Alfonso Illiano

University of Naples Federico II, Napoli, Campania, Italy

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Publications (19)161.24 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are reliably detected by referral laboratories, even if most lung cancer cytology specimens sent to such laboratories contain very few cells. However, EGFR mutations may be distributed heterogeneously within tumors, thereby raising concerns that mutations detected on cytology are not representative of the entire tumor and, thus, are less reliable in predicting response to tyrosine kinase inhibitor (TKI) treatment than mutations detected on histology. To address this issue, the authors reviewed their clinical practice archives and compared the outcome of TKI treatment among patients who were selected by cytology versus patients who were selected by histology. METHODS: From July 2010 to July 2012, 364 cytology samples and 318 histology samples were received. Exon 19 deletions and the L858R point mutation in exon 21, detected by fragment assay and TaqMan assay, respectively, were confirmed by direct sequencing; discrepancies were resolved by cloning polymerase chain reaction products. The response rate (RR) and progression-free survival (PFS) at 12 months (range, 3-34 months) were evaluable in 13 EGFR-mutated patients who were selected for treatment by cytology and 13 patients who were selected by histology. RESULTS: The mutation rate was similar in histology samples (8.5%) and cytology samples (8.8%). The RR (54%) and PFS (9.2 months) were similar in histologically selected patients and cytologically selected patients (RR, 62%; PFS, 8.6 months; P = .88). The disease control rate (responsive plus stable disease) was 92% in histologically selected patients and 100% in cytologically selected patients. CONCLUSIONS: EGFR mutations detected on cytology specimens by a centralized laboratory can predict TKI treatment response equally well as mutations identified on histology samples. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
    Cancer Cytopathology 06/2013; · 4.43 Impact Factor
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    ABSTRACT: Currently, there is a trend towards an increasing use of liquid-based cytology (LBC) to diagnose non-small cell lung cancer. In this study, to detect epidermal growth factor receptor mutations, different molecular techniques were applied to LBC samples with and without laser capture microdissection (LCM). In 58 LBCs, DNA was extracted twice. One sample was obtained directly from CytoLyt solution, whereas the other DNA sample was derived after slide preparation and LCM of Papanicolaou-stained cells. The rate of mutant cases obtained by direct sequencing was discordant between CytoLyt-derived (10.3%) and LCM-derived (17.2%) DNA. However, the same mutant rate (17.2%) was achieved on the matched samples by high-resolution melting analysis, fragment and TaqMan assays. Thus, LCM and direct sequencing may be replaced by more sensitive non-sequencing methods directly performed on CytoLyt-derived DNA, an easier and faster approach to improve epidermal growth factor receptor testing standardisation on LBCs.
    Journal of clinical pathology 04/2012; 65(6):561-4. · 2.43 Impact Factor
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    ABSTRACT: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (> 18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m(2) or AUC 5 with gemcitabine 1000 mg/m(2)) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥ 1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5-5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25-0·54; p < 0·0001). Main grade 3 or 4 toxicities were rash (11 [13%] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.
    The Lancet Oncology 03/2012; 13(3):239-46. · 25.12 Impact Factor
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    ABSTRACT: Socioeconomic status can potentially affect prognosis of cancer patients. Our aim was to describe potential differences in demographic and clinical characteristics, treatment, and survival by education level in patients with advanced non-small cell lung cancer (NSCLC) enrolled in clinical trials of first-line treatment. Individual data of Italian patients with advanced NSCLC (stage IV, or IIIB with supraclavicular nodes or malignant pleural effusion), ECOG performance status (PS) 0-2, enrolled in four phase III randomized trials conducted between 1996 and 2005 were pooled. Information about education was available for 1680 of 1709 patients (98.3%). Patients were divided in two groups according to education level: high (patients with at least high school diploma) or low (those with less than high school diploma). Survival analyses were stratified by treatment arm within trial. There were 312 (19%) and 1368 (81%) patients with high and low education, respectively. Education level was significantly different among birth cohorts, with a time-trend toward higher education level. Patients with high education were significantly younger (median age 65 vs. 70), were less frequently unfit at diagnosis (ECOG PS2 5% vs. 16%), and their tumor type was more frequently adenocarcinoma (47% vs. 37%). Number of treatment cycles received was not significantly different between education groups. Median survival was 9.4 and 7.6 months in high and low education, respectively (p=0.012). At multivariable analysis, female sex, better PS and high education level (Hazard Ratio 0.85, 95%CI 0.73-0.99, p=0.03) were independently associated with longer survival. In Italian patients enrolled in four randomized trials of first-line chemotherapy for advanced NSCLC, high education was significantly more frequent among younger patients, and was associated with lower proportion of PS2 patients. Education level did not significantly affect number of chemotherapy cycles received. Overall survival was longer in patients with high education, after adjustment for PS and other prognostic factors. The exact underlying mechanisms of the independent prognostic role of education level are substantially unknown, but lead-time bias (anticipation in diagnosis and time to inclusion in the trial), differences in adherence to care outside the trial procedures, differences in comorbidities and life-style factors may all contribute.
