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A Farris

Publications and source records attributed to A Farris.

At least 19 recordsLinked to original sources
PubMed2005

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study.

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.

Adult↗
PubMed2005

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study.

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.

Adult↗
PubMed2005

Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients: a Southern Italy Cooperative Oncology Group phase II study.

Oxaliplatin 100 mg/m(2) iv on day 1, and capecitabine 1,000 mg/m(2) orally bid from day 1 (evening) to day 11 (morning) were administered every 2 weeks (OXXEL regimen) to 38 patients as first-line treatment for metastatic colorectal carcinoma. A total of 318 cycles were administered, with a median of 8 (range, 4-12) cycles per patient. Response rate (RR) was 45% (95% confidence interval (CI), 29%-62%), with 7 complete responses and 10 partial responses; furthermore, 12 patients showed a stable disease, so that a disease control was achieved in 29 (76%) patients. RR was greater among patients with performance status 0 (52%), without weight loss (52%), younger than 65 years (50%), and previously unexposed to adjuvant chemotherapy (48%), while no correlation was found with the actually delivered oxaliplatin dose intensity. Overall, haematological side effects were negligible, with no case of grade 4 toxicity, and only one patient suffering from an episode of grade 3 neutropenic fever. Severe anaemia occurred in 4 (11%) patients, and grade 3 neuropathy affected 9 (24%) patients. Median progression-free survival was 7.9 (95% CI, 6.2-9.6) months, and median overall survival has not been reached yet. In conclusion, the OXXEL regimen resulted safe and active, and it deserves further evaluation in metastatic colorectal cancer patients.

Adult↗
PubMed2005

Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial.

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.

Adult↗
PubMed2005

Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines.

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m(-2) on days 1 and 15, PTX 60 mg m(-2) on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m(-2) every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization (WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable.

Adult↗
PubMed2005

A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer.

The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.

Adult↗
PubMed2005

Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer.

This study compares two cytotoxic regimens comprising the same dose and schedule of cisplatin (CP) plus vinorelbine (VNR) or gemcitabine (GEM) administered under the same schedule to patients with advanced non-small cell lung cancers (NSCLC). From April 1998 to February 2003, 285 patients were randomised to receive either VNR 25 mg/m(2) on days 1 and 8 as an intravenous (i.v.) bolus plus CP 75 mg/m(2) on day 1 (regimen A) or GEM 1200 mg/m(2) on days 1 and 8 as an i.v. 30-min infusion plus CP 75 mg/m(2) on day 1 (regimen B). Both treatments were recycled every 21 days. If no progression had occurred after six cycles, the patients continued to receive VNR or GEM monochemotherapy weekly. Cross-over of the two single agents was considered if disease progression occurred. Objective response (OR), time to progression (TTP) and overall survival (OS) were analysed according to the intention-to-treat principle. 272 patients were ultimately eligible (137 on A and 135 on B). Their main characteristics were: male/female ratio 214/58; median age 63 (range 32-77) years; median Karnofsky Performance Status (PS) 80 (range 70-100); stage IIIB 34%, stage IV 61%, recurrent disease 5%; histology - epidermoid 29%, adenocarcinoma 53%, other NSCLC 18%. The characteristics of the patients in the two arms were well matched. The following response rates were observed in regimens A and B, respectively: complete response (CR) 0.7% and 3.7%, partial response (PR) 31.9% and 22.2% (P = 0.321). Median CR+PR duration was 8 months in both arms. Clinical benefit represented by an improvement in symptoms was evident in 25.7% and 28.1%, respectively. Median TTP was 5 months in both arms and median OS 11 months in both arms. Grade III-IV neutropenia occurred in 30.7% and 17.7% of the patients in arms A and B, respectively (P = 0.017); thrombocytopenia occurred in 0% and 9.3% (P = 0.004), respectively. No difference in the incidence of anaemia was observed. Non-haematological toxicity was generally mild: a higher incidence of grade 1-2 peripheral neurotoxicity and grade 1-2 local toxicity with regimen A and grade 1-2 liver toxicity with regimen B was reported. A pharmaco-economic comparison showed a difference between the two doublets, principally due to the different costs of VNR and GEM. Under the study conditions the combination of VNR or GEM with the same dose and schedule of CP produced similar OR, clinical benefits, TTP and OS in advanced NSCLC, and only mild toxicological differences were observed. Pharmaco-economic evaluation favoured the CP + VNR doublet.

