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Cesare Gridelli

Publications and source records attributed to Cesare Gridelli.

At least 19 recordsLinked to original sources
PubMed2007

The use of bisphosphonates in elderly cancer patients.

As life expectancy increases throughout the 21st century, the size of the elderly population will also expand. This will have a marked effect on the number of patients with cancer who are classified as elderly. Despite this, the design of most clinical studies of cancer therapies excludes those patients who are > or =70 years of age. Bisphosphonates are an example of a cancer therapy that has not been examined in randomized clinical trials of elderly patients. These agents are used for the prevention of skeletal complications and the relief of bone pain in patients with bone metastases. When deciding which bisphosphonate to prescribe to an elderly patient, each drug should be considered on its individual merits. Examples of areas of concern with bisphosphonates in elderly patients include their relative renal safety profiles and propensity for osteonecrosis of the jaw. Another consideration when choosing the most appropriate formulation is the preferred method of administration (oral or i.v.), which may affect patient compliance with therapy. As the use of bisphosphonates increases, the need for data on their use in elderly patients also becomes greater. Clinical trials of bisphosphonates in this patient population are currently under way, and their results are keenly awaited.

Aged↗
PubMed2006

Cetuximab in advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains a major problem in the western civilization and developing countries. Since most patients with NSCLC have advanced disease at diagnosis, to date, chemotherapy, with third-generation platinum-based doublets, represents the standard of care. Advances in the knowledge of tumour biology and mechanisms of oncogenesis has granted the singling out of several molecular targets for NSCLC treatment. Epidermal growth factor receptor (EGFR), a member of ErbB family, is one of the most studied target. Cetuximab is a chimeric (human-murine) monoclonal antibody directed against the extracellular domain of the EGFR that blocks ligand (TGF-alpha, EGF) access to the receptor. In the present paper we discuss about the activity, tolerability and efficacy of cetuximab, the EGFR monoclonal blocking antibody with the largest amount of clinical data being available on the treatment of advanced NSCLC.

Antibodies, Monoclonal↗
PubMed2006

Antiangiogenic drugs in non-small cell lung cancer treatment.

PURPOSE OF REVIEW: A promising therapeutic target is the vascular endothelial growth factor pathway - a key mediator of tumor angiogenesis - which is important in tumor growth, invasion, and metastasis. This review focuses on the available clinical data on drugs targeting the vascular endothelial growth factor - vascular endothelial growth factor receptor pathway in the treatment of non-small cell lung cancer. RECENT FINDINGS: The therapeutic value of inhibiting the vascular endothelial growth factor pathway has been demonstrated by using drugs that prevent vascular endothelial growth factor receptor binding and by using drugs that inhibit receptor activation. Two antiangiogenic drugs exemplify these mechanisms: bevacizumab (Avastin; Genentech, South San Francisco, California, USA), a humanized monoclonal antibody that acts by binding and neutralizing vascular endothelial growth factor; and ZD6474 (Zactima; AstraZeneca, Macclesfield, UK), a small-molecule inhibitor of vascular growth factor receptor and epidermal growth factor receptor tyrosine kinase activity. Recently, the first results of a large, phase III randomized clinical trial of bevacizumab in combination with platinum-based doublet chemotherapy have been reported in patients with nonsquamous non-small cell lung cancer. SUMMARY: The inhibition of tumor angiogenesis is a key therapeutic strategy that holds great promise for the advancement of metastatic lung cancer therapy. The combination of bevacizumab and conventional chemotherapy could offer a new therapeutic option in selected non-small cell lung cancer histotypes.

Angiogenesis Inhibitors↗
PubMed2006

Combining targeted therapies and drugs with multiple targets in the treatment of NSCLC.

The first generation of clinical trials of targeted agents in non-small cell lung cancer (NSCLC) treatment has concluded. To date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease. Nevertheless, clinically meaningful advances have already been achieved. In chemotherapy-refractory advanced NSCLC patients, gefitinib and erlotinib, two epidermal growth factor receptor tyrosine kinase inhibitors, represent a further chance for tumor control and symptom palliation. In chemotherapy-naive, advanced, nonsquamous NSCLC patients, the combination of the anti-vascular endothelial growth factor monoclonal antibody bevacizumab with chemotherapy was demonstrated to produce better survival outcomes than with chemotherapy alone. The relative failure of first-generation targeted therapies in lung cancer may be a result of multilevel cross-stimulation among the targets of the new biological agents. Thus, blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Preclinical evidence of the synergistic antitumor activity achievable by combining targeted agents that block multiple signaling pathways has recently been emerging. Clinical trials of multitargeted therapy may represent the second generation of studies in this field, and some of these are already ongoing. In a recent phase I/II trial, the combination of erlotinib and bevacizumab demonstrated very promising activity in the treatment of advanced NSCLC pretreated with chemotherapy. Whether the multitargeted approach is best performed using combinations of selective agents or agents that intrinsically target various targets is a matter of debate.

Animals↗
PubMed2006

Treatment of stage I-III non-small-cell lung cancer in the elderly.