    Lung cancer (Amsterdam, Netherlands) 01/2012; 76(3):457-64. · 3.14 Impact Factor
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    ABSTRACT: In advanced non-small-cell lung carcinomas epidermal growth factor receptor (EGFR) and KRAS testing is often performed on cytology. Liquid-based cytology (LBC), which eliminates the need for slide preparation by clinicians, may be very useful. In 42 LBC DNA was extracted twice. One sample was obtained directly from CytoLyt solution, whereas the other DNA sample was derived after smear preparation and laser capture microdissection (LCM) of Papanicolaou-stained cells. EGFR and KRAS mutational analyses were performed by direct sequencing. On CytoLyt-derived DNA four EGFR (9%) and five KRAS (12%) gene mutations were found. When direct sequencing was performed after LCM, the rate of cases that displayed either EGFR or KRAS mutations increased from 21% to 40%. Although time-consuming, LCM makes direct sequencing highly sensitive even on LBC preparations containing only a few cells.
    Journal of clinical pathology 09/2011; 65(1):87-91. · 2.43 Impact Factor
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    ABSTRACT: The epidermal growth factor receptor (EGFR) is expressed in the majority of non-small-cell lung cancer (NSCLC). However, only a restricted subgroup of NSCLC patients respond to treatment with the EGFR tyrosine kinase inhibitor (EGFR TKI) gefitinib. Clinical trials have demonstrated that patients carrying activating mutations of the EGFR significantly benefit from treatment with gefitinib. In particular, mutations of the EGFR TK domain have been shown to increase the sensitivity of the EGFR to exogenous growth factors and, at the same time, to EGFR TKIs such as gefitinib. EGFR mutations are more frequent in patients with particular clinical and pathological features such as female sex, nonsmoker status, adenocarcinoma histology, and East Asian ethnicity. A close correlation was found between EGFR mutations and response to gefitinib in NSCLC patients. More importantly, randomized Phase III studies have shown the superiority of gefitinib compared with chemotherapy in EGFR mutant patients in the first-line setting. In addition, gefitinib showed a good toxicity profile with an incidence of adverse events that was significantly lower compared with chemotherapy. Therefore, gefitinib is a major breakthrough for the management of EGFR mutant NSCLC patients and represents the first step toward personalized treatment of NSCLC.
    Pharmacogenomics and Personalized Medicine 01/2011; 4:1-9.