Adult↗
PubMed2003

Irinotecan plus leucovorin-modulated 5-fluorouracil I.V. bolus every other week may be a suitable therapeutic option also for elderly patients with metastatic colorectal carcinoma.

The aim of this study was to assess the safety and efficacy of biweekly irinotecan plus leucovorin-modulated 5-fluorouracil i.v. bolus in metastatic colorectal carcinoma according to the age of patients. For this purpose, we have analysed 108 patients randomly allocated to receive irinotecan 200 mg m(-2) i.v. (1-h infusion) on day 1, and L-leucovorin 250 mg m(-2) i.v. (1-h infusion) plus 5-fluorouracil 850 mg m(-2) i.v. bolus on day 2 every 2 weeks (IRIFAFU) in our previous SICOG 9801 trial. According to age, patients were retrospectively divided into three groups: younger (</=54 years, n=37), middle-aged (55-69 years, n=64), and elderly (>/=70 years, n=17). Apart from gender, pretreatment characteristics were well balanced across the three groups. WHO grade >/=3 neutropenia and diarrhoea affected on the whole 46 and 16 patients, respectively, without any significant difference according to age-grouping. Patients aged </=54 years stayed on therapy for a longer time (median 24 vs 14-15 weeks), and received more cycles (median 9 vs 7), than the older ones. Only one patient in the young group withdrew consent to therapy as opposed to four patients each in the aged and elderly one. Response rate was 38% for younger patients, 34% for aged, and 35% for the elderly ones. Median time to progression was 7.4, 8.0, and 5.3 months, and median survival time was 13.4, 15.3, and 13.9 months, respectively. We conclude that IRIFAFU given every other week may represent a suitable therapeutic option also for elderly patients with metastatic colorectal carcinoma.

Adenocarcinoma↗
PubMed2003

Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial.

BACKGROUND: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen. PATIENTS AND METHODS: Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease. RESULTS: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation. CONCLUSIONS: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.

Age Factors↗
PubMed2003

The usefulness of 99mTc tetrofosmin scintigraphy in patients with breast cancer recurrences.

To verify the usefulness of 99mTc tetrofosmin scintigraphy in the follow-up of breast cancer patients, we studied 72 surgically treated breast cancer patients with suspected local recurrences (20 cases) or distant metastases (52 cases) at clinical examination and/or at conventional imaging procedures (CIPs). In all patients, a whole-body scan followed by planar and single photon emission tomography (SPET) images of selected sites were acquired 10 min after the intravenous injection of 740 MBq of 99mTc tetrofosmin, using a rectangular dual-head gamma camera equipped with high-resolution parallel-hole collimators. Loco-regional recurrences were diagnosed in 19 patients and distant metastases in 44 cases, while benign lesions were ascertained in nine cases. 99mTc tetrofosmin SPET showed higher sensitivity, specificity and accuracy per patient than did CIP (96.8% vs 85%, 77.7% vs 55.5% and 94.4% vs 81.1%, respectively) with statistical significance for accuracy (P <0.05). The combined use of SPET and CIP achieved 100% sensitivity and 98.6% accuracy. Planar imaging did not give additional information in respect of either SPET or CIP, showing significantly lower sensitivity and accuracy values (47.6% and 52.8%, respectively). Our data seem to suggest that 99mTc tetrofosmin SPET, but not planar, may be useful in the follow-up for the detection of loco-regional and distant recurrences in patients with breast cancer. The technique can play a complementary role to conventional diagnostic imaging procedures in selected patients.

Adult↗
PubMed2003

Randomized, controlled, multicenter phase III trial of standard-dose fluorouracil-epirubicin-cyclophosphamide (FEC), compared with time-intensive FEC (FEC-G) and mitoxantrone-methotrexate-mitomycin C (MMM-G) in metastatic breast carcinoma.

