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Biomedical subjects

C Gridelli

Publications and source records attributed to C Gridelli.

At least 55 records · Page 3Linked to original sources
PubMed2000

Detection of circulating tumor cells in carcinoma patients by a novel epidermal growth factor receptor reverse transcription-PCR assay.

The epidermal growth factor receptor (EGFR) is overexpressed in 50-70% of human primary breast, lung, and colon carcinomas, whereas it is not usually expressed in hematopoietic cells. We developed a novel reverse transcription-PCR (RT-PCR)-Southern blot assay for the detection of circulating, EGFR mRNA-expressing tumor cells in carcinoma patients. The assay was set up by increasing the amount of cDNA step by step in the PCR reaction. The highest sensitivity and specificity were found when using 800 ng of cDNA in the PCR reaction. Peripheral blood samples from 91 patients with either colon (38), lung (30), or breast (23) carcinomas and from 38 healthy volunteers were analyzed. EGFR transcripts were found in 44 of 75 (59%) patients with metastatic carcinoma and in 4 of 38 (10.5%) healthy donors (P < 0.001; chi2 test). The expression of EGFR, cytokeratin 19, and carcinoembryonic antigen mRNA in blood samples from patients with metastatic colon carcinoma was compared. EGFR, cytokeratin 19, and carcinoembryonic antigen transcripts were found in 8 of 11 (73%), 3 of 11 (27%), and 5 of 11 (45%) patients, respectively. Furthermore, two of seven (29%) Dukes' B and five of nine (55%) Dukes' C colon carcinoma patients were found to express EGFR mRNA in the peripheral blood. All patients that expressed EGFR transcripts in the peripheral blood were found to express the EGFR protein in the corresponding primary carcinoma, as assessed by immunohistochemistry. These data suggest that the EGFR assay that we developed is a highly specific and sensitive technique to detect circulating tumor cells in patients affected by different carcinoma types.

Breast Neoplasms↗
PubMed1999

A Phase II study of gemcitabine in patients with malignant pleural mesothelioma. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

BACKGROUND: Gemcitabine has shown activity in patients with less chemosensitive solid tumors. Phase II screening of novel drugs is an accepted method with which to investigate new therapies in malignant mesothelioma. The European Organization for Research and Treatment of Cancer-Lung Cancer Cooperative Group has performed several sequential Phase II trials of new agents for the treatment of mesothelioma over the last 10 years. METHODS: Twenty-seven chemotherapy-naive patients with histologically proven malignant mesothelioma were treated with gemcitabine as a 30-minute intravenous administration of 1250 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Therapy continued for up to ten cycles unless disease progression or excessive toxicity mandated discontinuation. RESULTS: With a median relative dose intensity of 96%, toxicity was mild and neutropenia of > or = Grade 3 (according to National Cancer Institute criteria) occurred in 30% of patients, without episodes of febrile neutropenia. One case of hemolytic-uremic syndrome, most likely related to gemcitabine use, was observed. Overall, 2 objective responses were observed (response rate of 7%; 95% confidence interval, 1-24%). The median survival was 8 months. CONCLUSIONS: At the prescribed dosage and schedule, single agent gemcitabine appears to have limited activity in chemotherapy-naive patients with malignant pleural mesothelioma.

Adult↗
PubMed1999

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.

Adult↗
PubMed1999

Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: A phase II trial.

PURPOSE: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m(2) once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.

Adult↗
PubMed1998

A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum. Italian Co-operative Group on Bladder Cancer.

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.

Adult↗
PubMed1998

Carboplatin plus vinorelbine, a new well-tolerated and active regimen for the treatment of extensive-stage small-cell lung cancer: a phase II study. Gruppo Oncologico Centro-Sud-Isole.

