Biomedical subjects

Giampietro Gasparini

Publications and source records attributed to Giampietro Gasparini.

31 records · Page 2Linked to original sources

PubMed2003

Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. PATIENTS AND METHODS: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. RESULTS: Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. CONCLUSION: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.

Adult↗

PubMed2003

Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial.

BACKGROUND: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test. Secondary endpoints were quality of life and toxicity. RESULTS: Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. CONCLUSION: The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.

Aged↗

PubMed2003

Inhibitors of cyclo-oxygenase 2: a new class of anticancer agents?

Experimental studies have shown that cyclo-oxygenase 2 (COX2) is involved in tumour development and progression. Selective inhibitors of COX2 (coxibs) block tumour growth through many mechanisms, especially by antiangiogenic and proapoptotic effects. In experimental models, coxibs potentiate the activity of cytotoxic agents, hormones, and radiotherapy. Large clinical studies have shown chemopreventive activity of coxibs in colorectal cancer. The findings of preclinical studies coupled with the overexpression of COX2 observed in advanced human tumours are the basis for new therapeutic anticancer strategies based on combinations of coxibs with other anticancer treatment modalities. Early clinical studies have documented the feasibility, good tolerability, and promising activity of coxibs combined with chemotherapy in patients with advanced colorectal and non-small-cell lung cancers. Here, we describe the recent findings on the antitumour effects of coxibs with particular focus on the opportunities that have emerged for treatment of cancer.

Antineoplastic Agents↗

PubMed2003

The combination of gemcitabine and vinorelbine is an active regimen as second-line therapy in patients with metastatic breast cancer pretreated with taxanes and/or anthracyclines: a phase I-II study.

PURPOSE: To evaluate the activity and toxicity of gemcitabine and vinorelbine (GemVin), in patients with advanced breast cancer, previously treated with anthracyclines alone or with taxanes. Patients and methods. Nine patients were entered into the phase I and 50 patients were entered into the phase II study. Gemcitabine was administered beginning with the dose of 800 mg/m2 and vinorelbine was given at the fixed dose of 25 mg/m2, both on days 1 and 8, every 21 days. Escalated dose levels of gemcitabine were planned by increments of 200 mg/m2 per level. The median age of the 50 assessable patients for the phase II study was 56.5 years (range 30-70) and median performance status (PS, ECOG score), 1 (range 0-2). The dominant sites of metastases were viscera in 40, bone in five and soft tissue in five patients. First-line chemotherapy for metastatic disease with taxanes and anthracyclines or with anthracyclines alone was administered in 36 and 14 patients, respectively. RESULTS: The optimal schedule for the combination was gemcitabine 800 mg/m2 and vinorelbine 25 mg/m2. The maximum tolerated dose of gemcitabine was 1000 mg/m2, with grade 4 neutropenia occurring in two cases at this dose level. Overall, 267 cycles were given to the 50 patients enrolled into the phase II (mean 5.3; range 3-9). The schedule was well tolerated: three patients experienced grade 4 neutropenia and another four patients experienced grade 3 anemia. Non-hematological toxicities were moderate. A major objective response was observed in 42% of patients (95% confidence interval (CI), 28-57%), with complete remission in four (8%) and partial response in 17 (34%) patients. The median time to progression was 6 months. Activity as well as toxicity were similar in the subgroups of the patients pretreated either with combinations of taxanes and anthracyclines or anthracyclines alone. CONCLUSIONS: The optimal GemVin schedule is an effective and well tolerated second-line therapy in patients with metastatic breast cancer pre-treated with anthracycline-based schedules or with combinations of anthracyclines and taxanes.

Adult↗

PubMed2003

Thalidomide: a new anticancer drug?

Experimental studies have demonstrated that thalidomide (Thal), a drug developed as a sedative, has antitumoural properties. The possible antitumour mechanisms of action involve: inhibition of angiogenesis, cytokine-mediated pathways, modulation of adhesion molecules, inhibition of cyclooxygenase-2 and stimulation of immuno response. Therefore, Thal is under clinical evaluation in oncology. This paper provides an overview of the data currently available in literature regarding, in terms of activity and toxicity, the use of Thal in cancer patients. Multiple myeloma is so far the most responsive malignancy. A moderate activity has been documented in certain solid tumours: glioblastoma multiforme, renal cell carcinoma and malignant melanoma. Tolerability is generally satisfactory with peripheral neuropathy being the most relevant dose-dependent toxicity. The more frequent, but moderate side effects are: somnolence, constipation, dizziness and fatigue. More studies are needed to properly evaluate the anticancer activity of Thal alone or in combination with other anticancer treatments. Preliminary studies suggest promising results of Thal in combinations with corticosteroids and cytotoxic drugs as front-line therapy of multiple myeloma. Regarding therapy of solid tumours in the adult, combination with chemotherapy, radiation therapy and molecular-targeting compounds are under investigation.

