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Biomedical subjects

C Gridelli

Publications and source records attributed to C Gridelli.

At least 37 records · Page 2Linked to original sources
PubMed2003

Lessons from the ("Iressa" Expanded Access Programme: gefitinib in special non-small-cell lung cancer patient populations.

Some subgroups of patients with advanced/metastatic non-small-cell lung cancer (NSCLC) are frequently considered ineligible for the aggressive, platinum-based combination chemotherapy that is the recommended treatment. Elderly patients may have a poorer tolerance of chemotherapy due to impaired organ function and frequent comorbidities; patients with poor performance status (PS; > or =2 due to NSCLC and/or coexisting illnesses) are often considered unfit for chemotherapy; other patients may be unable or unwilling to endure the toxicity or inconvenience of chemotherapy. These patient groups may benefit from novel, relatively nontoxic treatment modalities. Gefitinib ("Iressa", ZD1839) 250 mg day(-1) is well tolerated and has proven antitumour and symptom improvement activity in patients with previously treated NSCLC. Phase II trials (IDEAL 1 and 2) of gefitinib in advanced/metastatic NSCLC included 70 out of 425 (16.5%) patients with PS > or =2, and their response rate, clinical benefit rate and rates of adverse events were similar to those of the overall trial population. In addition, many patients with advanced/metastatic NSCLC with poor PS or advanced age have received gefitinib 250 mg day(-1) in an Expanded Access Programme (EAP). Observations from the EAP support those of IDEAL 1 and 2, and indicate that gefitinib 250 mg day(-1) warrants further investigation in these patient groups.

Adult↗
PubMed2002

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm). RESULTS: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05). CONCLUSION: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.

Adult↗
PubMed2002

Management of small-cell lung cancer in the elderly.

More than 50% of lung cancer patients are diagnosed over the age of 65 and about 30% over 70. Small-cell lung cancer (SCLC) accounts for 20-25% of lung carcinomas. Chemotherapy is the cornerstone of treatment for SCLC. Usually in the elderly it is difficult to administer the same chemotherapy administered to younger patients because elderly patients tolerate chemotherapy poorly. The empirical reduction of drug doses may be criticized. The best approach is to design specific trials in order to develop active and well-tolerated chemotherapy regimens for SCLC elderly patients. The standard therapy in limited disease is combined chemo-radiotherapy followed by prophylactic brain irradiation for patients achieving a complete response. In the elderly, the addition of radiotherapy to chemotherapy must be accurately evaluated, considering the slight survival improvement and the potential relevant toxicity.

Age Factors↗
PubMed2002

Selective cyclooxygenase-2 inhibitors and non-small cell lung cancer.

Lung cancer is the leading cause of death from cancer in most developed nations. The most common type of lung cancer is of non-small cell histology, representing approximately 80% of the total. Despite aggressive treatments in early stages and improvement of polychemotherapy outcomes in advanced disease, the five years survival rate for lung cancer remains under 15%. Fortunately, our improved knowledge of tumor biology and mechanisms of oncogenesis suggests several new potential targets for clinical research in cancer therapy. A substantial body of evidence indicates that cyclooxigenase (COX)-2 and prostaglandins (PGs) play an important role in tumorigenesis. Mechanisms involved in COX-2 participation in tumorigenesis and tumor growth include xenobiotic metabolism, angiogenesis stimulation, inhibition of immune surveillance and inhibition of apoptosis. COX-2 is frequently overexpressed in bronchial premalignancy, lung adenocarcinoma and squamous cell carcinoma and COX-2 overexpression is a marker of poor prognosis in surgically resected stage I non-small cell lung cancer. Treatment with COX-2 inhibitors reduces the growth of NSCLC cells in vitro and in xenograft studies. Recent studies have defined some of the mechanisms involved in COX-2 participation in NSCLC development and diffusion. These evidences support the hypothesis that selective COX-2 inhibitors (coxibs) may prove beneficial in the prevention and treatment of NSCLC.

Animals↗
PubMed2002

Chemotherapy of 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 over the age of 65 and approximately one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly as compared to their younger counterparts, 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 cisplatin-based chemotherapy, the standard medical treatment of advanced NSCLC. At present, for early stages of the disease there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems to determine no survival advantage as compared to the radiation therapy alone. In advanced disease, single agent vinorelbine has proven to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps even the quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The two main research-lines to be explored in the near future are the introduction of biological agents in the treatment schemes and the development of specifically designed schedules of cisplatin-based regimens. However, practicing a multidimensional geriatric awsessment for individualized treatment choice in NSCLC elderly patients is mandatory.

