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L Crinò

Publications and source records attributed to L Crinò.

At least 19 recordsLinked to original sources
PubMed2006

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO).

The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m(2)/daily for 21 days every 28 days until disease progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31-71) with a median KPS of 90 (range 60-100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen.

Adult↗
PubMed2006

A randomized phase II trial evaluating standard (50 mg/min) versus low (10 mg/min) infusion duration of gemcitabine as first-line treatment in advanced non-small-cell lung cancer patients who are not eligible for platinum-based chemotherapy.

PURPOSE: Gemcitabine is one of the most active drugs against non-small-cell lung cancer (NSCLC). Preclinical data suggested that gemcitabine efficacy could be improved by increasing the dose or by increasing the infusion duration. This study has been designed in order to explore two different approaches of gemcitabine dose intensification in patients with advanced NSCLC. PATIENTS AND METHODS: A total of 121 chemonaive patients with locally advanced or metastatic NSCLC not suitable for a platinum-based chemotherapy were randomly allocated to chemotherapy with gemcitabine 1500 mg/m2 on days 1 and 8 every 3 weeks by standard 30 min intravenous infusion (arm A), or gemcitabine 10 mg/m2/min for 150 min on days 1 and 8 every 3 weeks by intravenous infusion at fixed dose rate (arm B). RESULTS: One hundred and seventeen patients were fully analyzed. No difference in response rate (16.1% versus 9.9%, p=0.28), median time to disease progression (4 months versus 4.5 months, p=0.34) median survival (9.8 months in both arms), and 1-year survival (42.6% versus 39.0% p=0.98) was detected in arms A and B, respectively. No treatment-related deaths occurred. Main hematological toxicities were grade 3-4 neutropenia observed in 17.9% of patients in group A and in 49.2% of individuals in group B (p=0.0002). The incidence of febrile neutropenia was 3.3% in arm A and 0% in arm B (p=0.17). Grade 3-4 thrombocytopenia was more frequently observed in arm B patients (9.9% versus 1.8%, p=0.057). Non-hematological toxicity was similar in both arms, and consisted in grade 1-2 gastrointestinal toxicity observed in 48.2% of patients in arm A and 41.0% in arm B. CONCLUSION: Intensification of standard doses or prolonged infusion schedule did not result in efficacy improvement. Gemcitabine infusion duration does not warrant further investigation in patients with advanced NSCLC.

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PubMed2006

Treatment of advanced non-small cell lung cancer.

In the last decade the treatment of advanced-metastatic non-small cell lung cancer has substantially improved. If in the early 90s there was still concern about the real efficacy of chemotherapy over best suppotive care alone in the advanced setting, constant developments in clinical research have demonstrated the survival advantage of active anti-cancer drugs not only in the first-line setting, but, lately, even in patients with recurrent disease after failure of two previous chemotherapy lines. With the premises of high throughput technologies, translational research is aiming to characterize patients and tumors on a molecular basis. With pharmacogenomics it would then be possible to accurately predict patient outcome and tailor the treatment strategy according to the geno-phenotype of single patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Development of gemcitabine in non-small cell lung cancer: the Italian contribution.

Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the most promising new cytotoxic agents. The drug has shown activity in a variety of solid tumors, but appears to be most active in the treatment of non-small cell lung cancer. In this disease, several Italian investigators have evaluated gemcitabine in phase II and III clinical trials. Due to preclinical synergism with cisplatin, the Italian Lung Cancer Project played an important role to assess the efficacy and activity of the gemcitabine-cisplatin combination along with the best doses and schedule to adopt, thus leading to gemcitabine approval for first line treatment of advanced non-small cell lung cancer. Several Italian studies have also investigated gemcitabine non-platinum based combinations, gemcitabine in third generation platinum-based triplets and gemcitabine as second line therapy, but all these studies led to conflicting and inconclusive results. The low toxicity profile makes the drug a valid option for unfit and elderly patients. The Multicenter Italian Lung Cancer in the Elderly Study was a phase III randomized trial conducted in elderly patients with advanced non-small cell lung cancer that showed that single agent gemcitabine is at least as effective as either single agent vinorelbine or the combination of gemcitabine and vinorelbine. In the neoadjuvant treatment of stage III disease, a number of phase II studies with third generation platinum-based doublets or triplets have been conducted by Italian investigators with encouraging results. Current clinical trials are addressing the role of gemcitabine in combination with new targeted therapies. Future studies should be designed in order to identify subgroups of patients who are more likely to benefit from gemcitabine chemotherapy.

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PubMed2005

Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer.

