Showing papers by "Flavia Longo published in 2012"

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

Abstract: Summary Background 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. Methods 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. Findings 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 One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy.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 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. Interpretation 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. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tematica de Investigacion Cooperativa en Cancer.

TAILOR: Phase III trial comparing erlotinib with docetaxel in the second-line treatment of NSCLC patients with wild-type (wt) EGFR.

Abstract: LBA7501 Background: While the benefit of EGFR tyrosine kinase inhibitors in the treatment of patients with NSCLC harboring EGFR mutations has been widely established, their value in treating patients with wt EGFR is still debated. To assess the role of erlotinib in these patients, we performed an independent multicenter phase III trial (Tarceva Italian Lung Optimization Trial [TAILOR] NCT00637910), comparing erlotinib to docetaxel in second line treatment, having overall (OS) and progression free survival (PFS) as principal and secondary endpoints, respectively. Methods: EGFR and KRAS mutational status were assessed by direct sequencing in all eligible patients; only patients with wt EGFR NSCLC (exons 19 and 21) at progression, and previously treated with a first line platinum-based regimen, were randomized to receive either erlotinib 150 mg daily or docetaxel 75 mg/m2 (3-weekly) or 35 mg/m2 (weekly) until disease progression or unacceptable toxicity occurred. To detect an hazard ratio of 0.67 (2-sided 5%...

Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer

Abstract: The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.

Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin‐based chemotherapy

Abstract: SUMMARY Introduction: With repeated courses of chemotherapy, chemotherapy-induced nausea and vomiting (CINV) becomes progressively more difficult to control. The aim of this study was to evaluate whether the antiemetic efficacy of the triple combination aprepitant, palonosetron and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ‡ 50 mg ⁄m 2 ). Methods: Chemotherapy-naive patients receiving cisplatin-based HEC, were trea- ted with palonosetron 0.25 mg ⁄i.v., dexamethasone 20 mg ⁄i.v. and aprepitant 125 mg ⁄p.o. 1 h before chemotherapy. Aprepitant 80 mg ⁄p.o. and dexametha- sone 4 mg ⁄p.o. were administered on days 2-3. The primary endpoint was com- plete response (CR, no vomiting and no use of rescue medication), over 5 days following HEC in up to six cycles. Secondary endpoints were emesis-free and nau- sea-free rates. Safety was also evaluated. Results: One hundred and fifty six lung cancer patients were included in the study; the median age was 64 years and 76.9% were men. The minimum cisplatin dosage was 75 mg ⁄m 2 , and in most patients was combined with another drug (87.4%). CR ranged from 74.4% (first cycle) to 82% (sixth cycle). More than 90% and 60% of patients were emesis-free and nausea-free during all chemotherapy cycles. The most commonly reported side effects were constipation and headache. Conclusions: The triple combination of aprepitant, palonosetron and dexamethasone enhanced not only the antiemetic protection during the first cycle, but its efficacy was also sustained for up to six cycles of cisplatin-based HEC in lung cancer patients. What's known It is already known that palonosetron and aprepitant are efficacious to prevent nausea and vomiting induced in patients receiving high emetogenic chemotherapy. The efficacy of a triple combination palonosetron, aprepitant and dexamethasone to prevent CINV has been assessed only during one chemotherapy cycle (the first).

HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma

Abstract: The purpose of the study was to evaluate the expression of the biomarkers CA125 and HE4 combined with imaging, in patients with advanced epithelial ovarian cancer (EOC). Forty-six women with EOC were included in the study all affected with peritoneal carcinomatosis. Twenty-two of 46 patients (group I) had peritoneal carcinomatosis with small implants in single or in multiple sites (score 1); 24/46 patients (group II) had macro-nodular implants and omental thickening (score 2). High levels of CA125 (350 ± 11, mean ± SEM) have been observed in 21/22 patients of group I, and a similar value (370 ± 13) has been observed in all patients belonging to group II. HE4 positivity values (350 ± 9) have been observed in all group I patients, whereas all patients belonging to group II showed a higher value of HE4 (600 ± 12). Statistically significant differences were observed between the HE4 levels observed in group I patients in comparison with group II patients (p < 0.0001). In addition, we expressed the extension of lymph nodal disease in three scores: L1–L2–L3, and a statistically significant correlation was observed between high HE4 levels and severity of lymph nodal disease L3 (p < 0.0001). The availability of biomarkers, particularly HE4, together with sophisticated imaging techniques, strengthens the clinical relevance of this study, for the follow-up of patients with peritoneal carcinomatosis.