Age Factors↗
PubMed2001

Carboplatin plus paclitaxel in extensive small cell lung cancer: a multicentre phase 2 study.

A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m(2)3-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial was the objective response rate. 31 objective responses among 50 patients were considered necessary to proceed to a phase 3 trial. 48 patients were enrolled (median age 59 years). Treatment was very well tolerated. 3 patients (6.2%) had a complete response and 23 (47.9%) a partial response, for an overall response rate of 54.2% (95% CI: 39.2-68.6). Median time to progression was 5.7 months (95% CI: 5.2-6.2). Median survival was 9.6 months (95% CI: 7.2-14.6), with a median follow-up time of alive patients of 12 months. At 1 year, the probability of being progression-free or alive was 0.16 and 0.43, respectively. In conclusion, carboplatin plus paclitaxel as given in the present study is very well tolerated but not sufficiently active to warrant phase 3 comparison with standard chemotherapy regimens.

Adult↗
PubMed2001

Quality of life in lung cancer patients.

The quality of life of lung cancer patients is affected by several factors related to the patients, stage of disease and treatment characteristics. For small-cell lung cancer (SCLC), the treatment is generally aggressive, primarily based on chemotherapy. Treatment strategy for non-small-cell lung cancer (NSCLC) is strongly dependent on the stage of the disease and ranges from surgery to palliative chemotherapy. Over the last few years, very little progress has been made in terms of survival. Therefore, the effect of treatment on quality of life has become progressively more relevant. Among the instruments for measuring quality of life, there are some specifically developed for lung cancer, such as the European Organization for Research and Treatment of Cancer (EORTC) LC-13 questionnaire, the Functional Assessment of Cancer Therapy (FACT-L) questionnaire and the Lung Cancer Symptom Scale (LCSS). Up to now, few randomised clinical trials have correctly evaluated quality of life. There are evident pitfalls associated with the use of frequently non-validated tools, and poor methods of data analysis, but quality-of-life evaluation is crucial and should be addressed through well-planned and well-conducted prospective clinical trials.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Ischemic colitis associated with paclitaxel.

Systemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. This report describes the case of a 49-year-old woman with liver metastases from a neuroendocrine tumor of unknown origin who developed mild ischemic colitis after chemotherapy with carboplatin and paclitaxel. The patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea, which resolved in about 10 days. She had a normal white blood cell count throughout her illness; the assay of stool specimens for Clostridium difficile toxins and the stool cultures were both negative. A sigmoidoscopy showed a mild, transient ischemic colitis, which was confirmed by pathologic examination of the biopsy specimens. Although carboplatin is not related to severe colonic cytotoxicity, it has been previously reported that paclitaxel induces necrosis of the gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is the most frequent complication in patients with cancer who undergo paclitaxel-based chemotherapy and develop gastrointestinal toxicity. Once C. difficile infection has been excluded, a diagnosis of ischemic colitis should be considered, especially in patients with cancer who have normal white blood cell counts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study.

In a phase III trial, 191 patients aged over 70 with stage IIIB/IV non-small cell lung cancer were randomized to receive best supportive care (BSC) alone or BSC plus vinorelbine on days 1 and 8, q 21 days for up to six cycles. Increasing difficulties in recruitment meant that the investigators, blinded to the results, stopped the trial early. Data from 161 patients have been analyzed. The vinorelbine regimen was well tolerated. Grade 3/4 neutropenia occurred in 10% of patients and grade 2/3 anemia in 16%. The principle nonhematological toxicities were constipation and fatigue. An objective response rate was recorded in 19.7% of the 76 patients treated with vinorelbine. The survival experience of these patients was significantly superior to that among control patients. The median duration of survival was longer (28 versus 21 weeks) and patients receiving vinorelbine were significantly more likely to survive to one year (32% versus 14%). The relative risk of death in the vinorelbine group was 0.65 (95% confidence interval: 0.45-0.93). Quality of life was extensively investigated using European Organization for Research and Treatment of Cancer scales. While aspects of quality-of-life issues that were directly related to drug toxicity (such as nausea and constipation) were lower in the vinorelbine group, patients who received vinorelbine fared better than controls on measures related to lung cancer symptoms and pain and on social, cognitive, and physical functioning.

