British Journal of Cancer 06/2006; 94(9):1233-6. · 5.04 Impact Factor
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Archivos De Medicina Veterinaria - ARCH MED VET. 01/2006; 38(3).
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S De Placido,
M Lopez,
C Carlomagno,
G Paoletti,
S Palazzo,
L Manzione,
C Iannace,
G P Ianniello,
F De Vita,
C Ficorella, [......],
G Pistillucci,
M Gemini,
E Cortesi,
V Adamo,
N Gebbia,
S Palmeri, C Gallo,
F Perrone,
G Persico,
A R Bianco
[show abstract]
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ABSTRACT: The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.
British Journal of Cancer 11/2005; 93(8):896-904. · 5.04 Impact Factor
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F Perrone,
M Marangolo,
F Di Costanzo,
G Colucci,
L Repetto,
M Merlano,
S De Placido,
V Torri,
G Comella,
R Labianca,
V Parisi, C Gallo
Annals of Oncology 12/2004; 15(11):1722-3. · 6.43 Impact Factor
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C Gridelli, C Gallo,
M Di Maio,
E Barletta,
A Illiano,
P Maione,
S Salvagni,
F V Piantedosi,
G Palazzolo,
O Caffo,
A Ceribelli,
A Falcone,
P Mazzanti,
L Brancaccio,
M A Capuano,
L Isa,
S Barbera,
F Perrone
[show abstract]
[hide abstract]
ABSTRACT: Docetaxel (75 mg m(-2) 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m(-2) for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, < or =75 years, ECOG PS < or =2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77-1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3-4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.
British Journal of Cancer 12/2004; 91(12):1996-2004. · 5.04 Impact Factor
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M Di Maio,
C Gridelli, C Gallo,
L Manzione,
L Brancaccio,
S Barbera,
S F Robbiati,
G P Ianniello,
F Ferraù,
E Piazza,
L Frontini,
F Rosetti,
F Carrozza,
A Bearz,
M Spatafora,
V Adamo,
L Isa,
R V Iaffaioli,
E Di Salvo,
F Perrone
[show abstract]
[hide abstract]
ABSTRACT: Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment.
British Journal of Cancer 06/2004; 90(12):2288-96. · 5.04 Impact Factor
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M Di Maio,
F Perrone, C Gallo,
R V Iaffaioli,
L Manzione,
F V Piantedosi,
S Cigolari,
A Illiano,
S Barbera,
S F Robbiati, [......],
Matteo Vasta,
Cesare Bumma,
Alfredo Celano,
Sergio Bretti,
Giuseppe Nettis,
Annamaria Anselmo,
Rodolfo Mattioli,
Cecilia Nisticò,
Annamaria Aschelter,
Paola Foa
[show abstract]
[hide abstract]
ABSTRACT: The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.
British Journal of Cancer 10/2003; 89(6):1013-21. · 5.04 Impact Factor
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M Di Maio,
F Perrone, C Gallo,
R V Iaffaioli,
L Manzione,
F V Piantedosi,
S Cigolari,
A Illiano,
S Barbera,
S F Robbiati,
E Piazza,
G P Ianniello,
L Frontini,
E Veltri,
F Castiglione,
F Rosetti,
E De Maio,
P Maione,
C Gridelli
[show abstract]
[hide abstract]
ABSTRACT: The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.Keywords: supportive care, lung cancer, polypharmacotherapy, concomitant drugs
British Journal of Cancer 09/2003; 89(6):1013-1021. · 5.04 Impact Factor
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F Perrone, C Gallo,
B Daniele,
G B Gaeta,
F Izzo,
G Capuano,
L E Adinolfi,
R Mazzanti,
F Farinati,
S Elba, [......],
A Aiello,
I De Sio,
F Castiglione,
M Russo,
M Persico,
M Felder,
O G Manghisi,
E De Maio,
M Di Maio,
S Pignata
[show abstract]
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ABSTRACT: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment.
The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death.
496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis.
the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.