Animals↗

PubMed2003

Prognostic and predictive indicators in operable breast cancer.

Because of its biological heterogeneity and wide spectrum of responsiveness to different treatments, breast cancer is a complex disease of difficult clinical management. Over the past several years, knowledge of the molecular mechanisms regulating normal and aberrant cell growth leading to cancer has been enhanced. These advances have enabled the identification of an increasing number of surrogate biomarkers, which have been correlated with prognosis or used as predictors of response to specific treatments. Axillary nodal status, age, tumor size, pathologic grade, and hormone receptor status are the established prognostic and/or predictive factors for selection of adjuvant treatments. The role of new biomarkers, such as p53, HER2/neu, angiogenesis, and the proliferation index value, is promising; however, the clinical value of their determination must be provided by prospective clinical studies.

Breast Neoplasms↗

PubMed2002

[Innovative treatment in oncology].

The improved knowledge of the key molecular mechanisms involved in cell transformation and tumor progression allows to the identification of new therapeutic targets for anticancer therapy. Several molecular-targeting compounds have been developed, capable to selectively interfire with tumorangiogenesis, receptors with tyrosin-chinase activity, specific tumor growth factors. A rationale selection of the patients as well as an appropriate monitoring of pharmacodynamics effects of molecular-targeting compounds need of the availability of surrogate markers, assessable in tumor tissue of circulating blood.

Antibodies, Monoclonal↗

PubMedDate not supplied

Tailored therapy of colorectal cancer: results, challenges and future directions.

Colorectal cancer is a leading cause of cancer mortality and morbidity. Despite the recent results of systemic chemotherapy, more than 40% of patients with advanced cancer still do not achieve substantial benefits with cytotoxic agents. Therefore, new tailored strategies are warranted to improve the probability of disease control. The rationale for this approach is based on the identification of the in vivo interactions among patient's characteristics, disease physiopathology, and drug pharmacodynamics and pharmacokinetics. Genomic and proteomic technologies may clarify the mechanisms involved in cancer growth and progression in each single patient and in the molecular basis of interindividual differences of anticancer drugs in terms of efficacy and toxicity. Despite the recent encouraging data, the clinical use of targeted therapy is hampered by several questions, such as: optimal biologic dose and schedule, lack of predictive surrogate biomarkers, and modalities of combination with chemotherapy/radiotherapy. Further efforts are needed to improve the reliability of genomic and proteomic technologies, in particular regarding their standardization and widespread availability. These unsolved issues make tailored therapy an open challenge.

Adult↗

PubMedDate not supplied

The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for non-small cell lung cancer: a phase II study with biological correlates.

PURPOSE: The selection of effective schedules of treatment for metastatic non-small cell lung cancer still remains a challenge for the oncologist. The present multicentric phase II study was designed in order to investigate the activity and safety of the combination of weekly paclitaxel and celecoxib as second-line treatment for non-small cell lung cancer. As a secondary endpoint, the possible correlation of biomarkers with objective response was investigated in a subset of patients. PATIENTS AND METHODS: Patients with platinum-refractory non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0-2 entered the present phase II study. Paclitaxel was administered at the dose of 80 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week rest, and celecoxib, 400 mg p.o. b.i.d. administered continuously. A cycle consisted of 8 weeks of treatment. Determination of circulating vascular endothelial growth factor and interleukin 6 was performed at baseline and every two cycles. RESULTS: Fifty-eight patients were enrolled: median age, 60 years (range, 30-77 years); male/female ratio = 44/14; performance status, 0, 31 patients; 1, 25 patients; and 2, two patients. Predominant histotype was adenocarcinoma (34 cases), and most patients had at least two sites of disease. According to the intent-to-treat analysis, 14/58 objective responses (24.1%) and 24/58 (41.3%) stabilizations of disease were observed, with a median duration of 4 months (range, 2-22+ months) and 5 months (range, 1-13 months), respectively. Median time to progression and median overall survival were 5 and 11 months, respectively. One-year survival was 42.5%. The main toxicity was neuropathy (4% of grade 3). Preliminary results suggest that decrease in serum vascular endothelial growth factor level is significantly associated with clinical response. DISCUSSION: Combination of celecoxib and weekly paclitaxel is safe and active new regimen in pretreated non-small cell lung cancer. Toxicity appears not to be worsened by the addition of celecoxib. According to preliminary results, serum vascular endothelial growth factor level seems to be predictive of response, suggesting that it should be further investigated as a surrogate marker of response.

Administration, Oral↗

PubMedDate not supplied

Thalidomide is inactive in heavily pretreated patients with metastatic breast cancer.

Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. We investigated the therapeutic activity and toxicity of thalidomide in patients with progressive metastatic breast cancer pretreated with chemotherapy. Inclusion criteria were metastatic breast cancer in progression of disease after at least two lines of chemotherapy, age > or = 18 years, performance status < or = 2, and adequate hematologic, renal, and hepatic functions. Twelve patients entered the study, eight of whom were pretreated with three or more lines of chemotherapy (66.7%). Thalidomide was well tolerated: the most common side effects were constipation and somnolence (58.3% of patients). No objective response or durable stable disease was observed. Median time to progression and median overall survival were 8 weeks (range, 4-10 weeks) and 16 weeks (range, 8-54 weeks), respectively. In conclusion, thalidomide is an ineffective treatment in patients with progressive metastatic breast cancer heavily pretreated with chemotherapy.

Adult↗

PubMedDate not supplied

An unusual case of three synchronous tumors in a young woman.

The occurrence in the same young patient of three synchronous tumors deriving from different embryogenic tissues and without a clear correlation with a common etiopathogenic factor is very unusual. We report a case of a Caucasian woman submitted to wide resection of a large retroperitoneal liposarcoma and right radical nephrectomy for suspected tumor infiltration. Histological examination of the right ureter and renal pelvis showed the presence of a multifocal urothelial carcinoma that was clinically asymptomatic. Two months later, during follow-up, chest X-ray and computed tomography documented a coin lesion of the upper left lung, confirmed by positron emission tomography. This nodule was surgically removed and examined histologically, resulting in a diagnosis of sclerosing hemangioma. The patient is alive without evidence of recurrent disease.

Female↗

PubMedDate not supplied

Antiangiogenic agents.

Explore the source record for details and available documents.

Angiogenesis Inhibitors↗

PubMedDate not supplied

Comparing the efficacy and safety of fixed versus weight-based dosing of epoetin alpha in anemic cancer patients receiving platinum-based chemotherapy.

Fixed dosing is potentially more convenient than weight-based dosing for both patients and physicians. Therefore, this open-label, randomized (1:1), multicenter study was conducted to compare the effectiveness, safety, and quality-of-life benefits of fixed vs. weight-based dosing of epoetin alpha in anemic cancer patients undergoing chemotherapy. Five hundred forty-six anemic patients undergoing platinum-based chemotherapy for solid malignancies were enrolled. Patients received epoetin alpha, either a fixed dose of 10,000 IU or a weight-based dose of 150 IU/kg, administered subcutaneously 3 times weekly for up to 12 weeks. Endpoints were transfusion requirements over days 29-84, change in hemoglobin (Hb) level from baseline, and change in quality-of-life (QOL) scores from baseline as measured using the Cancer Linear Analog Scale (CLAS). Five hundred and thirty-two patients received at least 1 dose of epoetin alpha, and 510 of these (255 in each treatment group) were considered evaluable for efficacy. At day 84, rates for freedom from transfusion were similar between the fixed-dose and the weight-based dose group (84% vs. 87%, respectively, p=0.32), as calculated by the lifetable method. These rates were also similar between patients in the 45-63 kg weight group receiving the fixed 10,000 IU dose or 7,000-9,000 IU on a per-weight basis (83% vs. 87%, respectively), and those in the 70-100 kg weight group receiving the fixed 10,000 IU dose or 11,000-15,000 IU on a per-weight basis (85% vs. 83%, respectively). Mean Hb increases from baseline to last observation were 2.10 g/dl [95% confidence intervals (CI95) 1.85-2.35] in the 10,000 IU group (from 9.64-11.74 g/dl) and 2.06 g/dl (CI95 1.82-2.30) in the 150 IU/kg group (from 9.70-11.76 g/dl). QOL results were similar for both groups and cumulative data have been reported. For 275 patients (in both groups combined) with CLAS QOL scores both at baseline and 29-98 days thereafter, the QOL index (average of scores for the 3 QOL parameters: energy level, ability to do daily activities and overall QOL) increased by 10.4 mm (CI95 7.5-13.2), from 46.2 mm at baseline to 56.6 mm at the final observation. QOL improvements were directly associated with Hb increases (p<0.001, multiple linear regression analysis) within all chemotherapy response classes. Epoetin alpha was well tolerated in both groups. Fixed (10,000 IU) and weight-based (150 IU/kg) dosing regimens of epoetin alpha demonstrated similar efficacy in maintaining freedom from transfusion, increasing Hb levels, and improving QOL in anemic cancer patients undergoing platinum-based chemotherapy. QOL improvements were directly associated with Hb increases. These findings support the use of a fixed-dose regimen of epoetin alpha, which may offer greater convenience for physicians and patients than weight-based dosing with this agent.

Adult↗