The purpose of this multicenter phase III trial was to assess the impact of a time-intensification of FEC (fluorouracil, epirubicin, cyclophosphamide) and MMM (mitoxantrone, methotrexate, mitomycin C) regimens, supported by lenograstim (G-CSF) on the objective response rate, time to progression and survival of patients with chemotherapy-naive metastatic breast cancer (mbc). Women with mbc were randomized to receive as first-line chemotherapy either standard-dose FEC (all doses in mg/m2): arm A (500, 75, 500 every 21 days), or time-intensified FEC-G: arm B (500, 75, 500 every 14 days), or time-intensified MMM-G: arm C (mitoxantrone 10, methotrexate 35 every 14 days and mitomycin C 10 every 28 days), both with support of lenograstim (G-CSF 150 microg/m2/day s.c. for 10 days). All study treatments were administered for six cycles. Eligible female patients were in the 31-70 year range with histologically proven mbc, and measurable or evaluable disease. An intent-to-treat analysis was performed. The overall response rate (CR + PR, intent-to-treat analysis) was significantly improved in the time-intensified FEC-G regimen (69%) in comparison with standard-dose FEC (41%), p=0.002. Time-intensified MMM-G (51%) did not lead to a significant improvement in the response rate. The percentage of complete responses was significantly higher in the FEC-G arm as compared to standard-dose FEC (17% vs. 4.7%; p=0.002). The median duration was longer in the intensified-dose arms without, however, achieving a statistically significant improvement. The median time to progression (TTP), and the median survival time did not differ between the three treatment arms. Grade 3-4 leukopenia was significantly higher (p<0.001) in the standard FEC regimen-treated patients. Thrombocytopenia was significantly higher (p<0.001) in both intensified regimens. Alopecia and mucositis were significantly more frequent in both anthracycline-containing regimens (p=0.003). Other hematological and non hematological toxicities were similar in the 3 treatment arms. The increase of dose-intensity of both FEC and MMM regimens improved activity, but not efficacy as compared to standard FEC regimen in our group of chemotherapy-naive, metastatic breast cancer patients.

Adult↗
PubMed2002

Restricted specificity of intermolecular spreading to endogenous La (SS-B) and 60 kDa Ro (SS-A) in experimental autoimmunity.

Intermolecular spreading of humoral autoimmunity to different components of the Ro (SS-A) and La (SS-B) ribonucleoprotein (RNP) complex has been reported following immunization with a single component of the complex. Although the immune response to the immunizing antigen is polyclonal and diversified, little is known about the specificity of the recruited autoimmune responses to the endogenous Ro and La antigens which drive B-cell spreading. To determine the specificity of intermolecular spreading to La, we examined sera from 52 kDa Ro (Ro52)- and 60 kDa Ro (Ro60)-immunized C3H/HeJ mice for reactivity with recombinant fragments spanning endogenous mouse (m)La by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Sera from mice primed and boosted with recombinant Ro52 and Ro60 showed reactivity restricted to the COOH-terminal fragment of mLa (aa361-415). The recruited anti-La response was species-specific, cross-reacting weakly with the corresponding region on the human La molecule, and was abrogated by the preabsorption of the Ro-immune sera with mLa 361-415. Analogous experiments using recombinant mRo60 fragments spanning the mRo60 molecule revealed a similar pattern of oligoclonality in the specificity of anti-Ro60 autoimmunity following active immunization with La and Ro52. These results suggest that intermolecular-intrastructural T-B help is limiting in this model, and reveal unsuspected immunodominance of selected Ro-La epitopes in the spreading of the autoantibody response to these structures. The focusing of the recruited autoantibody response to these COOH-terminal regions of the Ro and La polypeptides may also reflect the surface accessibility of these regions in La-Ro RNP.

Animals↗
PubMed2002

Addition of either irinotecan or methotrexate to bolus 5-fluorouracil and high-dose folinic acid every 2 weeks in advanced colorectal carcinoma: a randomised study by the Southern Italy Cooperative Oncology Group.