Current Pharmaceutical Design 01/2002; 8(11):1013-9. · 3.87 Impact Factor
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R Parasole,
F Izzo,
F Perrone,
S Pignata,
M G Galati,
E Leonardi,
F Castiglione,
R Orlando,
G Castello,
G Esposito, C Gallo,
B Daniele
[show abstract]
[hide abstract]
ABSTRACT: Prognosis of patients with hepatocellular carcinoma (HCC) is assessed by using indexes based on clinical and instrumental parameters. The Cancer of the Liver Italian Program (CLIP) staging system combines the Child-Pugh classification with tumor size, portal invasion, and alpha-fetoprotein and predicts the outcome of HCC patients more precisely than the Okuda staging system. Serum levels of a number of biological variables have been found to be increased in patients with HCC and are associated with different outcomes. Our aims in this study were to test the prognostic role of the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), interleukin 6 (IL-6), and anti-p53 and to assess whether the addition of any of the above serum markers could further improve the predictive ability of the CLIP score.
Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 were assayed in 80 patients with HCC and correlated with their outcomes. Nonparametric procedures were applied to test correlations between serum sICAM-1, sIL-2R, IL-6, anti-p53, and other prognostic factors. For survival analyses, the product-limit method, log-rank test, and Cox proportional hazards model were applied.
Only serum levels of sIL-2R correlated with survival, which was longer for patients with lower values (< or =950 units/ml). However, with multivariate analysis sIL-2R did not confirm its predictive role when tested with the CLIP score as a covariate, with a hazard of death of 1.51 (95% confidence interval, 0.76-3.01).
Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 are not useful as prognostic factors for HCC in clinical practice. They do not improve the predictive ability of the CLIP score.
Clinical Cancer Research 12/2001; 7(11):3504-9. · 7.74 Impact Factor
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C Gridelli,
L Manzione,
F Perrone,
E Veltri,
R Cioffi,
M G Caprio,
L Frontini,
A Rossi,
E Barletta,
M L Barzelloni,
D Bilancia, C Gallo
[show abstract]
[hide abstract]
ABSTRACT: A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m(2)3-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial was the objective response rate. 31 objective responses among 50 patients were considered necessary to proceed to a phase 3 trial. 48 patients were enrolled (median age 59 years). Treatment was very well tolerated. 3 patients (6.2%) had a complete response and 23 (47.9%) a partial response, for an overall response rate of 54.2% (95% CI: 39.2-68.6). Median time to progression was 5.7 months (95% CI: 5.2-6.2). Median survival was 9.6 months (95% CI: 7.2-14.6), with a median follow-up time of alive patients of 12 months. At 1 year, the probability of being progression-free or alive was 0.16 and 0.43, respectively. In conclusion, carboplatin plus paclitaxel as given in the present study is very well tolerated but not sufficiently active to warrant phase 3 comparison with standard chemotherapy regimens.
British Journal of Cancer 02/2001; 84(1):38-41. · 5.04 Impact Factor
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[hide abstract]
ABSTRACT: Increasing age is a major risk factor for developing cancer and the number of older people is rapidly expanding. Therefore, cancer in the geriatric population is becoming an emerging problem. Older patients are extremely heterogeneous. Instruments collecting information related to comorbidity and disability, (which have both been demonstrated to affect the survival of elderly patients) may help treatment decision. The G.I.O.Ger (Gruppo Italiano di Oncologia Geriatrica) has validated a Comprehensive Geriatric Assessment (CGA) scale for geriatric cancer patients, and we recommend its use in clinical practice. Our findings suggest that cancer adversely affects physical performance and psychological status less than other comorbidities. Many aspects of physical limitations are not totally recognised by performance status, in particular those aspects of daily life that require instrumental activities and that may affect adherence to diagnostic or therapeutic protocols. Quality of life as a main objective in the management of elderly cancer patients is now recognized by many clinicians. In clinical practice. quality of life means maintenance of function and symptom control, and quality-of-life instruments rated by the patient rather than by clinicians should be preferred. Whether it is preferable to use cancer-specific or generic instruments is an ongoing debate.
Annals of Oncology 02/2001; 12 Suppl 3:S49-52. · 6.43 Impact Factor
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[show abstract]
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ABSTRACT: 5-Fluorouracil (FU) in association with folinic acid (FA) is the most frequently used chemotherapeutic agent in colorectal cancer but it often causes diarrhoea. Animal and human studies suggest that glutamine stimulates intestinal mucosal growth.