Age Factors↗
PubMed2000

The potential role of amifostine in the treatment of non small cell lung cancer.

Amifostine protects healthy tissues but not tumor cells from the damage induced by cytotoxic treatments, particularly ionizing radiations, alkylating and platinating agents. The clinical effectiveness of amifostine has been demonstrated by randomized trials in ovarian and head-and-neck cancer patients treated with chemotherapy with or without radiation therapy. The available pharmacoeconomic data confirm a favorable cost/utility ratio. The majority of non small cell lung cancer (NSCLC) patients receive radio and/or chemotherapy. A role for amifostine in these patients has been hypothesized, and some experiences performed. The aim of this paper is to outline the present role of amifostine in the treatment of NSCLC.

Amifostine↗
PubMed2000

Thoracic radiotherapy and daily vinorelbine as radiosensitizer in locally advanced non small cell lung cancer: a phase I study.

Experimental studies have shown that vinorelbine is a powerful radiosensitizer in vitro. To date, no reports on clinical activity of the single agent vinorelbine as radiosensitizer have been published. The aim of the present phase I study was to determine the maximum tolerated dose (MTD) of vinorelbine administered daily concurrently with thoracic radiotherapy, with or without amifostine support, in the treatment of locally advanced non small cell lung cancer. In vitro studies have shown that vinorelbine can potentiate the antitumor effects of radiation therapy. Amifostine is a sulphydril compound that has shown to protect normal tissues from chemotherapy and radiotherapy-induced toxicities. Radiotherapy lasted 6 weeks and the total dose was 55 Gy. The daily fraction was 1.8 Gy, administered 5 days a week for 5 weeks and increased to 2.0 Gy during the sixth and last week. Concurrent vinorelbine was administered daily with a planned escalation of the dose from 4, to 5 and 6 mg/m(2). Fourteen patients were enrolled in the study. The first dose of vinorelbine was 4 mg/m(2) and it showed to be feasible without dose-limiting toxicity (DLT). Instead, the second dose level of 5 mg/m(2) was unfeasible because three out of six patients had DLT (grade 4 neutropenia, treatment interruption longer than 2 weeks for prolonged grade 2 neutropenia and treatment interruption longer than 2 weeks for prolonged grade 3 esophagitis together with grade 4 dyspnea). At that time, the study continued adding amifostine to vinorelbine in order to increase its MTD. Amifostine was administered by means of subcutaneous injection 15 min before each radiotherapy fraction at the fixed dose of 300 mg/m(2). However, 5 mg/m(2) of vinorelbine were considered unfeasible even with amifostine support because three out of five patients showed DLT (grade 4 neutropenia, febrile grade 4 neutropenia and grade 3 liver toxicity). Among 14 patients enrolled in the study, eight completed the planned treatment because six patients experienced DLT, which determined treatment interruption. Overall, four partial and two complete responses were observed. Two partial and one complete response were observed in those three patients who had been treated with the first dose of vinorelbine. In conclusion, our data show that the MTD of daily vinorelbine is 4 mg/m(2). Therefore, this is the recommended dose of daily vinorelbine to be administered with concurrent thoracic radiotherapy in a phase II trial. Finally, amifostine administered subcutaneously failed to increase the MTD of daily vinorelbine.

Adenocarcinoma↗
PubMed2000

Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study.

PURPOSE: to evaluate the activity and toxicity of the combination cisplatin plus vinorelbine plus amifostine in advanced non small cell lung cancer (NSCLC). PATIENTS AND METHODS: a two-stage Simon design was applied. To proceed after the first stage, responses from seven of 19 patients were needed. Overall, 17 responses from 40 treated patients were required to comply with the design parameter. Inclusion criteria were cyto-histologically proven stage IIIB-IV NSCLC; age of 70 years or less; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; normal cardiac, hepatic, renal and bone marrow functions; and no previous chemotherapy. Patients were staged by physical examination, biochemistry, chest radiograph, brain, thoracic and abdominal computed tomographic (CT) scans, and bone scan. All patients received cisplatin 100 mg/m(2) intravenously (iv) day 1, vinorelbine 25 mg/m(2) iv days 1-8-15-22, amifostine 740 mg/m(2) iv day 1 every 4 weeks up to six cycles. Eleven of 40 enrolled patients were stage IIIB and 29 stage IV, with a median age of 57 years (range, 38-70 years). RESULTS: all patients were evaluable for response and toxicity (intention to treat analysis). We observed 20 (50%) objective responses, with four (10%) complete responses. Median time to progression was 20 weeks, and median survival was 45 weeks. The toxicity was manageable. The reported main toxicities were neutropenia grade 4 in 10% of patients, grade 1 and grade 3 nephrotoxicity both in 5% of patients and grade 1 amifostine-related hypotension in 15% of patients. CONCLUSION: these data show that cisplatin plus vinorelbine plus amifostine is an active and feaseable regimen in stage IIIB-IV NSCLC. A phase III trial comparing cisplatin plus vinorelbine versus cisplatin plus vinorelbine plus amifostine in advanced NSCLC is warranted.