PURPOSE: To evaluate the activity and toxicity of the combination carboplatin plus vinorelbine in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: A two-stage optimal Simon design was applied. To proceed after the first stage, responses from 8 of 11 treated patients were needed. Overall, 31 responses of 43 treated patients were required to comply with the design parameters. Inclusion criteria were cytohistologically proven SCLC; extensive disease; age of 70 years or less; Eastern Cooperative Oncology group performance status (ps ECOG) 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 carboplatin 300 mg/m2 intravenously (i.v.) day 1 and vinorelbine 25 mg/m2 i.v. on days 1 and 8 every 4 weeks up to six cycles. Of 43 enrolled patients, 36 were men and 7 women, with a median age of 63 years (range, 46 to 70 years). RESULTS: All patients were assessable for response and toxicity. We observed 32 (74%) objective responses, with 23% complete responses. Median time to progression was 25 weeks, and median survival was 37 weeks. The treatment was well tolerated. The reported main toxicities were leukopenia grade 3 in 21% of patients and grade 4 in 5% of patients, anemia grade 2 in 11% of patients and grade 3 in 2% of patients, and thrombocytopenia grade 3 in 7% of patients. CONCLUSION: These data show that carboplatin plus vinorelbine is an active and well-tolerated regimen in extensive SCLC. In view of the activity, low toxicity, and ease of administration, it may be a reasonable alternative to more toxic cisplatin-containing regimens.

Aged↗
PubMed1998

Gemcitabine as second-line treatment for relapsing or refractory advanced non-small cell lung cancer: a phase II trial.

We investigated the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. From November 1995 to October 1997, 83 patients (73 men and 10 women) with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m2 on a weekly x 3 every 4 weeks schedule. Responses were assessed every two treatment courses. The median age of the patients was 63 years. Eastern Cooperative Oncology Group performance status was 0-1 in 62 patients; 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and I stage IIIA). Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well-tolerated: leukopenia and thrombocytopenia World Health Organization grade 2-3 occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients and peripheral edema was observed in 5% of patients. Nausea and vomiting were present in 16% of patients. In this study, gemcitabine showed significant activity in a patient population usually associated with poor prognosis. This finding suggests a possible role for gemcitabine as second-line treatment in patients who have recurring disease or who have failed a platinum-containing regimen, and in the absence of significant toxicity.

Adult↗
PubMed1997

Vinorelbine is well tolerated and active in the treatment of elderly patients with advanced non-small cell lung cancer. A two-stage phase II study.

More than 30% of lung cancers arise in patients aged 70 years or more; however, because elderly patients are not considered to tolerate chemotherapy, they are generally excluded from clinical trials and are not considered eligible for aggressive cisplatin-based chemotherapy in clinical practice. The aims of the present study were to test tolerability and activity of weekly vinorelbine in advanced non-small cell lung cancer (NSCLC) patients aged 70 years or more, and to define whether minimum conditions existed for a randomised comparison with best supportive care. The study was designed as a multicentre two-stage phase II trial according to Simon's optimal design: 8 or more responses out of 43 treated patients were expected at the end of the trial. Patients aged 70 years or more were eligible if they had a cytological or histological diagnosis of NSCLC at stage IIIb-IV and a performance status less than or equal to two according to the ECOG scale. Vinorelbine was given intravenously (i.v.) at a dose of 30 mg/m2 every week for 12 doses. As planned, 43 patients entered the study; median age was 73 years (range 70-80); 11 patients were older than 75 years. Median dose-intensity (mg/m2/week) of vinorelbine was 21.2 (range 7.5-30) and was not affected by age of patients. Toxicity was generally mild, mainly haematological and never life-threatening. ECOG performance status improved in 26% of patients; cough and pain improved in more than 40% of patients symptomatic at entry, while dyspnoea improved in 28%; approximately half the patients had a stabilisation of their symptoms. 10 patients (23-95% exact confidence interval (CI): 12-39%) obtained a partial response. Median time to progression was 11 weeks (95% CI 8-30) and median survival 36 weeks (95% CI 28-53). One-year estimated progression-free and overall survival rates are 16% and 36%, respectively. In conclusion, vinorelbine was well tolerated and active in the treatment of elderly NSCLC patients. A phase III trial (ELVIS-Elderly Lung Cancer Vinorelbine Italian Study) comparing best supportive care versus best supportive care plus vinorelbine is now ongoing.

