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Biomedical subjects

G Rosti

Publications and source records attributed to G Rosti.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.

BACKGROUND: The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. PATIENTS AND METHODS: Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. RESULTS: In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. CONCLUSION: Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).

Adult↗
PubMed2006

Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study.

HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with high-dose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2+ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P = 0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age > or = 50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2+ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age > or = 50 years or receiving multiple course of HDC should be considered at risk for CD.

Adult↗
PubMed2006

High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults.

Since the early 1980s high dose chemotherapy with autologous hematopoietic stem cell support was adopted by many oncologists as a potentially curative option for solid tumors, supported by a strong rationale from laboratory studies and apparently convincing results of early phase II studies. As a result, the number and size of randomized trials comparing this approach with conventional chemotherapy initiated (and often abandoned before completion) to prove or disprove its value was largely insufficient. In fact, with the possible exception of breast carcinoma, the benefit of a greater escalation of dose of chemotherapy with stem cell support in solid tumors is still unsettled and many oncologists believe that this approach should cease. In this article, we critically review and comment on the data from studies of high dose chemotherapy so far reported in adult patients with small cell lung cancer, ovarian cancer, germ cell tumors and sarcomas.

Adult↗
PubMed2006

Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients.

Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for BCR-ABL transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 12, 20 and at the end of study treatment (52 weeks) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of BCR-ABL transcript was expressed as the ratio of BCR-ABL to beta2-microglobulin (beta2M). We show that, following initiation of imatinib, the early BCR-ABL level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome and response. We propose this method as the method of choice for monitoring patients on imatinib therapy. QRT-PCR studies may be able to identify degrees of molecular response that predict both complete cytogenetic response and long term stability, as well as patterns of response that provide an early indication of relapse and imatinib resistance.

Antineoplastic Agents↗
PubMed2006

A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization.

We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 microg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34+ cells obtained after mobilization was 8.4 x 10(6)/kg in the filgrastim arm versus 5.8 x 10(6)/kg in the lenograstim arm versus 4.0 x 10(6)/kg in the molgramostim arm (P=0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (P<0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (P<0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34+ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.

Adjuvants, Immunologic↗
PubMed2006

Small cell lung cancer.

Small cell lung cancer accounts for 13-15% of all lung cancer worldwide. There has been a decrease in the number of cases, with no clear explanation, except probably to changing in smoking habits in the last two decades. In the early eighties, it became clear that SCLC was an extremely sensitive tumor as to radiation as to chemotheraputic agents. With cisplatinum etoposide combinations or cyclophosphamide, anthracycline and vincristine/etyoposide regimens responses were observed in 50-70%, with 20-30% complete remissions in extensive disease. For limited stage patients chemotherapy associated with thoracic radiation was able to produce a cure rate of 10-20%. The addition of prophylactic brain irradiation to limited stage cases has reduced mortality by a factor of nearly 5%. But despite these early good results no breakthrough came later on, and in the last decade or so, we are still facing this plateau. New agents have recently been included in the therapeutic armamentarium, such as gemcitabine, irinotecan, paclitaxel. This fact has allowed many patients to receive a relatively active second line therapy, but the overall survival remains unchanged. Targeted therapies are undergoing some evaluations, but the data are too premature and so far quite discouraging. At the present time there is a urgent need to improve clinical research in this somehow forgotten disease.

Antineoplastic Agents↗
PubMed2005

RT-PCR determination of maspin and mammaglobin B in peripheral blood of healthy donors and breast cancer patients.

BACKGROUND: The aim of the present study was to evaluate the accuracy of two markers, maspin and mammaglobin B, singly or in combination, to detect breast cancer. To define better the potential and limits of the two markers for diagnostic purposes, blood positivity was analyzed in relation to clinical, pathological and biological tumor characteristics. PATIENTS AND METHODS: The markers were determined in peripheral blood (PB) samples from 27 healthy donors and 140 previously untreated patients using nested reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Positivity for maspin in blood samples was observed in 24% of patients with an 89% specificity. For mammaglobin B, positivity was observed in 7% of patients and never in healthy donors. The presence of maspin was correlated with cell proliferation of the primary tumor (P = 0.015), whereas mammaglobin B positivity correlated with pathological stage (P = 0.013). The presence of either marker was significantly related to nodal status. CONCLUSIONS: Our results indicate that the two markers in association could represent a potentially useful non-invasive tool to detect breast cancer. The validation of these markers as indicators of high risk of relapse is ongoing in a series of patients with an adequate follow-up.

Adult↗
PubMed2005

Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours.