To determine if oral glutamine prevents changes in intestinal absorption (IA) and permeability (IP) induced by FU/FA.
Seventy chemotherapy naive patients with colorectal cancer were randomly assigned to oral glutamine (18 g/day) or placebo before the first cycle of FU (450 mg/m(2)) and FA (100 mg/m(2)) administered intravenously for five days. Treatment was continued for 15 days, starting five days before the beginning of chemotherapy. IA (D-xylose urinary excretion) and IP (cellobiose-mannitol test) were assessed at baseline and four and five days after the end of the first cycle of chemotherapy, respectively. Patients kept a daily record of diarrhoea, scored using the classification system of the National Cancer Institute (Bethesda, Maryland, USA). Duration of diarrhoea was recorded and the area under the curve (AUC) was calculated for each patient.
Baseline patient characteristics and basal values of IP and IA tests were similar in the two arms. After one cycle of chemotherapy, the reduction in IA (D-xylose absorption) was more marked in the placebo arm (7.1% v 3. 8%; p=0.02); reduction of IP to mannitol was higher in the placebo arm (9.2% v 4.5%; p=0.02); and urinary recovery of cellobiose was not different between the study arms (p=0.60). Accordingly, the cellobiose-mannitol ratio increased more in the placebo arm (0.037 v 0.012; p=0.04). Average AUC of diarrhoea (1.9 v 4.5; p=0.09) and average number of loperamide tablets taken (0.4 v 2.6; p=0.002) were reduced in the glutamine arm.
Glutamine reduces changes in IA and IP induced by FU and may have a protective effect on FU induced diarrhoea.
Gut 02/2001; 48(1):28-33. · 10.11 Impact Factor
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C Gridelli,
L Frontini,
F Perrone, C Gallo,
M Gulisano,
S Cigolari,
F Castiglione,
S F Robbiati,
G Gasparini,
G P Ianniello,
A Farris,
M C Locatelli,
R Felletti,
E Piazza
[show abstract]
[hide abstract]
ABSTRACT: Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.
British Journal of Cancer 09/2000; 83(6):707-14. · 5.04 Impact Factor
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[show abstract]
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ABSTRACT: Proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the treatment of ulcerative colitis. Functional results may differ with different pouch designs. This randomized study aimed to evaluate the relative effectiveness of two-limb J and four-limb W reservoir designs in the so-called maturation period after ileostomy closure.
Twenty-four patients underwent ileal pouch-anal anastomosis for ulcerative colitis. Eleven were randomly assigned to the J-pouch group and 13 to the W-pouch group. Frequency of defecation and other functional data were collected at 4, 8, and 12 months after ileostomy closure. Maximum tolerated volume was assessed in the same period by a latex balloon inflated with water. Maximum resting anal pressure, maximum voluntary contraction, and the rectoanal inhibitory reflex were assessed in the preoperative period and at 4, 8, and 12 months after ileostomy closure.
Frequency of defecation decreased from 4 to 12 months after ileostomy closure in both groups (P = 0.04), but patients with a W-pouch had significantly lower values than patients with J-pouches (P < 0.01). Night-time defecation (P = 0.04) and use of antidiarrheals (P = 0.04) were significantly lower for patients with a W-pouch. Maximum tolerated volume was greater in the W-pouch group throughout the whole period (P = 0.01). Maximum resting anal pressure, maximum voluntary contraction, and rectoanal inhibitory reflex did not differ between the study arms.
Patients with W-pouch have better functional results than those with J-pouches in the "maturation period" after ileostomy closure.