Age Factors↗
PubMed1996

Phase I study of ifosfamide plus high-dose epirubicin in advanced non-small-cell lung cancer.

The present phase I study was designed to determine the maximum tolerated dose (MTD) of epirubicin given in combination with ifosfamide at a dose of 3 g/m2, recycled every 4 weeks, in patients with advanced non-small-cell lung cancer (NSCLC). A total of 18 patients entered the study; they received the following four dose levels of epirubicin (i.v., day 1): 75 (6 patients), 90 (3 patients), 105 (3 patients, and 120 mg/m2 (6 patients). The MTD of epirubicin was 120 mg/m2, neutropenia being the dose-limiting toxicity. We observed 1/6, 1/3 1/3, and 2/6 partial responses (PRs) at epirubicin dose levels of 75, 90, 104, and 120 mg/m2, respectively. A phase II study of epirubicin given at a dose of 120 mg/m2, in association with conventional-dose ifosfamide in advanced NSCLC is in order.

Aged↗
PubMed1996

Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. The "Gruppo Oncologico Centro-Sud-Isole' (G.O.C.S.I.).

PURPOSE: To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. PATIENTS AND METHODS: 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/m2+cisplatin 100 mg/m2 i.v. day 1 and vindesine 3 mg/m2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/ m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1 to 3 with cycles repeated every 3 weeks. For both treatments a maximum of 6 cycles was planned. Response and toxicity were evaluated according to WHO. Subjective responses were assessed by numerical scales. Analyses were made on the basis of intent to treat. RESULTS: The objective response rate was 21.4% (1 CR + 21 PR among 103 patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients) in the MVP arm (P = 0.48). Symptoms were similar in the two arms. 196 patients progressed and 182 died. The median times to progression were 10 weeks (95% CI 9-12) and 12 weeks (95% CI 10-15) and median survivals were 29 weeks (95% CI 25-36) and 28 weeks (95% CI 25-35) in the MEV and MVP arms, respectively. The relative risks of progressing and of dying were 0.89 (95% CL 0.66-1.20) and 0.96 (95% CL 0.71-1.30), respectively, for patients receiving MVP as compared with those receiving MEV at multivariate analysis adjusted by sex, age, histologic type, number of metastatic sites, performance status at entry, and centre. CONCLUSIONS: In the present study, no significant differences were observed in response rate, survival or palliation of symptoms between the MEV and MVP regimens, while toxicity was significantly more frequent and severe with MVP. Thus, MEV should be considered a reasonable alternative to the MVP regimen in the treatment of stage IV NSCLC.

Adult↗
PubMed1996

Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer.

In attempt to develop a new chemotherapeutic regimen including carboplatin (CBDCA), epirubicin (EPI), and VP-16 in extensive small cell lung cancer, with a higher dose intensity compared with previous experience of our group, we determined the maximum tolerated dose (MTD) of VP-16 when administered in association with CBDCA (300 mg/ m2, i.v., day 1) and EPI (75 mg/m2, i.v., day 1), recycling chemotherapy every 3 weeks, with the support of granulocyte-colony-stimulating factor (G-CSF). A total of 15 patients received three dose levels of VP-16 (mg/m2, i.v., daily on days 1-3): 100 (three patients), 120 (six), and 140 (six). G-CSF was administered subcutaneously at the dose of 5 micrograms/kg/day on days 6-15 of each chemotherapy course. The MTD was established at 140 mg/m2 and myelotoxicity, grade 4 neutropenia with death for sepsis in one case and grade 3 thrombocytopenia in three cases, was dose limiting. The recommended dose of VP-16 for a phase II study is 140 mg/m2.

Adult↗
PubMed1994

Mitomycin C etoposide and vinorelbine (MEV II) in the treatment of metastatic stage IV non small cell lung cancer.