PURPOSE: The purpose of this study was to compare the activity and toxicity of the combination of irinotecan (IRI) plus folinic acid (FA)-modulated 5-fluorouracil (5-FU) i.v. bolus with a regimen of double modulation of 5-FU with methotrexate (MTX) and FA in patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Two-hundred and thirty-four patients were enrolled: 118 patients received IRI 200 mg/m2 (90-min i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and 5-FU 850 mg/m2 (i.v. bolus) on day 2 (IRIFAFU), and 116 patients received MTX 750 mg/m2 (2-h i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and FU 800 mg/m2 (i.v. bolus) on day 2 (MTXFAFU). Both cycles were repeated every 2 weeks until progression or to a maximum of 16 cycles. Response rate (RR) was the main end point of the study; responses were assessed every four cycles and confirmed after 2 additional months of treatment. RESULTS: RR was significantly greater with IRIFAFU (36%) than with MTXFAFU (20%) (P <0.001). Multivariate analysis showed that IRIFAFU was significantly associated with a greater activity (P = 0.028). Median progression-free survival was longer with IRIFAFU than with MTXFAFU (7.2 months compared with 4.8 months; P = 0.048). Median survival time (MST) did not differ between the two arms (14.7 months compared with 14.8 months, respectively). Patients not receiving second-line chemotherapy, however, lived longer when treated in the first-line with IRIFAFU (MST 11.9 months compared with 6.4 months; P = 0.038). IRIFAFU caused a significantly greater occurrence of grade 3 or 4 neutropenia (40% compared with 9%; P = 0.001) and diarrhoea (13% compared with 4%; P = 0.024), but a significantly lower incidence of stomatitis (3% compared with 12%; P = 0.007), than the comparative regimen. CONCLUSIONS: IRIFAFU appeared comparable in terms of activity and toxicity with other weekly or biweekly bolus or infusional combination regimens. IRIFAFU, however, seems easier to administer, because it does not require infusional catheter or pump devices, and it is less expensive. It may represent a new option for treating advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed2002

BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling.

BACKGROUND: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). PATIENTS AND METHODS: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. RESULTS: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P <0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. CONCLUSIONS: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.

Adult↗
PubMed2002

[Prevention of periodontopathy and oral mucositis during antineoplastic chemotherapy. Clinical study].

BACKGROUND: Oral mucositis is a common side effect of chemotherapy, with a multifactorial etiology: the direct toxicity of cancer therapy on the normal cells, reduced immunitary defences, presence of bacteria in the oral cavity. The aim of this study is to assess the clinical effectiveness of a preventive protocol of oral mucositis and periodontopathy during antineoplastic chemotherapy. METHODS: The design of the study was a longitudinal evaluation of 30 patients undergoing antineoplastic chemotherapy at the out-patients Department of Oncology of the University of Sassari. The study lasted one year and was carried out at the Dentistry Department of the University of Sassari. The patients were motivated to home oral hygiene, underwent professional oral hygiene and clorexidine rinses were prescribed. Visible plaque index (VPI) and gingival bleeding index (GBI) were taken from each patient as periodontal indices, and the state of the mucosa was evaluated according to the WHO recommendations (1975). The control group was composed by 33 patients. RESULTS: The values of the bleeding and plaque indices were considerably diminished between the first and the last visit, in nearly all the patients; the incidence of oral mucositis in the treated group was 20%, while in the control group it was 66%. 5-fluoruracil was always involved. CONCLUSIONS: According to the results observed, the conclusion is drawn that the professional and home oral hygiene and the use of clorexidine, can reduce the incidence of oral mucositis as a side effect of antineoplastic chemotherapy.

Adult↗
PubMed2001

Sequential tamoxifen and aminoglutethimide versus tamoxifen alone in the adjuvant treatment of postmenopausal breast cancer patients: results of an Italian cooperative study.

