S. Romito

Phase III Randomized Trial of FOLFIRI Versus FOLFOX4 in the Treatment of Advanced Colorectal Cancer: A Multicenter Study of the Gruppo Oncologico Dell’Italia Meridionale

PURPOSE We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen). RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. CONCLUSION There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Comparison of CHOP-B vs CEOP-B in ‘poor prognosis’ non-Hodgkin’s lymphomas. A randomized trial

Sixty consecutive previously untreated patients with non-Hodgkin’s lymphomas (intermediate or high grade and/or bulky disease and/or presence of constitutional symptoms), were randomized to receive either CHOP-B or CEOP-B (31 and 29 patients, respectively) to compare the therapeutic activity and toxicity.Complete response was observed in 65% of the patients treated with CHOP-B and 62% with CEOP-B; relapse of the disease occurred, respectively, in 5/20 (25%) and 6/18 (33%) of CR. Relapse-free survival and overall survival at 5 yr resulted in both groups (RFS 68% and 62% and overall survival 62% and 62%, respectively).In addition, increasing the dosage of epirubicin did not result in an increase in the haematologic toxicity or percent of CR. The haematologic toxicity was slightly lower in CEOP-B.The cardiologic monitoring (Eco 2D and EKG-Holter) at 400 mg mq−1 of EDX and ADM did not demonstrate variations in cardiac function in the CEOP-B group, while in the ADM patients the ejection fraction was statistically lower as regards basal values.In conclusion, in our randomized study, substitution of ADM with EDX in non-Hodgkin’s lymphomas in the CHOP-B regimen, did not decrease the therapeutic activity of the combined chemotherapy, while less toxicity (haematologic and cardiac) was observed. For these reasons, in our opinion, epirubicin can substitute adriamycin in second and third generation regimens for non-Hodgkin’s lymphomas in which the major drawback for a wider diffusion is the severe toxicity observed.

Gemcitabine and docetaxel every 2 weeks in advanced non-small cell lung cancer: a phase II study of the Gruppo Oncologico Italia Meridionale

INTRODUCTION Platinum-based chemotherapy is the gold standard in advanced non-small cell lung cancer (NSCLC), although with relevant toxic effects. Both docetaxel (DCT) and gemcitabine (GEM) have shown activity as single agent in advanced NSCLC with a different toxicity profile and a lack of cross-resistance. MATERIALS AND METHODS From April 2000 to May 2001, 47 consecutive patients were enrolled in a multicenter phase II trial. Main inclusion criteria included untreated patients with histologically confirmed NSCLC, age</=70 years, stage IIIB/IV, Eastern Cooperative Oncology Group performance status (PS) 0-2, measurable disease, adequate hematologic, cardiac, hepatic and renal functions, and written informed consent. Treatment schedule consisted of DCT at the dosage of 50 mg/m(2) with conventional steroid premedication and GEM at the dosage of 2,000 mg/m(2). Both drugs were administered every 2 weeks without prophylactic use of growth factors. RESULTS Enrolled patients included 40 males and seven females with a median age of 65 years, and a median PS 1. There were 26 squamous carcinomas, 13 adenocarcinomas, and eight others, 13 stage IIIB and 34 stage IV. A total of 371 cycles were administered. Overall 18 partial responses were observed (38.3%); 14 patients were considered as stable disease and 13 showed progressive disease. Two treatment-not related deaths occurred before the first disease evaluation was performed. Median duration of response was 6 months (range 2-10) and median duration of survival was 10.5 months (range 1-25+). One year survival probability was 38% (95% CI 25-54%). In a statistical analysis responses were independent to histology or stage. Grade 3-4 toxicity, according NCI criteria, was mild with neutropenia in eight patients (17%), anemia in two patients (4%). Asthenia affected two patients and mucositis occurred in one patient. CONCLUSIONS In our experience the biweekly combination of DCT and GEM is active and well tolerated and can be administered without G-CSF primary prophylaxis reducing treatment costs. It should be considered as a promising alternative to more toxic platinum-based regimens.

