A multicenter, randomized, double blind placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer.

Aim Of The Study: To evaluate the effectiveness of oral amoxicillin/clavulanate (25 mg/kg every 12 h) for prevention of fever and/or infection in neutropenic children with cancer.

Methods: Multicenter, prospective, randomized, double blind placebo-controlled trial.

Results: In the intention-to-treat analysis, amoxicillin/clavulanate had a 12% benefit increase in terms of reduction in the incidence of febrile or infectious episodes, compared with placebo [44 of 83 (53%) vs.

Major and minor salivary glands tumours.

Malignant salivary gland tumours are rare. The most common tumour site is the parotid. Aetiologic factors are not clear.

Cancer of the nasopharynx.

Nasopharyngeal cancer (NPC) is quite rare throughout Europe, accounting for an annual incidence rate below 1 per 100.000, whereas the highest risk area is South East Asia. A predominant occurrence in males is to be noted.

Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer.

Background: The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate (pCR) in patients with locally advanced breast cancer (LABC) treated with combined modality therapy.

Patients And Methods: Stage IIIA/IIIB patients received three courses of induction chemotherapy (ICT) with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by local therapy (total mastectomy or segmental mastectomy with axillary nodes dissection) and adjuvant chemotherapy (ACT) with three courses of CEF alternated with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Patients were randomized to receive ICT and ACT every 3 weeks (arm A, 'standard treatment') or every 2 weeks with granulocyte-macrophage colony-stimulating factor (GM-CSF) support (arm B, 'dose-dense treatment').

Prevalence of the E1317Q variant of the APC gene in Italian patients with colorectal adenomas.

Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas.

An estimate of prostate cancer prevalence in Italy.

Estimates of the total number of men with a previous diagnosis of prostate cancer in Italy range from 55,000 to 135,000. This wide range of variation is largely due to uncertainties on the number of protein-specific antigen-detected, asymptomatic cases. The number of clinically detected cases, including cases with advanced disease, is less subject to uncertainty, with reasonable estimates ranging from 45,000 to 60,000.

Risk associated with pregnancy in hypertrophic cardiomyopathy.

Objectives: We sought to assess mortality and morbidity in pregnant women with hypertrophic cardiomyopathy (HCM).

Background: The risk associated with pregnancy in women with HCM is an important and increasingly frequent clinical issue for which systematic data are not available and a large measure of uncertainty persists.

Methods: Maternal mortality in 91 consecutively evaluated families with HCM was compared with that reported in the general population.

Time to progression in metastatic breast cancer patients treated with epirubicin is not improved by the addition of either cisplatin or lonidamine: final results of a phase III study with a factorial design.

Purpose: To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer.

Patients And Methods: Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study.

[Bonferroni in biomedical research].

The statistical methods for multiple comparisons are described in the paper. The pros and cons of Bonferroni correction versus more recent methods such as Holm correction are outlined. The lack of scientific consensus on the methods to be used in the different areas of biomedical research is shown by the disagreements, often quite harsh, between different statisticians.

Randomized trial comparing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with rotational CMF, epirubicin and vincristine as primary chemotherapy in operable breast carcinoma.

Background: According to the overview of Early Breast Cancer Trialists' Collaborative Group, anthracycline containing regimens are superior to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy for breast carcinoma, but no comparative information is available in terms of primary chemotherapy. In the current randomized controlled trial, the authors compared CMF with a chemotherapy regimen including CMF, epirubicin, and vincristine (CMFEV).

Methods: Two hundred eleven patients with Stages I and II palpable breast carcinoma and tumor diameter > 2.

Objective response to treatment as a potential surrogate marker of survival in breast cancer.

Until recently, objective tumor response to chemotherapy was used as the primary endpoint in phase II trials aimed at assessing the anti-tumor activity of new drugs. However, it was not accepted as a surrogate endpoint of survival for efficacy trials in solid tumors, and it was not believed to be associated with survival benefit. The recent demonstration that objective response is indeed a valid surrogate endpoint of survival in colorectal cancer, together with strong indirect evidence supporting a similar role of response in breast cancer, opens new possibilities for both the design of trials in metastatic breast cancer and the clinical decision in individual patients with the disease.

Cancer of the oropharynx.

Oropharyngeal cancer is a rare tumour. Tobacco use and alcohol consumption are recognised as major risk factors. Several carcinogens, occupational exposures and vitamin deficiencies represent the most significant predisposing factors.