We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1-20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31-173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients.

Adolescent↗
PubMed2005

A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.

BACKGROUND: Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy. PATIENTS AND METHODS: Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B). RESULTS: Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04). CONCLUSIONS: The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.

Adolescent↗
PubMed2005

High-dose chemotherapy with autologous haemopoietic support for advanced ovarian cancer in first complete remission: retrospective analysis from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT).

The majority of advanced ovarian cancer patients achieve an objective response following chemotherapy; however, only 20-30% are in remission after 5 years. Intraperitoneal or high-dose chemotherapy (HDC) may prolong disease-free and overall survival (OS) in patients with platinum-sensitive, small volume disease. To better define the subsets of patients who might benefit from HDC, we performed a retrospective analysis on 91 patients in 1st complete remission (CR) treated from 21 centres of the EBMT group. At a median follow-up of 48 months, median time-to-progression (TTP) and OS were 21.2 and 44.4 months, respectively. Tumour grade, stage, residual disease, disease status before HDC, type and year of transplant, source of haemopoietic progenitors and use of haemopoietic growth factors (HGF) after transplant were analysed for TTP and OS. The only significant parameter was the use of HGF: median OS for patients receiving or not receiving HGF was 46.2 vs 17.8 months, respectively (P: 0.035); this difference was maintained after multivariate analysis (P: 0.02). Our analysis does not identify any subgroup of patients in 1st CR who can benefit from HDC; however, median survival of patient with no residual disease has not been reached. The role of HGF after HDC deserves further investigation.

Adolescent↗
PubMed2005

Dual tyrosine kinase inhibitors in chronic myeloid leukemia.

The Bcr-Abl inhibitor imatinib mesylate induces complete hematologic and cytogenetic remissions in most newly diagnosed chronic myeloid leukemia (CML) patients, but relatively few of them achieve molecular remission. In addition, imatinib is much less effective in advanced phase-CML as well as in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL), mainly due to the development of drug resistance. The challenge for the future is to improve current clinical results with kinase inhibitors in CML, developing strategies that can eradicate residual disease and overcome or prevent resistance. 'Dual' Src and Abl kinase inhibitors are an attractive class of compounds, since (a) these molecules are able to bind Bcr-Abl with less stringent conformational requirements with respect to imatinib, therefore allowing for efficient inhibition of several, resistance-associated mutant forms of Bcr-Abl; (b) Src kinases have been shown to be involved in Bcr-Abl-mediated leukemogenesis as well as upregulated in some patients resistant to imatinib. Here, we review the development, the mode of action and the preclinical or early clinical evaluation of several novel dual Src and Abl kinase inhibitors.

Antineoplastic Agents↗
PubMed2005

Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience.

BACKGROUND: Results of second-line chemotherapy in patients with extragonadal non-seminomatous germ cell tumor (NSGCT) appear inferior to results in testicular NSGCT. Patients with retroperitoneal NSGCT achieve a comparable long-term survival rate of 30%, but the salvage rates of patients with mediastinal primary are less than 10%. We conducted a retrospective analysis on patients with mediastinal and retroperitoneal NSGCT treated with second-line high-dose chemotherapy (HDCT) registered with the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS AND METHODS: Between 1987 and 1999, 59 registered patients with retroperitoneal (n=37) and mediastinal (n=22) primary NSGCT, median age 28 years (range 18-60), were treated with second-line HDCT. All had received cisplatin-containing chemotherapy as first-line treatment. RESULTS: Toxic death occurred in three cases (5%). With a median follow-up of 58 months (range 14-114), 18/59 patients (30%) continue to be disease-free. Of three patients who had a disease recurrence after HDCT, one patient achieved a disease-free status with further chemotherapy and surgery. In total, 19 patients (32%) are currently disease-free. Sixteen of 37 patients (43%) with retroperitoneal NSGCT, and three of 22 patients (14%) with mediastinal NSGCT are currently alive and disease-free. CONCLUSIONS: Second-line HDCT might represent a possible option for patients with retroperitoneal primary NSGCT. New salvage strategies are needed for patients with mediastinal NSGCT.

Adolescent↗
PubMed2005

FDG-PET in the management of germ cell tumor.

Germ cell tumor is the most common malignancy in young men. The cure rate of these patients has tremendously increased in the cisplatin era, and recent results have indicated that the management of patients with GCT is still improving. The use of FDG-PET in the management of patients with GCT has been recently investigated. This report attempts to comprehensively review new advances and delineate the potential applications of FDG-PET in GCT.

Adult↗