This phase II study evaluated the response rate and tolerability of gemcitabine-oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients. Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m(-2) on days 1 and 8, followed by oxaliplatin 130 mg m(-2) on day 1. Cycles were repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60 patients were enrolled into the study in seven Italian institutions. We observed one complete response (1.7%) and 14 partial responses (23.3%), for an overall response rate of 25.0% (95% confidence interval, 14.7-37.9%). The median duration of response was 5.9 months (range 1.5-17.1 months). With a median follow-up of 6.7 months, median time to progressive disease and overall survival were 2.7 (range 1.9-3.4 months) and 7.3 months (range 7.2-8.6 months), respectively. The main grade 3-4 haematological toxicities were transient neutropenia in 11.7% and thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3-4 nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%) patients developed grade 3 neurotoxicity. Our results show that gemcitabine-oxaliplatin chemotherapy is active and well tolerated in patients with advanced NSCLC, deserving further study, especially for patients not eligible to receive cisplatin.

Adult↗
PubMed2005

Cost-minimisation analysis comparing gemcitabine/cisplatin, paclitaxel/carboplatin and vinorelbine/cisplatin in the treatment of advanced non-small cell lung cancer in Italy.

A retrospective cost-minimisation analysis was conducted comparing novel chemotherapies for the treatment of chemo-naive patients with locally advanced, recurrent, and/or metastatic non-small cell lung cancer (NSCLC). Resource use information was obtained from a Phase III randomised trial investigating the efficacy and toxicity of gemcitabine/cisplatin (Gem/Cis), paclitaxel/carboplatin (Pac/Carbo) and vinorelbine/cisplatin (Vin/Cis) combination regimens in 612 patients with advanced NSCLC. Since there were no statistically significant differences between the three treatments in terms of progression-free or overall survival in this trial, a cost-minimisation analysis was considered to be the appropriate type of economic evaluation. The perspective was that of the national healthcare provider in Italy. Medical resource use was obtained from the clinical trial database, from which mean cost streams were calculated for each treatment group. The mean total treatment costs per patient were 8094 euros, 11,203 euros and 9320 euros for the Gem/Cis, Pac/Carbo and Vin/Cis regimens, respectively. Based on resource consumption in a clinical trial, Gem/Cis had the lowest overall mean costs of the three chemotherapy regimens. Gem/Cis therefore has the potential to save costs in the treatment of advanced NSCLC in Italy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma.

We present the results of a phase II trial of carboplatin and etoposide (CE) combination as first-line chemotherapy in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) after surgery and radiotherapy. We assess the activity and the tolerability of this combination. 30 patients with GBM (25) and AA (5) were treated with VP-16 (etoposide) 120 mg m(-2) and CBCDA (carboplatin) 100 mg m(-2) for 3 days every 4 weeks. Moreover, we performed a retrospective analysis of topoisomerase IIalpha gene status using chromogenic in situ hybridisation. The median age was 54 years (21-73 years); Eastern Cooperative Oncology Group performance score was 0-1 in 25 patients and 2 in five patients. All patients had been previously treated with surgical resection (21 radical resections) followed by radiation therapy (40-60 Gy). We observed six (20%) complete responses, three (10%) partial responses and 12 (40%) stable diseases, with a response rate of 30%. The median time to progression was 4 months, while progression-free survival at 6 months was 33.3%. The median survival time was 10 months. Neutropenia occurred in 9 patients: four patients had grade 4, two patients grade 3 and three patients grade 2. In the conclusion of this clinical trial, the CE combination has shown activity in recurrent GBM and AA, with a good toxicity profile. Alterations in the copy number of topoisomerase IIalpha gene seem to be a rare event and in our series do not influence response to the CE combination.

Adult↗
PubMed2004

Efficacy and tolerability of gefitinib in pretreated elderly patients with advanced non-small-cell lung cancer (NSCLC).

The activity and toxicity profile of gefitinib in non-small cell lung cancer (NSCLC) patients aged 70 years or older has been only partially evaluated. The aim of this study was to evaluate the response rate and safety of gefitinib in elderly NSCLC patients. Elderly NSCLC patients pretreated with chemotherapy and with at least one measurable lesion received gefitinib at the daily dose of 250 mg until disease progression, unacceptable toxicity or refusal. From August 2001 to May 2003, 40 consecutive elderly patients have been enrolled onto the study in three Italian institutions. We observed one complete (2.5%) and one partial response (2.5%), 18 disease stabilisations (NC: 45%) lasting at least 2 months, including six patients (15%) who had disease stabilisation of 6 months or longer, for an overall disease control rate of 50% (95% CI: 34.5-65.5%). The median duration of response was 4.4 months (range 1.7-9.2). The side effects were generally mild and consisted of diarrhoea and skin toxicity. Grade 1-2 diarrhoea occurred in 23.6%, and one patient experienced grade 4 diarrhoea, requiring hospitalisation. Grade 1-2 skin toxicity, including rash, pruritus, dry skin, and acne, occurred in 20 patients (52.6%). Gefitinib is safe and well tolerated in elderly pretreated NSCLC patients. The disease-control rate achieved suggests that this drug could represent a valid option in the management of this unfavourable subgroup of patients.

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PubMed2004

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer.