Diseases of the Colon & Rectum 05/2000; 43(5):615-20. · 3.13 Impact Factor
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S De Placido,
R Lauria,
C Carlomagno,
F Perrone,
M De Laurentiis, C Gallo,
A Martignetti,
T Bellelli,
G Limite,
G Petrella,
A R Bianco
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ABSTRACT: To increase the dose-intensity of two drugs in metastatic breast cancer, we tested the feasibility, in phase I studies, of two schedules of epirubicin (E) and cyclophosphamide (C) - sequential (E--> C) and alternating (E/C) - with respect to the standard combination (EC). Drugs were given at three planned-dose levels, plus either G-CSF or GM-CSF. Patients with metastatic (30), inoperable stage IIIb (2) or inflammatory (7) breast cancer were treated. The doses of EC, given every 21 days (4 cycles), were 75/1500, 82.5/2250, 90/3000 mg/m2. In the E/C schedule, epirubicin was given at cycles 1, 3 and 5, and cyclophosphamide at cycles 2, 4 and 6. In the E--> C schedule, three cycles of epirubicin then three cycles of cyclophosphamide were administered. In both experimental schedules, drugs were given every 14 days for 6 cycles at doses of 100, 110, 120 mg/m2 (E) and 2000, 3000, 4000 mg/m2 (C). The average relative dose-intensity was 1.2-fold and 2-fold greater with E/C and E--> C, respectively, than with EC. The third level dose was feasible with all schedules. Grade 4 leucopenia occurred in 77% of patients. Thrombocytopenia was absent in 6 cases and grade 4 in 12 (30.8%). Eighty-one percent of patients on experimental schedules required red blood cell support versus 44.4% of patients on EC. At the third level, platelet transfusions were more frequent among patients treated with EC (27. 8%). Non-haematological toxicity was mild: about 20% of patients experienced grade 3 vomiting, irrespective of schedule. Only 2 patients had grade 3 mucositis; no patient developed heart failure. Fever (61% of patients) and bone pain (55.5% of patients) were relevant in the GM-CSF treated groups and 12 patients shifted to G-CSF. The overall response rate was 84.6%: 5/39 (12.8%) complete response and 28/39 (71.8%) partial response. At 30/9/98, median survival was 29.5 months, with no difference between patients with metastatic and stage IIIb/inflammatory breast cancer. Median follow-up of surviving patients was 62 months (range 17-83). The 5-year estimated survival was 19% (95% confidence intervals = 7-31%). Rapidly alternating or sequential cycles of epirubicin and cyclophosphamide with CSF support is a feasible strategy that allows a higher increase of dose-intensity of the single drugs. Hospitalization and anemia were more frequent with the experimental schedules, and thrombocytopenia with the standard schedule. Overall, this intensified therapy was very active.
International Journal of Oncology 08/1999; 15(2):339-46. · 2.40 Impact Factor
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S Pignata,
G Silvestro,
E Ferrari,
L Selvaggi,
F Perrone,
A Maffeo,
P Frezza,
G Di Vagno,
G Casella,
P Ricchi,
G Cormio, C Gallo,
F Iodice,
F Romeo,
R Fiorentino,
G Fortuna,
S Tramontana
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ABSTRACT: To evaluate the activity and toxicity of the combination of cisplatin (80 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8) in patients with carcinoma of the uterine cervix that has not been previously treated with chemotherapy.
Fifty patients with cervical cancer were enrolled onto this study (27 stage IB-III, 23 stage IVB-recurrent). A two-stage optimal Simon design was applied. Thirteen responders of 29 treated patients were required to proceed beyond the first stage, and 28 responders were needed overall.
Hematologic toxicity was mild, with neutropenia being the most frequent side effect. Nonhematologic toxicity was frequent but never severe; one patient had grade 3 peripheral neurotoxicity. Objective responses were recorded for 32 patients (64%): 11 patients (22%) achieved a complete response (CR) and 21 patients (42%) achieved a partial response (PR). The response rate was 81.5% in patients with IB-III stage (25.9% CR rate) and 43.5% in patients with IVB-recurrent disease (17.4% CR rate). Responses were seen both in stage IVB patients (one CR and two PRs, for an overall rate of 37.5%) and in patients with recurrent disease (three CRs + four PRs, for an overall rate of 46.7%).
The combination of cisplatin and vinorelbine is an active regimen in the treatment of patients with early-stage and advanced carcinoma of the uterine cervix. The hematologic and nonhematologic toxicity of this combination is mild.
Journal of Clinical Oncology 04/1999; 17(3):756-60. · 18.37 Impact Factor