Efficacy and tolerability of long-acting octreotide in the treatment of thymic tumors: results of a pilot trial.

Abstract: ObjectivesOctreotide is a somatostatin analog, long-acting formulations of which have been used experimentally for the treatment of patients with invasive tumors and/or residual disease after conventional therapies. The objective of this retrospective study was to evaluate the efficacy of long-actin

Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice.

Abstract: Aim: The effect of KRAS status on response to bevacizumab plus chemotherapy in metastatic colorectal cancer is still unclear. We aimed to evaluate the overall clinical response to such a therapy in clinical practice and assess the role of KRAS status on therapy response. Patients & methods: This was a retrospective study enrolling 108 metastatic colorectal cancer patients. KRAS mutation analysis was performed by PCR. Results: Overall, 41.7% of patients had stable disease, 39.8% a partial response, 3.7% a complete response and 14.8% disease progression. Both clinical benefit and objective response rate tended to be higher in patients with only hepatic metastases than those with extrahepatic or multiple metastases. Response to therapy would appear to be independent of KRAS status, but larger studies are needed. Conclusion: Bevacizumab plus chemotherapy provides clinical benefit and objective response rate in patients with metastatic colorectal cancer independently of KRAS expression, especially in those pat...

Capecitabine in elderly patients with metastatic breast cancer.

Abstract: Aims and background Capecitabine is the reference treatment for anthracycline- and/or taxane-pretreated metastatic breast cancer (MBC). This study examined its efficacy, tolerability and impact on the quality of life of elderly patients with MBC. Materials and methods Between January 2002 and December 2009, 75 consecutive elderly patients with MBC received first-line chemotherapy with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks. Endpoints were efficacy, tolerability and clinical-benefit response measured every 3 cycles. Results Median age was 76 years (range 65-88); median ECOG performance status was 1 (range 0-2); 51 patients (68%) had received adjuvant chemotherapy and all patients had received hormonal therapy. Median exposure was 6 cycles. After 3 cycles, 11 patients (14.7%) had a partial response, one patient experienced a complete response, and 49 patients (65.3%) had stable disease, amounting to a disease control rate of 81.3%. Stable disease was maintained in 45 patients (60%) after 6 cycles, in 21 patients (28%) after 9 cycles, and in 13 patients (17.3%) after 12 cycles. A clinical-benefit response was experienced by 42 patients (56%), indicating a positive impact on quality of life. Treatment was well tolerated, the most common grade 3 events being diarrhea (12%) hand-foot syndrome (8%), and mucositis (8%). Adverse events were managed with dose adjustments and supportive therapy when required. Conclusions Our results indicate that capecitabine is active and well tolerated in elderly patients with MBC. This dosing regimen warrants further study in the first-line setting for patients with less aggressive MBC who are not candidates for combination therapy.

Evaluation of relapse-free survival in T3N0 colon cancer: The role of chemotherapy—A multicentric retrospective analysis.

Abstract: 578 Background: Use of adjuvant chemotherapy (AC) in stage II colon cancer (CC) is still under debate. Choice should be based on patients (pts) and disease characteristics. According to worldwide g...

HE4 and CA72.4 are Useful Biomarkers in the Follow-up of Epithelial Ovarian Cancer

Abstract: The aim of this study was to investigate the role of serum biomarkers HE4 and CA72.4 at diagnosis and in the follow-up of patients with epithelial ovarian cancer (EOC).Seventy-eight patients with EOC were included and 40 of them were monitored during the follow-up. Serum levels of HE4 and CA72.4 were determined for all patients at diagnosis. Among these patients, the number of cases with an elevated level of each individual marker HE4 and CA72.4 was 85% and 72% respectively. A statistically significant difference was observed between the positivity of HE4 in comparison with Ca72.4 (p<0.02). In the follow-up period, we observed that tumor marker levels showed fluctuations during chemotherapy. As we combined the individual biomarkers, we observed increased values in 75% of the patients for HE4 with CA 72.4. In conclusion, our study has shown that the association of the biomarkers HE4 and CA72.4 provides a valuable contribution to the follow-up of EOC.