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Stefano Margaritora

Publications and source records attributed to Stefano Margaritora.

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

Enduring challenge in the treatment of nonsmall cell lung cancer with clinical stage IIIB: results of a trimodality approach.

BACKGROUND: Stage IIIb (T4/N3) non-small-cell lung cancer (NSCLC) is considered an inoperable disease and treatment is an enduring challenge. Surgery after induction therapy seems to improve locoregional control. We report the results of a phase II prospective trimodality trial (chemotherapy and concomitant radiotherapy plus surgery) in patients with stage IIIb NSCLC. METHODS: From November 1992 to June 2000, 39 patients (37 men and 2 women, mean age 65 years) with clinical stage IIIb (34 T4N0 to 2, 4 T2 to 3N3, 1 T4N3, excluding T4 for malignant pleural effusion) entered the study. They received intravenous infusions of cisplatin 20 mg/m(2) and 5-fluorouracil 1,000 mg/m(2) (days 1 to 4 and 25 to 28) combined with a total dose of 50.4 Gy radiotherapy delivered over 4 weeks (1.8 Gy daily). Upon clinical restaging responders underwent surgery. RESULTS: All patients were available for clinical restaging. No complete response was observed. Twenty-one patients had partial response (53.8%), 16 had stable disease (41%), and 2 had progressive disease (5.2%). Hematologic toxicity was moderate. Twenty-two patients (56.4%), 21 with partial response and 1 with stable disease, underwent surgery with no perioperative death. A radical resection was possible in 21 cases. Nine lobectomies, 3 bilobectomies, and 9 pneumonectomies were performed. Complications occurred in 5 patients (23.6%). Fourteen of the patients who underwent surgery (66.6%) showed a pathologic downstaging. A complete pathologic response was obtained in 9 cases (49%). Overall 5-year survival (Kaplan-Meier) was 23%. Resected versus non-resected patients showed a significant difference: 38% versus 5.6% (p = 0.028, log rank). CONCLUSIONS: This trimodal approach for stage IIIb NSCLC appears safe and effective. It provides good therapeutic results with acceptable morbidity in surgical cases.

Adult↗
PubMed2003

Increasing complexity of farnesyltransferase inhibitors activity: role in chromosome instability.

Oncogenic Ras proteins have been seen as an important target for novel anticancer drugs. Due to the functional role of Ras farnesylation, fanesyltransferase (FTase) inhibition was thought to be a strategy for interfering with Ras-dependent transformation. When farnesylation is blocked, the function of Ras protein is severely impaired because of the inability of the nonfarnesylated protein to anchor to the membrane. Although it has been clearly demonstrated that FTase inhibitors (FTIs) inhibit Ras farnesylation, it is uncertain whether the antiproliferative effects of these compounds result exclusively from the effects on Ras. Moreover, no consensus has been reached as to the relevant targets(s) of FTIs that can explain their mosaic pharmacology. In searching for downstream targets for FTIs effects, CENP-E and CENP-F/mitosin were identified. Different studies showed that the inhibition of farnesylation interferes with CENP-E-microtubule association. In the presence of FTIs, chromosome alignment to the metaphase plate is delayed, suggesting that farnesylated proteins are involved in a step critical to bipolar spindle formation and chromosome alignment. An important question is whether these biological effects might contribute to the chemotherapeutic effects of the FTIs. However, FTIs, triggering the spindle checkpoint, might elevate the rate of cellular missegregation to levels that are incompatible with cell viability, as well as have a reduced (but still significant?) effect on checkpoint-proficient normal cells. As an example, RPR-115135 induced micronuclei (MN) increase in cancer cells displaying high chromosome instability (CIN) levels, whereas in normal cells it is devoid of activity. Cancer cells showing high CIN level might represent an ideal target for the activity of some FTIs.

Alkyl and Aryl Transferases↗
PubMed2002

Phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with inoperable non-small-cell lung cancer.

PURPOSE: To report the evidence of a phase I trial planned to determine the maximum-tolerated dose (MTD) and related toxicity of weekly gemcitabine (GEM) and concurrent radiotherapy in patients with non--small-cell lung cancer (NSCLC). In addition, the response to treatment was evaluated and reported. PATIENTS AND METHODS: Thirty-six patients with histologically confirmed NSCLC deemed unresectable because of advanced stage were observed and treated according to a combined chemoradiation protocol with GEM as chemotherapeutic agent. GEM was given weekly for 5 consecutive weeks as a 30-minute intravenous infusion concurrent with radiotherapy (1.8 Gy/d; total dose, 50.4 Gy). The initial dose was 100 mg/m(2). Pulmonary, esophageal, cardiac, hematologic, and skin toxicities were assessed. The dose of GEM was increased by 50 mg/m(2) up to a dose of 250 mg/m(2); an additional increase by 25 mg/m(2) up to the MTD was planned and realized. Three patients were enrolled for each dose level. RESULTS: Dose-limiting toxicity was identified for the 375-mg/m(2) level with two episodes of grade 2 esophagitis and two of grade 3 pulmonary actinic interstitial disease. The weekly dose of GEM 350 mg/m(2) was well tolerated. CONCLUSION: A weekly GEM dose of 350 mg/m(2) concurrent with radiotherapy was well tolerated. Promising results regarding response to treatment were observed and reported.