Elderly patients with stage I-III non-small-cell lung cancer (NSCLC) constitute a peculiar patient population and need specific therapeutic approaches. Limited resections are an attractive alternative for elderly patients with resectable NSCLC because of the potential reduction in postoperative complications. Curative radiation therapy is an acceptable alternative for elderly patients who are unfit for or refuse surgery. Hypofractionated stereotactic body radiation therapy is of particular interest for this population because of its favorable tolerance. Elderly patients may tolerate chemotherapy poorly because of comorbidity and organ failure. The survival benefit obtained with adjuvant platinum-based chemotherapy in the younger population may vanish or decrease in the elderly because of a potential higher toxic death rate or lower compliance to treatment. The efficacy and feasibility of adjuvant chemotherapy for elderly patients need to be investigated in specific trials. Neoadjuvant chemotherapy remains an experimental approach under investigation in the general patient population, and consequently should not be considered in clinical practice in the elderly. Retrospective analyses on chemoradiation in elderly patients should be considered globally ambiguous and at risk of selection bias. Only specifically designed prospective studies will elucidate the real role and feasibility of this combined approach in the treatment of unselected elderly patients.

Age Factors↗
PubMed2005

Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.

PURPOSE: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. PATIENTS AND METHODS: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. RESULTS: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. CONCLUSIONS: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Activities of Daily Living↗
PubMed2005

Screening for lung cancer: New horizons?

Lung cancer remains the leading cause of cancer-related deaths in the world. At present, the only high rate of cure therapy is surgical resection at early stage of disease. Early detection could potentially decrease lung cancer mortality suggesting that this cancer should be a good candidate for screening. Results of trials involving chest X-ray, sputum cytology and low-dose computed tomography (CT) are discussed here. The latter tool offers advantages over chest X-ray, but final results from controlled well conducted trials are necessary before the real utility of CT mass screening can be determined. Further approaches to secondary prevention such as screening with positron emission tomography (PET), autofluorescence bronchoscopy and biomarkers hold great promise for the future.

Age Factors↗
PubMed2005

Treatment of advanced non-small-cell lung cancer in the elderly: results of an international expert panel.

The best treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) is still debated. To guide clinical management of these patients and suggest the priorities for clinical research in this field, an International Expert Panel met in Naples, Italy, on April 19 to 20, 2004. Results and conclusions based on a review of evidence available in the literature to date are presented in this article. A comprehensive geriatric assessment is recommended to better define prognosis and to predict tolerance to treatment. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. These data should be interpreted cautiously because retrospective subgroup analyses are encumbered by selection bias; hence, randomized trials dedicated to platinum-based chemotherapy for nonselected elderly patients are warranted. Several promising biologic therapies are under investigation; however, with present data, target-based agents as first-line treatment for elderly NSCLC patients are not yet recommended. Clinical research, with trials specifically designed for elderly patients, is mandatory. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, a taxane) should be the recommended option for nonselected elderly patients with advanced NSCLC. Platinum-based chemotherapy is a viable option for fit patients with adequate organ function. Best supportive care remains important, in addition to chemotherapy or as the exclusive option for patients who are unsuitable for more aggressive treatment.

Age Factors↗
PubMed2005

A multicenter, randomized, Phase II study of cisplatin, etoposide, and gemcitabine or cisplatin plus gemcitabine as first-line treatment in patients with poor-prognosis small cell lung carcinoma.

BACKGROUND: The objective of this study was to evaluate the activity and toxicity of combined cisplatin, etoposide, and gemcitabine (PEG) and combined cisplatin plus gemcitabine (PG) in previously untreated patients with extensive-stage and poor-prognosis limited-stage small-cell lung carcinoma. METHODS: One hundred forty patients (70 patients in two arms) were randomized to receive either cisplatin 70 mg/m2 on Day 1, etoposide 50 mg/m2 on Days 1-3, and gemcitabine 1000 mg/m2 on Days 1 and 8 or cisplatin 70 mg/m2 on Day 1 plus gemcitabine 1250 mg/m2 on Days 1 and 8. Both regimens were recycled every 21 days. RESULTS: In total, 626 cycles were delivered (303 cycles of PEG and 323 cycles of PG), with a median of 4 cycles per patient in both arms. The objective response rate was 63% (95% confidence interval [95%CI], 49-71%) for PEG and 57% (95%CI, 43-67%) for PG, with the suggestion of a higher complete response rate in the PEG arm (18.6% and 4.3%, respectively). A similar time to disease progression (6 months in the PEG arm and 7 months in the PG arm) and a similar median survival (9.5 months in the PEG arm and 10 months in the PG arm) were observed in both arms. The PEG regimen was associated with more severe hematologic toxicity in terms of neutropenia, febrile neutropenia, and a higher rate of treatment delays and dose reductions, whereas nonhematologic toxicities did not differ between the two arms. CONCLUSIONS: According to the results of this Phase II randomized trial, the PEG regimen produced a higher complete response rate but more toxicity compared with the PG regimen in patients with extensive-stage or poor-prognosis, limited-stage small cell lung carcinoma.