PURPOSE: To determine whether switching patients from tamoxifen to antiaromatase treatment would prevent some of the relapses or deaths that we assume would occur if tamoxifen were continued. PATIENTS AND METHODS: Three hundred eighty postmenopausal breast cancer patients receiving adjuvant tamoxifen treatment for 3 years were randomized to either continue tamoxifen for 2 more years or to switch to low-dose aminoglutethimide (250 mg daily) for 2 years. RESULTS: At a median follow-up of 61 months (range, 5 to 94 months), 59 events occurred in the tamoxifen group, and 55 occurred in the aminoglutethimide group. More treatment failures at distant sites, such as viscera (P =.02), were observed in the tamoxifen group. Although no differences in disease-free survival between the two groups have emerged so far, a significant trend favors aminoglutethimide in overall survival (P =.005) and breast cancer-specific survival (P =.06). Even if more patients in the antiaromatase group complained of drug-related side effects and more of them discontinued treatment (P =.0001), the number of cardiovascular events and, in general, of life-threatening adverse events was higher in the tamoxifen arm. CONCLUSION: Switching patients from tamoxifen to aminoglutethimide treatment resulted in comparable event-free survival, but longer overall survival was achieved in patients who were switched to aminoglutethimide as compared with those who continued to receive tamoxifen. Should these preliminary results be confirmed by larger studies with a similar design, which are now testing the effectiveness of the new, more active, and tolerable aromatase inhibitors, sequencing tamoxifen with an aromatase inhibitor could become a preferable alternative to tamoxifen alone in early breast cancer patients.

Aged↗
PubMed2000

Biweekly irinotecan or raltitrexed plus 6S-leucovorin and bolus 5-fluorouracil in advanced colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase II-III randomized trial.

PURPOSE: The aim of this randomised trial was to evaluate the activity and toxicity of a biweekly regimen including 6S-leucovorin-modulated 5-fluorouracil (LFA-5-FU), combined with either irinotecan (CPT-11 + LFA 5-FU) or raltitrexed (Tomudex) (TOM + LFA-5-FU), in advanced colorectal cancer patients, and to make a preliminary comparison of both these experimental regimens with a biweekly administration of LFA-5-FU modulated by methotrexate (MTX + LFA-5-FU). PATIENTS AND METHODS: One hundred fifty-nine patients with advanced colorectal carcinoma previously untreated for the metastatic disease (34 of them previously exposed to adjuvant 5-FU) were randomly allocated to receive: CPT-11, 200 mg/m2 i.v. on day 1, followed on day 2 by LFA, 250 mg/m2 i.v. infusion and 5-FU, 850 mg/m2 s i.v. bolus (arm A); TOM, 3 mg/m2 i.v. on day 1, followed on day 2 by LFA, 250 mg/m2 i.v. infusion and 5-FU, 1050 mg/m2 i.v. bolus (arm B); or MTX, 750 mg/m2 i.v. on day 1, followed on day 2 by LFA, 250 mg/m2 i.v. infusion and 5-FU, 800 mg/m2 i.v. bolus (arm C). Courses were repeated every two weeks in all arms of the trial. Response rate (RR) was evaluated after every four courses. The sample size was defined to have an 80% power to detect a 35% RR for each experimental treatment, and to show a difference of at least 4% in RR with the standard treatment if the true difference is 15% or more. RESULTS: The RRs were: 34% (95% confidence interval (95%, CI): 21%-48%) in arm A, including 3 complete responses (CRs) and 15 partial responses (PRs), 24% (95% CI: 14%-38%) in arm B, including 2 CRs and 11 PRs, and 24% (95% CI: 14%-38%), with 2 CRs and 11 PRs, in arm C. After a median follow-up time of 62 (range 18-108) weeks, the median time to progression was 38, 25, and 27 weeks for arm A, B, and C, respectively. With 94 patients still alive, the one-year probability of survival was 61%, 54%, and 59%, respectively. WHO grade 3 or 4 neutropenia and diarrhoea affected 46% and 16%, respectively, of patients treated with CPT-11 + LFA 5-FU. Median relative dose intensity over eight cycles (DI8) was 78% for CPT-11 and 82% for 5-FU. Severe toxicities of TOM + LFA-5-FU were neutropenia (16%) and diarrhoea (16%), but median relative DI8 was 93% for TOM, and 82% for 5-FU. CONCLUSIONS: CPT-11 + LFA-5-FU compares favorably in term of activity and toxicity with other combination regimens including CPT-11 and continuous infusional 5-FU. The hypothesis of a RR 15% higher than the MTX + LFA-5-FU treatment can not be ruled out after this interim analysis. The TOM + LFA 5-FU regimen showed a RR and a toxicity profile very close to the MTX + LFA 5-FU combination, and dose not deserve further evaluation in advanced colorectal cancer patients.

Adult↗