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    ABSTRACT: Two phase I/II trials were done to evaluate the feasibility of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced non-small-cell lung cancer (NSCLC). Patients with advanced NSCLC who were older than 70 years of age and who had a performance status of 0 to 1 were eligible. Cisplatin was given on day 1 (a starting dose of 50 mg/m2 with increasing increments of 10 mg/m2 at each level) and gemcitabine (1,000 mg/m2) or vinorelbine (25 mg/m2) on days 1 and 8. Cycles were repeated every 21 days. A two-stage flexible optimal design was applied in the phase II study, and unacceptable toxicity was the primary end point. Overall, 159 patients were enrolled: 38 in phase I and 121 in phase II studies. Cisplatin was feasible at 60 mg/m2 with gemcitabine and at 40 mg/m2 with vinorelbine. With the former combination, 50 of 60 (83.3%) patients were treated without unacceptable toxicity; objective responses were reported in 26 of 60 patients (43.5%; 95% CI, 30.6 to 56.8); median progression-free and overall survivals were 25.3 and 43.6 weeks, respectively. With the latter combination, 50 (82.0%) of 61 patients were treated without unacceptable toxicity; objective responses were reported in 22 of 61 patients (36.1%; 95% CI, 24.2 to 49.4); median progression-free and overall survivals were 21.1 and 33.1 weeks, respectively. Both cisplatin (60 mg/m2) plus gemcitabine and cisplatin (40 mg/m2) plus vinorelbine are feasible and active in the treatment of elderly patients with advanced NSCLC. The former combination, which provides a higher dose of cisplatin, deserves comparison versus single-agent chemotherapy in this setting of patients.
    Journal of Clinical Oncology 11/2007; 25(29):4663-9. · 18.04 Impact Factor
  • Journal of Clinical Oncology - J CLIN ONCOL. 01/2007; 25(29):4663-4669.
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    ABSTRACT: Platinum-based chemotherapy currently represents standard treatment for advanced non-small cell lung cancer (NSCLC). Gemcitabine is one of the most promising agents currently in use in advanced NSCLC. As a single-agent, epirubicin, showed tumour response rates ranging from 17% to 36% in NSCLC. The aim of the present study was to evaluate the combination of gemcitabine and epirubicin in a phase I-II study. Thirty chemotherapy-naive patients with stage III B-IV NSCLC received gemcitabine at a fixed dose of 1000 mg/m2 on days 1 and 8 every 3 weeks; epirubicin was administered every 21 days on day 1 at the initial dose of 80 mg/m2 which was subsequently escalated. Neutropenia was dose-limiting toxicity since it occurred in 3 out of five patients receiving epirubicin at the dose of 110 mg/m2. An objective response was observed in 14/30 patients, including 2 (7%) complete responses and 12 (40%) partial responses. Median duration of response was 12 months (range: 3 to 53 + months). Median overall survival was 16 months (range: 4 to 55 + months). The combination of gemcitabine and epirubicin is well tolerated. While the observed activity of this combinated treatment matches that of platinum-based regimens, the duration of response and survival have been sufficiently promising to initiate a phase II trial which is currently under way.
    Frontiers in Bioscience 02/2006; 11:2349-53. · 3.29 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Journal of Clinical Oncology 11/2005; 23(28):6865-72. · 18.04 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    The Lancet Oncology 10/2005; 6(9):669-77. · 25.12 Impact Factor
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    ABSTRACT: Docetaxel (75 mg m(-2) 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m(-2) for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, < or =75 years, ECOG PS < or =2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77-1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3-4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.
    British Journal of Cancer 12/2004; 91(12):1996-2004. · 5.08 Impact Factor
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    ABSTRACT: The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.
    British Journal of Cancer 10/2003; 89(6):1013-21. · 5.08 Impact Factor
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    ABSTRACT: The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.Keywords: supportive care, lung cancer, polypharmacotherapy, concomitant drugs
    British Journal of Cancer 09/2003; 89(6):1013-1021. · 5.08 Impact Factor
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    ABSTRACT: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.
    Journal of Clinical Oncology 09/2003; 21(16):3025-34. · 18.04 Impact Factor
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    ABSTRACT: Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I-II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m2; the paclitaxel dose level just below (210 mg/m2) was selected for phase Il evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23-57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8-108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.