Bladder cancer.

Bladder cancer is the second most frequent tumour of the urogenital tract. Tobacco smoke has been shown to increase the risk of bladder cancer two- to fivefold as well as the exposure to metabolites of aniline dyes and other aromatic amines. Seventy-five per cent of bladder cancers are superficial at initial presentation, limited to the mucosa, submucosa, or lamina propria.

MRI metrics as surrogate markers for clinical relapse rate in relapsing-remitting MS patients.

Objective: To formally validate metrics derived from conventional MRI as surrogate endpoints for relapse rate in MS.

Background: Although metrics derived from MRI are used widely in clinical trials of MS, a formal statistical validation of MRI metrics as surrogate endpoints for clinical outcome in MS is lacking.

Methods: A validation procedure was applied to clinical and MRI data collected in the context of a randomized, double-blind, placebo-controlled trial of glatiramer acetate in patients with relapsing-remitting MS.

Modelling new enhancing MRI lesion counts in multiple sclerosis.

Magnetic resonance imaging (MRI) has been established as the most relevant paraclinical tool for diagnosing and monitoring multiple sclerosis (MS). In this context, counting the number of new enhancing lesions on monthly MRI scans is widely used as a surrogate marker of MS activity when evaluating the effect of treatments. In this study, we investigated whether parametric models based on mixed Poisson distributions (the Negative Binomial (NB) and the Poisson-Inverse Gaussian (P-IG) distributions) were able to provide adequate fitting of new enhancing lesion counts in MS.

Sample size estimations for MRI-monitored trials of MS comparing new vs standard treatments.

The authors estimated the sample sizes needed for exploratory trials of MS assessing the efficacy of new treatments in reducing the number of new enhancing lesions vs those of interferon-beta or glatiramer acetate. The sample sizes per arm ranged from 868 (effect: 20%) to 94 (effect: 50%) for patients with relapsing-remitting MS and from 2,484 (effect: 20%) to 361 (effect: 50%) for patients with secondary progressive MS. In MS, exploratory trials of new vs available therapies require large numbers of patients, even when MR end-points are used.

Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer.

The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery.

Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain.

The hypothesis was tested that amino acid substitutions in specific positions within human leukocyte antigen class I heavy chain would have different impacts on transplant-related mortality (TRM) in patients receiving transplanted bone marrow from unrelated donors. One hundred patients and their unrelated donors were typed by sequence-based typing for the human leukocyte antigen (HLA)-A, -B, and -C loci. All pairs were matched for DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 loci.

Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO).

One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P =.

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).

Background: The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial.

Methods: From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression.

High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: results of a randomized trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group.

Purpose: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma.

Patients And Methods: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT.

Clinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets.

Objective: A new parametric simulation procedure based on the negative binomial (NB) model was used to evaluate the sample sizes needed to achieve optimal statistical powers for parallel groups (with (PGB) and without (PG) a baseline correction scan). It was also used for baseline versus treatment (BVT) design clinical trials in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), when using the number of new enhancing lesions seen on monthly MRI of the brain as the measure of outcome.

Methods: MRI data obtained from 120 untreated patients with RRMS selected for the presence of MRI activity at baseline, 66 untreated and unselected patients with RRMS, and 81 untreated and unselected patients with SPMS were fitted using an NB distribution.

Diagnostic value of the acid-labile subunit in acromegaly: evaluation in comparison with insulin-like growth factor (IGF) I, and IGF-binding protein-1, -2, and -3.

In normal subjects the main form of circulating insulin-like growth factor (IGF) is the 150-kDa complex. This complex is formed by the IGF peptide, the acid-stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS). Experimental and clinical data have demonstrated that ALS is primarily under the control of GH and plays a critical role in maintaining constant levels of circulating IGF-I.

Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a randomized study. GISCAD, IOR and collaborating centers.

Background: We have recently suggested that bolus 5-fluorouracil (5-FU) may work via a RNA directed mechanism while continuous infusion 5-FU may kill cells via a thymidylate synthase related pathway. It may thus be possible to selectively modulate each schedule biochemically. We have compared an alternating regimen of bolus and continuous infusion 5-FU, selectively modulated for the schedule of administration, with modulated bolus 5-FU in advanced colorectal cancer patients.