Athanasios Athanasiadis

Combination Regimen with Carboplatin, Epirubicin and Etoposide in Metastatic Carcinomas of Unknown Primary Site: A Hellenic Co-Operative Oncology Group Phase II Study

The encouraging results that have been reported for cisplatin combination chemotherapy in a minority of patients with cancer of unknown primary (CUP) together with the previously shown equal activity of carboplatin in this setting, prompted us to investigate the effectiveness of a carboplatin-containing regimen in a phase II clinical trial.Sixty-two evaluable CUP patients entered the protocol. The chemotherapy regimen consisted of carboplatin 300 mg/m2 IV D1, epirubicin 45 mg/m2 IV D1 and etoposide 120 mg/m2 IV D1–3 (CEE regimen) administered every 3 weeks. The median age of the patients was 61 years and 36 were male. Thirty-one diagnosed as poorly differentiated carcinomas (pdc) and the rest as adenocarcinomas. By clinicopathological criteria, 14 patients had a predominately nodal disease with pdc or poorly differentiated adenocarcinomas (pda), 3 women peritoneal carcinomatosis, and the remaining 46 patients had a predominately splanchnic involvement (24 pdc, 22 pda). Twenty-three patients responded to chemotherapy with 4 (6.5%) complete and 19 (30.5%) partial responders (RR 37%, 95% CI 25–49%). An equal activity of the regimen was observed between the two major histopathological types, the pdc and the adenocarcinomas. Nevertheless, significant differences were seen when the CEE regimen was assessed for its activity in the distinct clinicopathological subsets of CUP. Patients with predominately nodal disease of midline distribution with pdc or pda, and women with peritoneal carcinomatosis, achieved a response rate of 64 and 62% respectively, as compared with a 26% response rate for those with predominately splanchnic involvement. Overall median survival was 10 months and for patients with midline distribution 15 months. The regimen was well tolerated. It is concluded that CEE is a relatively nontoxic chemotherapy regimen and easily administered on an outpatient basis. This prospective phase II study confirmed the activity of carboplatin in the chemosensitive subsets of the predominately nodal disease of midline distribution and peritoneal carcinomatosis in women in the CUP syndrome.

A Multicenter Phase II Study of the Combination of Irinotecan and Gemcitabine in Previously Treated Patients with Small-Cell Lung Cancer

Objective: To evaluate efficacy and toxicity of the combination of irinotecan and gemcitabine in pretreated patients having small-cell lung cancer. Patients andMethods: Thirty-one patients (median age 60 years, performance status 0–1 in 87% and 2 in 13% of the patients) with limited or extensive-stage disease, refractory or relapsing after at least one prior chemotherapy regimen, received gemcitabine 1,000 mg/m2 on days 1 and 8 and irinotecan 300 mg/m2 on day 8, every 21 days. Sixteen (52%) patients had sensitive and 15 (48%) refractory disease. Fifteen patients (48%) had received ≧2 prior regimens. Results: All patients were evaluable for toxicity and 26 for response analysis. A median of three (range 1–6) cycles per patient was administered. Three partial responses were documented for an overall response rate of 10% (95% CI 0.73–20.09), and disease stabilization was obtained in 7 patients (22%; intention-to-treat analysis). Two of the responders had refractory, and 1 had sensitive disease. The median time to progression was 4.5 months, the median duration of responses was 2.5 months, and the median survival time was 6 months. Grade 3–4 (WHO) neutropenia was observed in 9 patients (29%), grade 3–4 thrombocytopenia in 4 (13%), and grade 3–4 diahrrea in 3 patients (10%). Three patients experienced febrile neutropenia. No toxic deaths occurred. Conclusions: The combination showed modest activity in this patient group with a poor prognosis. Thus we believe it merits further investigation in the treatment of patients with small-cell lung cancer who have failed one prior chemotherapy regimen.