Adult↗
PubMed2000

Originality, benefits and difficulties of clinical research performed by cooperative groups: the experience of an Italian Lung Cancer Study Group.

In the past years, clinical research performed by cooperative groups achieved important results. The trials of adjuvant chemotherapy in breast and colorectal cancer or neoadjuvant treatment in osteosarcoma are cornerstones in the history of medical oncology and highlight the importance of research performed by cooperative groups. However, there are many difficulties for the functioning of cooperative groups: financial support, slow enrollment of patients in clinical trials, insurance related problems and quality control of clinical research. In the last few years, our group focused its interest on lung cancer, both small cell and non-small cell. The group is composed of experts from various disciplines in oncology. The clinical interest of the group has focused on two aspects of lung cancer: quality of life and treatment of elderly patients. Our group is giving significant contributions to the field of lung cancer. Today, large controlled clinical trials are ongoing.

Aged↗
PubMed2000

Chemotherapy of advanced non small cell lung cancer in the elderly: an update.

In the last years there has been a growing awareness in the oncological community about the size of the problem of cancer in the elderly. More than 30% of lung cancers arise in patients aged 70 years or more. Elderly patients tolerate chemotherapy poorly and are not considered eligible for aggressive cisplatin based chemotherapy in clinical practice. A few papers have been published on chemotherapy of elderly NSCLC patients. Cisplatin based chemotherapy seems to be tolerated poorly. Vinorelbine as a single agent showed active and good tolerance. A phase III randomized trial, named ELVIS (Elderly Lung Cancer Vinorelbine Italian Study), showed a survival and quality of life benefit of vinorelbine versus supportive care. Among the new drugs gemcitabine can be considered more promising. Future trials should attempt to improve the results of vinorelbine chemotherapy and include geriatric and quality of life evaluations.

Aged↗
PubMed2000

A three-week schedule of gemcitabine-cisplatin in advanced non-small-cell lung cancer with two different cisplatin dose levels: a phase II randomized trial.

BACKGROUND: To explore a new schedule of gemcitabine-cisplatin (GP) combination therapy using two different cisplatin doses in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From May to December 1997, 92 chemonaive patients entered the study and 88 (28 with locally advanced and 60 with disseminated NSCLC) were evaluable for response and toxicity (45 in arm A and 43 in arm B). Patients were randomly assigned to arm A or arm B. Gemcitabine 1000 mg/m2 was given on days 1-8 plus cisplatin 100 mg/m2 in arm A and cisplatin 70 mg/m2 in arm B on day 2 of every 21-day cycle. RESULTS: The overall response rates in arms A and B were 42% (95% confidence interval (CI): 27.8%-56.7%) and 47% (95% CI: 31.6%-61.5%), respectively. Median duration of response was 9.7 months (range 1.8 to 30.9 months; 13.1 and 9.5 months for arm A and B, respectively), and median survival was 12 months (range 0.2 to 31.1 months; 15.4 and 11.5 months for arm A and B, respectively). Major WHO grade 3-4 toxicities in arm A vs. arm B included: thrombocytopenia (23% vs. 17% of courses), leukopenia (15%, vs. 4% of courses), anemia (7% vs. 6% of courses), and nausea-vomiting (20% vs. 7% of patients). Grade 1-2 nephrotoxicity occurred in 20% of patients in arm A and in 7% of patients in arm B, with one grade 4 episode in arm A. Six patients discontinued treatment because of toxicities, 5 in arm A and I in arm B. CONCLUSIONS: Results of this trial indicate that both schedules are feasible and active, with a milder toxicity in the arm with the lower cisplatin dose.

Adult↗
PubMed2000

Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators.

Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.

Adult↗