Synergism between anti-HER2 monoclonal antibody (trastuzumab) and paclitaxel has been shown in vitro and in vivo. In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg(-1) i.v. loading dose followed by 2 mg kg(-1) i.v. week(-1)) and paclitaxel (60-90 mg m(-2) h(-1) i.v. infusion week(-1)). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2-38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR+PR) was 56% (95% CI, 36.5-75.5%). The median duration of response was 10.4 months (range 4.1-24.2+). Median time to progression was 8.6 months (range 2.5-24.2+). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline- and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients.

Adult↗
PubMed2004

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer.

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC.

Adult↗
PubMed2004

Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial.

BACKGROUND: Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLC patients with brain metastases. PATIENTS AND METHODS: From January 2001 to May 2003, 41 consecutive NSCLC patients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial. RESULTS: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinoma patients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively. CONCLUSIONS: Gefitinib can be active on brain disease in NSCLC patients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.

Adult↗
PubMed2003

Gliomatosis cerebri: clinical, neurochemical and neuroradiological response to temozolomide administration.

Gliomatosis cerebri is a rare form of diffusely infiltrating glioma that is typically resistant to conventional chemotherapy and radiation therapy and carries a poor prognosis. Temozolomide has shown antineoplastic activity against malignant gliomas and more recently was beneficial in one patient with gliomatosis cerebri. To make an objective assessment of the effect of long-term temozolomide administration in a patient with gliomatosis cerebri we used brain proton magnetic resonance spectroscopy and structural MRI. A 46-year-old man with gliomatosis cerebri was treated with temozolomide (200 mg/m(2) per day for 5 days every 28 days). Twenty cycles of temozolomide resulted in a marked reduction in choline and scyllo-inositol content, as detected using brain proton MR spectroscopy, indicating reduced tumor cellularity and/or growth rate. Neurochemical improvements were associated with normalization of the signal intensity in most of the previously affected cerebral regions and regression of mass effect on MRI. A left pyramidal syndrome, present at the start of the treatment, disappeared. Our observation lends support to larger clinical trials evaluating the use of temozolomide to treat this brain tumor.

Antineoplastic Agents, Alkylating↗
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

New cytotoxics.

Explore the source record for details and available documents.

Antineoplastic Agents↗
PubMed2001

Induction chemotherapy with gemcitabine and cisplatin in stage III non-small cell lung cancer.

The necessity of improving the long-term survival of patients with locally advanced non-small cell lung cancer (NSCLC) points out on the one hand the limit of surgery alone and, on the other hand, the need of combined modality therapy, in which the role of chemotherapy to control distant metastases is prominent. Recent experiences support the efficacy of neoadjuvant chemotherapy with or without radiotherapy. Phase II studies show response rates of 50-80% and median survival longer than 2 years. Phase III studies suggest that neoadjuvant chemotherapy improves survival and objective responses, and induces higher percentages of complete resections compared with surgery alone or chemotherapy and radiotherapy. The gemcitabine-cisplatin regimen has proved its efficacy in NSCLC advanced disease with response rate greater than 40% in phase II and III trials. Representing one of the regimens most used in Europe, its activity has been investigated also in the neoadjuvant setting. Phase II studies have reported an average response rate greater than 60%, complete surgical resections in 60-70% of the cases, and 1-year survival of about 60%. A modern tendency is to use neoadjuvant chemotherapy in very early stages of NSCLC. Gemcitabine-cisplatin regimen has been used as a randomised clinical trial (chemotherapy for early stages trial, CHEST) to compare the efficacy of surgery alone versus surgery plus preoperative chemotherapy in early-stage disease (T2-3N0, T1-2N1, T3N1), and to evaluate the progression free survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Gemcitabine in advanced pancreatic cancer: a phase II trial.

The 5-year survival for pancreatic cancer is usually less than 5%, and no treatment has demonstrated consistent effect on patient survival and disease-related symptoms. Early studies with gemcitabine suggested a modest antitumor activity with significant improvement in disease-related symptoms. This phase II study reports the activity of gemcitabine on 33 consecutive patients with unresectable pancreatic carcinoma. Twenty-three patients had metastatic and 10 locally advanced unresectable disease. Twenty-six patients had not received any previous treatment and seven had received first-line chemotherapy with 5-fluorouracil. Gemcitabine 1,000 mg/m2 was administered intravenously in 30 minutes in the first cycle once weekly for up to 7 weeks followed by 1 week rest; then in subsequent cycles, once weekly for 3 of every 4-week cycle. Four patients obtained partial response (12%). Fifteen patients (45%) had stable disease with a median duration of 32 weeks (range: 16-75 weeks), and 14 patients experienced progressive disease. Median duration of response was 34.5 weeks (range: 19-50 weeks). Median survival was 33 weeks (range: 2-91 weeks). All 4 responding patients and 14 of 15 (93%) patients with stable disease had improvement in performance status and decrease in daily analgesic requirement. Toxicity was mild and mainly consisted of moderate and rapidly reversible myelosuppression. We conclude that gemcitabine chemotherapy was very well tolerated and determined a significant clinical improvement with modest antitumoral activity in patients with advanced pancreatic cancer.

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