    Lung Cancer 01/2001; 30(3):203-10. · 3.39 Impact Factor
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    ABSTRACT: New triplet chemotherapy combinations are under investigation in advanced non small cell lung cancer (NSCLC). Carboplatin, plus paclitaxel, plus gemcitabine is among the most active and promising regimens. The use of more aggressive chemotherapy in order to improve results can increase toxicity. Amifostine (WR-2721) reduces toxicity of radiotherapy and chemotherapy and protects selectively a number of normal, but not neoplastic, tissue. Based on this background, we performed a phase II study on carboplatin, plus paclitaxel, plus gemcitabine with amifostine support in advanced NSCLC. Patients received chemotherapy at the following dosage: carboplatin AUC 5, i.v., at day 1; paclitaxel 175 mg/m2, i.v. by 3-hour infusion, at day 1; gemcitabine 1000 mg/m2, i.v. by 3-hour infusion, at days 1 and 8; every 3 weeks for a maximum of 6 cycles. Amifostine was administered at the dose of 740 mg/m2, i.v., at day 1 of each cycle. Seventeen patients entered the study. They were prevalently male, median age was 62 years, PS (ECOG) was 0 in 10 cases (58.8%), 1 in 6 (35.3%) and 2 in 1 (5.9%). Histology was epidermoid in 8 cases (47%) and adenocarcinoma in 9 (53%). We observed 8 (47.5%) objective responses with 2 (11.7%) complete responses. Median time to progression and median survival were 24 and 36 weeks, respectively. Treatment was well tolerated. The main toxicity was as follows: grade 3 neutropenia, grade 2 thrombocytopenia and grade 3 anemia in one (5.8%) case; grade 2 peripheral neurologic toxicity in 3 (17.6%) patients; grade 2 cardiac toxicity (atrial fibrillation) in one case; and grade 3 respiratory toxicity (dispnoea) in one patient. These data indicate that this combination has promising activity and tolerability. A randomized trial comparing carboplatin plus paclitaxel, plus gemcitabine versus carboplatin, plus paclitaxel, plus gemcitabine, plus amifostine in advanced NSCLC is warranted.
    Anticancer research 01/2000; 20(5C):3999-4003. · 1.71 Impact Factor
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    ABSTRACT: Platinum-based chemotherapy currently represents standard treatment for advanced non-small-cell lung cancer. Gemcitabine is one of the most interesting agents currently in use in advanced non-small-cell lung cancer, and high response rates have been reported when it is administered in combination with cisplatin. The aim of the present study was to evaluate the combination of gemcitabine and carboplatin in a phase I-II study. Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer received carboplatin at area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step. Gemcitabine was administered on days 1 and 8 and carboplatin on day 8 of the 28-day cycle. Dose escalation proceeded up to dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia or grade 3 nonhematologic toxicity. Neutropenia was DLT, inasmuch as it occurred in three of five patients receiving gemcitabine 1,200 mg/m2. Nonhematologic toxicities were mild. Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II studies. An objective response was observed in 13 (50%) of 26 patients, including four complete responses (15%) and nine partial responses (35%). Median duration of response was 13 months (range, 3 to 23 months). Median overall survival was 16 months (range, 3 to 26 months). The combination of gemcitabine and carboplatin is well tolerated and active. Neutropenia was DLT. The observed activity matches that observable in cisplatin-gemcitabine studies, whereas duration of response and survival are even higher. A phase II trial is under way.
    Journal of Clinical Oncology 04/1999; 17(3):921-6. · 18.04 Impact Factor
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    ABSTRACT: Background: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs. Patients and methods: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which vinorelbine was given at a fixed dose of 30 mg/m2 by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial dose of 90 mg/m2, which was subsequently escalated by 30-mg/m2 steps. Cycles were repeated every 21 days. Results: Grade 3 neutropenia was observed only in three patients treated at the fifty dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in three of five patients treated at the fifth dose level (paclitaxel 210 mg/m2). Other side effects were generally mild. The overall response rate in 22 evaluable patients was 32% (95% CI 13–51%); in particular, 1 complete response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended for phase II studies are 180 mg/m2 for paclitaxel and 30 mg/m2 for vinorelbine. The observed myelosuppression was less severe than anticipated on the basis of the effects of each drug alone. Conclusions: The promising activity of this drug combination warrants a phase II study in untreated patients with extensive-stage small-cell lung cancer.
    Cancer Chemotherapy and Pharmacology 10/1997; 41(1):86-90. · 2.80 Impact Factor

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773 Citations
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Institutions

  • 2011–2013
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
  • 2005–2011
    • Monaldi Hospital
      Napoli, Campania, Italy
  • 2003–2005
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 1999
    • Università degli studi di Cagliari
      Cagliari, Sardinia, Italy