Differences in the availability of new anti-cancer drugs for Italian patients treated in different regions. Results of analysis conducted by the Italian Society of Medical Oncology (AIOM)

Aims and background Italy is divided into 20 regions. As a consequence of local autonomy, following marketing authorization by the Italian Medicines Agency, each drug for hospital use is not immediately available, because its approval needs to undergo further steps that can be different among regions. The Italian Society of Medical Oncology conducted the present study to describe the impact of the existence of sub-national pharmaceutical formularies on the disparity of access to new anti-cancer drugs among patients treated in different Italian regions. Methods The availability of 8 new anti-cancer drugs at a regional level and the coherence of regional authorizations compared with national authorizations approved by the Italian Medicines Agency were analyzed as of April 2009. Results Fifteen regions and autonomous province of Trento have a regional pharmaceutical formulary. In most cases, the regional pharmaceutical formularies include the eight analyzed drugs, with therapeutic indications coherent with national marketing authorization indications. Five drugs (bevacizumab, trastuzumab, rituximab, erlotinib, sunitinib) were included in all the existing regional pharmaceutical formularies, without restrictions, whereas three drugs (cetuximab, sorafenib, pemetrexed) were found to have restrictions in some regions. Conclusions The presence of multiple hierarchical levels of drug evaluation creates a potential element of disparity in the access to pharmacological therapies for Italian citizens. Free full text available at www.tumorionline.it

Abstract P4-13-15: Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real world population of hormone receptor positive advanced breast cancer: A multicenter Italian experience

BACKGROUND: Everolimus, an mTOR inhibitor, in combination with exemestane is approved for hormone receptor (HR) positive advanced breast cancer (ABC), after failure of treatment with non-steroidal aromatase inhibitor (NSAI). We assessed the toxicity of the combination and the correlation between dose intensity and response to therapy, in a real world population of ABC from 11 Italian centers. Moreover, we evaluated OS of the whole population, RR and PFS according to line of treatment (from 1rd to 3th and from 4th on). METHODS: 154 pts were treated with combination of everolimus 10 mg and exemestane 25 mg daily from 05/2011 today. Median age was 62 (47-82). Median time to metastatic disease was 49 months (0-269). Median number of metastatic sites was 2 (55.2% of pts visceral versus 44.8% non visceral disease). N=117 (75.9%) pretreated with HT as adjuvant; N=126 pts (81.8%) treated with HT for advanced disease prior to EVE/EXE, with a median of one line (0-5). N=102 pts (66.2%) treated with chemotherapy for metastatic disease, with a median of one line (0-6) before everolimus treatment. RESULTS: Sixteen pts received EVE/EXE as 1st line (10.4%), 39 as 2nd (25.3%), 37 as 3rd (24%), 62 as 4th or more (40,3%). Response was evaluable in 127 out of 154 pts; CR/PR/SD respectively 5/27/56 pts. RR according to line (from 1st to 3rd vs ≥ 4th) was respectively 22.8% vs 26.4% (p=0,864). The median PFS for all population (150 pts) was 38 weeks (95% CI: 33-42). The PFS according to line (1st- 3rd vs ≥ 4th) was 38 wks in both subgroups, p=0.73. OS (126/154 pts) was 28 mths (95% CI: 31-38). The most frequent adverse events were collected in the table. Median duration of treatment with everolimus 10 mg and 5 mg was respectively 180 (9-854) and 129 days (3-738). Fifty-eight pts (37,6%) never stopped treatment with everolimus 10 mg; 16 pts (10,4%) definitively stopped everolimus for toxicity; 80 pts (52,0%) temporarily interrupted the treatment, resuming at dose level 10 mg (31 pts) or reducing at 5 mg (49 pts). Main reason for discontinuation/interruption was stomatitis G2-G3. RR and PFS evaluated according to dose intensity, 10 mg vs 5 mg, were respectively 25.9% vs 30% p=0.779, 38 wks (27-44) vs 40 wks (31-48) P=0.614 CONCLUSIONS: efficacy in terms of RR and PFS of the combination EVE/EXE is not related to dose intensity (10 mg vs 5 mg), the discontinuation of the treatment is high with the starting dose of 10 mg, the toxicity is consistent with previous phase II-III studies although we collected some different toxicities. Citation Format: Forcignano R, Petrucelli L, Cazzaniga ME, Lupo LI, Chiuri VE, Cairo G, De Matteis E, Febbraro A, Giordano G, Campidoglio S, Fabi A, Giampaglia M, Bilancia D, La Verde N, Maiello E, Morritti M, Giotta F, Lorusso V, Scavelli C, Romito S, Cusmai A, Palmiotti G, Tornesello A, Ciccarese M. Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real world population of hormone receptor positive advanced breast cancer: A multicenter Italian experience. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-15.