Aged↗
PubMed2005

Trying to compose the puzzle with all the pieces: epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.

Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown promising activity in patients with non-small cell lung cancer (NSCLC). Gefitinib has been the first of these drugs to be licensed for third-line treatment of advanced NSCLC patients. More recently, erlotinib has been shown to be more effective than placebo in increasing overall survival (OAS) and has been approved for NSCLC patients after failure of chemotherapy. However, a large body of clinical and experimental evidence suggests that the benefit from these drugs is limited to a subgroup of patients. The availability of clinical or molecular criteria for predicting sensitivity to EGFR-TKIs is the most relevant issue for their correct use and for planning future research. Determination of EGFR expression is not sufficient to predict sensitivity to EGFR-TKIs. However, several clinical features (female gender, adenocarcinoma/bronchioloalveolar histotype, never-smoking status, Oriental Asian origin) are associated with major clinical responses. The identification of somatic mutations in the tyrosine kinase domain of the EGFR gene represents the most important molecular marker of sensitivity to EGFR-TKIs. These "activating" mutations can be found in a high proportion of gefitinib- or erlotinib-responding patients. However, clinical effectiveness might not be limited to patients carrying EGFR mutations, in which the objective response is probably the detectable effect of apoptosis induction in cancer cells. In fact, clinical efficacy with gefitinib or erlotinib is also observed in another subgroup of patients, in which a tumor growth delay, determined by a block in cancer cell proliferation, could induce a prolonged and clinically relevant disease stabilization.

Animals↗
PubMed2005

Safety profile of gefitinib in advanced non-small cell lung cancer elderly patients with chronic renal failure: two clinical cases.

OBJECTIVES: Comorbidities often contraindicate any chemotherapy in non-small cell lung cancer (NSCLC) patients, even single-agent one. This is the case of chronic renal failure. METHODS: Two elderly patients (age >70 years) affected by advanced non-small cell lung cancer and chronic renal failure were treated, as front-line treatment, with gefitinib (ZD1839--'Iressa') administered orally at the dose of 250 mg daily. RESULTS: In both patients renal function was not impaired by the treatment with gefitinib and no severe toxicity was recorded. One patient reported a stable disease, lasted 141 days, with symptoms relief. In the other patient a mixed response was reported with one large pulmonary site responding to gefitinib, but with appearance of new small lung metastases. He is still alive at 359 days. CONCLUSIONS: Gefitinib resulted safety when administered to advanced NSCLC elderly patients affected by chronic renal failure. Gefitinib should be further evaluated as front-line treatment in a larger sample of such patients, in order to establish a therapeutic option for a sort of patients unsuitable for any chemotherapy.

Administration, Oral↗
PubMed2005

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials.

BACKGROUND: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. METHODS: We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival. FINDINGS: In the landmark group, hazard ratios of death were 0.65 (0.46-0.93) for patients with severe neutropenia and 0.74 (0.56-0.98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31.4 weeks (95% CI 25.7-39.6) for patients without neutropenia compared with 42.0 weeks (32.7-59.7) for patients with severe neutropenia, and with 43.7 weeks (36.6-66.0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0.0118). Findings were much the same for the out-of-landmark group. INTERPRETATION: Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.

Adult↗
PubMed2005

Chemotherapy for elderly patients with non-small cell lung cancer: a review of the evidence.

Chemotherapy for elderly patients with non-small cell lung cancer (NSCLC) has been questioned due to the perceived potential for higher toxicity in this population, possibly attributable to progressive organ failure and comorbidities. This non-systematic review presents the authors' selection of key evidence for the use of chemotherapy for elderly patients with NSCLC. To date, single-agent chemotherapy with agents such as vinorelbine, gemcitabine, docetaxel, and paclitaxel has been a reasonable option. Data on non-platinum-based combinations are limited, but recent investigations of gemcitabine plus vinorelbine failed to show superiority over either agent alone. Retrospective subset analyses from large randomized trials suggest that the efficacy and tolerability of platinum-based combination chemotherapy are similar in both the elderly and their younger counterparts. Further phase III trials that specifically examine platinum-based combinations in selected elderly NSCLC patients are therefore warranted. The potential impact of new targeted therapies-alone or in combination with chemotherapy-is being investigated.

Aged↗
PubMed2005

Safety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients.

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed at > 65 years of age and approximately one-third of all patients are > 70 years of age. Elderly patients tolerate chemotherapy poorly compared with their younger counterpart because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive platinum-based chemotherapy, the standard medical treatment for advanced NSCLC. In clinical practice, single-agent chemotherapy should remain the standard treatment. Feasibility of platinum-based chemotherapy remains an open issue and has to be proven prospectively. Moreover, a multidimensional geriatric assessment for individualised treatment choice in NSCLC elderly patients is mandatory. This review focuses on the currently-available evidences for the treatment of elderly patients affected by advanced NSCLC with regards to the role and safety of platinum-based chemotherapy.

Age Factors↗