Adult↗
PubMed2002

Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial.

BACKGROUND AND PURPOSE: To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated. RESULTS: Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis. CONCLUSIONS: Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable.

Adult↗
PubMed2002

Incidental surgical findings of a phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with unresectable non-small cell lung cancer.

OBJECTIVE: to report the surgical facts of unresectable patients with locally advanced non-small cell lung cancer (NSCLC) treated in a phase I trial with concurrent weekly gemcitabine and radiotherapy who achieved a clinical downstaging so as to re-enter resectability. MATERIALS AND METHODS: from 3/99 to 11/00, 30 patients (ten stage IIIa, 16 IIIb and four IV) with histologically proven, unresectable NSCLC, were enrolled in this phase I trial. Gemcitabine was given weekly for 5 consecutive weeks as a 30-min intravenous infusion, at least 4 h before radiotherapy. Starting dose: 100 mg/m(2). Maximum tolerated dose (MTD): 350 mg/m(2). Radiotherapy total dose: 50.4 Gy (1.8 Gy/day) on primitive tumour and involved lymph nodes. RESULTS: 27 out of 30 patients (90%) were evaluable for clinical restaging (three patients who decided to continue their treatment elsewhere have been excluded). A major clinical response (partial+complete response) was observed in 17 out of 27 cases (62.9%). Clinical complete response rate was 3.7% (1/27) while partial response rate was 59.2% (16/27). Nine patients (33.4%) showed a clinical stable disease and one a disease progression (3.7%). Fourteen patients re-entered resectability and were operated upon: seven lobectomies; four bilobectomies; two pneumonectomies and one explorative thoracotomy. Mean operation duration time was 112 min; mean blood loss was 390 cc. Thirty-day morbidity and mortality were nil. Mean post-operative hospital stay was 6.8 days. A slight increase in operational technical difficulty was encountered. Definitive histology showed a pathologic downstaging of 71.4% (10/14). In four patients, only microscopic neoplastic remnants were found. CONCLUSIONS: combined treatment with weekly gemcitabine and concurrent radiotherapy is feasible. In patients with advanced NSCLC who achieved a good clinical response and therefore were judged to be resectable, surgery was possible without any increase in thirty-day morbidity and mortality. Satisfactory pathologic results were obtained.

Adolescent↗
PubMed2002

Unsuspected primary pulmonary meningioma.

Primary pulmonary meningioma is an uncommon, usually benign, soft tissue tumour which has rarely been reported. We report an additional case of primary pulmonary meningioma occurring in an asymptomatic 56-year-old man whose diagnosis was only established after resection. The features of this lesion together with a review of the previous literature are described.

Humans↗
PubMed2002

Pulmonary metastases: can accurate radiological evaluation avoid thoracotomic approach?

OBJECTIVES: To evaluate the effectiveness of radiological assessment (high-resolution CT (HRCT), helical CT (HCT) scan) of lung metastases and to verify if a complete manual exploration by thoracotomy is necessary. MATERIALS AND METHODS: From 1/96 to 1/00, 166 consecutive patients presenting with lung metastases were treated. Preoperative CT scan (HRCT in 78 patients, group A; HCT in 88 patients, group B) to assess the number, size and location of the lesions (slice thickness 5 mm; reconstruction interval 3-5 mm) was always performed. All patients underwent axillary thoracotomy (staged when lesions were bilateral); accurate palpation of the lung parenchyma was always performed to identify any undetected lesion. Non-metastatic lesions were excluded. RESULTS: We performed 356 wedge resections in 161 patients (113 monolateral, 70.2%; 48 bilateral, 29.8%) and five lobectomies. In group A, primary neoplasm was epithelial in 44 patients, sarcoma in 26 and germ cell in eight, and in group B, epithelial in 61 patients, sarcoma in 20 and germ cell in seven. Three hundred and sixty-one histologically proven metastases were resected (188 in group A and 173 in group B). HRCT correctly identified 142/188 lesions (sensitivity 75%); HCT revealed 142/173 metastases (sensitivity 82.1%). Sensitivity for lesions less than 6 mm in maximum diameter was 48% (30/58 false negative) in group A and 61.5% (20/52 false negative) in group B. CONCLUSIONS: The sensitivity of HCT exceeds that of HRCT. However, complete manual exploration by thoracotomy remains the procedure of choice for patients undergoing pulmonary metastasectomy, because of limitation in preoperative radiological assessment of lung lesions smaller than 6 mm.

Adolescent↗