AIMS AND BACKGROUND: In a prior study with a new non-cisplatin-based regimen including mytomycin C, etoposide and vindesine (MEV I) we observed a 37% response rate and very low toxicity in stage IV non small cell lung cancer. In an attempt to improve the activity of MEV I we evaluated a new regimen, MEV II, a modification of MEV I in which vinorelbine replaced vindesine. METHODS: 21 patients with metastatic stage IV non small cell lung cancer entered the phase II trial and were treated with the MEV II regimen (mitomycin C 8 mg/m2, i.v., d 1, etoposide 100 mg/m2, i.v., d 1-3, vinorelbine 30 mg/m2, i.v., d 1, every 4 weeks. RESULTS: We observed a partial response rate of 30% (95% confidence limits 10-50) with a median survival of 6 months. The worst reported toxicity was leukopenia grade 4 in 10% of patients including one who died of sepsis and grade 3 in 20%. CONCLUSIONS: The MEV II regimen showed a similar activity but greater toxicity than MEV I.

Aged↗
PubMed1994

Carboplatin plus epirubicin plus VP-16, concurrent 'split course' radiotherapy and adjuvant surgery for limited small cell lung cancer. Gruppo Oncologico Centro-Sud-Isole (GOCSI).

Thirty-three patients with limited small cell lung cancer (SCLC) received carboplatin, epirubicin and VP-16 chemotherapy, concurrent 'split course' thoracic radiotherapy, followed by surgery for patients achieving an objective response (OR). High-risk patients and those staged T4-N3 (IIIB) at diagnosis, were excluded from surgery. After induction chemoradiotherapy we obtained 90.9% OR, with 63.3% obtaining complete response (CR). Ten patients (30.3%) were eligible for surgery after induction therapy. Five patients (15.1%) were subjected to surgery and five additional patients refused. Of the five patients who were subjected to surgery, four had a complete response (CR), (three pathological confirmations), and one had a partial response (PR), (unresectable). The median survival time for all patients was 16 months with 12.1% of the long-term survivors still living after 2 years and 9% still living after 3 and 4 years. Toxicity consisted mainly of myelosuppression. This study shows a high activity of the chemotherapy and the chemoradiotherapeutic regimen employed but a low feasibility for adjuvant surgery in SCLC.

Adult↗
PubMed1994

Carboplatin, epirubicin, and VP-16 chemotherapy in the treatment of small cell lung cancer.

In our study, 72 SCLC patients, 23 with limited and 49 with extensive disease, were treated with carboplatin, epirubicin, and VP-16 (CEV) chemotherapy (CBDCA 300 mg/m2 day 1, EDX 50 mg/m2 day 1, VP-16 100 mg/m2 i.v. days 1-3, every 4 weeks). Patients with limited disease were also subjected to concurrent "split-course" chest radiotherapy followed by surgery in responders if they were not staged IIIB at diagnosis. In limited disease we obtained 96.5% objective responses (OR) with 52.5% complete responses (CR), a median survival of 14 months, with 13% long-term survivors at 30 months. In extensive disease we obtained 83.6% OR with 28.5% CR, and a median survival of 10 months. Toxicity consisted mainly of manageable myelosuppression, especially for limited disease. These data show high activity of CEV chemotherapeutic regimen.

Adult↗
PubMed1994

Mitomycin C and mitoxantrone in anthracycline-pretreated advanced breast cancer patients. A phase II study.

Twenty-one patients with anthracycline-pretreated advanced breast cancer were treated with mitomycin C plus mitoxantrone (MM), 10 mg/m2, on day 1 of a 28-day cycle. All patients were evaluated for toxicity and response. Overall, 83 cycles were administered, with a median number of 4 cycles per patient. Hematologic toxicity, not requiring hospitalization, was the major side effect. Vomiting occurred in 19.2% of cycles. Objective response rate was 33.3% (95% confidence interval: 12.2-53.1%); best responses were 1 complete and 6 partial; also 7 stable and 7 progressive disease were recorded. The best responding site was the viscera, the worst was bone. Responses were seen preferentially in second- rather than in third-line therapy and in patients who had responded to previous chemotherapy, although differences were not statistically significant. Kaplan-Meier estimated median time to progression and overall survival were 26 weeks (range: 2-67 weeks) and 35 weeks (range: 6-79 weeks), respectively. In conclusion the MM regimen showed acceptable toxicity and appreciable activity in anthracycline-pretreated advanced breast cancer.

Adult↗