A phase I-II trial of gefitinib in combination with vinorelbine and oxaliplatin as salvage therapy in women with advanced ovarian cancer (AOC)

5020 Background: To evaluate activity and tolerability of gefitinib (Iressa) in combination with vinorelbine and oxaliplatin as salvage therapy in women with AOC. METHODS Women with AOC recurrent or refractory after ≥ 1 previous line of platinum-containing chemotherapy who had measurable disease by RECIST criteria or assessable by Ca-125 received oral gefitinib 250 mg/day with vinorelbine 25 mg/m2 and oxaliplatin 50 mg/m2 on days 1 and 8 every 3 weeks without prophylactic growth factor support. Gefitinib was continued until disease progression. RESULTS So far 33 patients (pts) have been entered, (10 CDDP-sensitive; 23 CDDP-refractory disease). Among the first 10 pts, 4 DLTs were observed in the first cycle (2 febrile neutropenias, 1 grade 4 neutropenia lasting >5 days, 1 grade 3 diarrhea) resulting in dose reduction for vinorelbine (20 mg/m2) and oxaliplatin (40 mg/m2). In the next 10 pts only 2 DLTs (febrile neutropenia and grade 4 neutropenia lasting >5 days) were observed and the study is ongoing as phase II. All pts were evaluable for toxicity and 29 (19 CDDP-refractory; 10 CDDP-sensitive) for response (2 too early, 1 protocol violation, 1 lost to follow up). Three complete (CR) and 2 partial responses (PR) were seen in the CDDP-refractory group (ORR 23.8%; 95%CI: 5.6-42.0%) and 4 CR with 5 PR in the CDDP-sensitive group (ORR 90%; 95%CI: 71.4-100%). Median duration of response was 5.2 months (range 1-6) for CDDP-refractory and 6.6 (range 1-10) for CDDP-sensitive; median time to progression was 4.1 months (range 1-14) and 8.6 (range 1-12), respectively. So far 8 pts have died (7 disease progression; 1 pulmonary embolism), 14 had disease progression, and 11 continue treatment. 134 cycles have been administered: median 3 (range 1-9) cycles per pt. Τoxicity included grade 3/4 neutropenia each in 8 (24%) pts, febrile neutropenia 4 (12%), grade 3 anemia 1 (3%), grade 3 diarrhea 3 (9%), neurotoxicity 1 (3%), rash 1 (3%) and transaminase elevation 1 (3%). CONCLUSIONS The concurrent administration of gefitinib with vinorelbine and oxaliplatin is feasible and shows promising activity in pretreated pts with AOC. No significant financial relationships to disclose.

Myelotoxicity of oral topotecan in relation to treatment duration and dosage: a phase I study.

Oral topotecan has been recently brought into clinical practice at a dose of 2.3 mg/m2 for 5 days, every 3 weeks. Published data show quite high myelotoxicity. The aim of this trial was to define the daily dose and treatment duration, which permits safe toxicity. The study was designed to begin at a low daily dosage of 1.5 mg/m2 and was escalated by increasing the topotecan dose and the day-treatment duration. The plan was to end up with 2.3 mg/m2 daily for 5 days. In cases of tolerability with the last dosage given, we would then continue testing a higher daily dosage. Treatment repetition was planned to be every 21 days. Dosage levels were 1.5, 2.0 and 2.3 mg/m2 for 3 days, 2.0 and 2.3 mg/m2 for 4 days, and 2.3 mg/m2 for 5 days. Toxicity was scored according to the Common Toxicity Criteria. Thirty-two patients (27 male, five female, median age 60 years, range 46–77 years) with small-cell lung cancer were included. The patients on 1.5 and 2 mg/m2 for 3 days showed no myelotoxicity. Four (25%) patients on 2.3 mg/m2 3-day treatment developed grade 3–4 neutropenia. Three of five patients (60%) treated for 4 days at a dose of 2.3 mg/m2 developed grade 3–4 neutropenia and less than half (two of five, 40%) of these patients had thrombocytopenia. Eight patients (66.7%) on the 5-day treatment presented with serious grade 3–4 myelotoxicity. Two treatment-related deaths were observed in the 5-day group and one in the 4-day group. Granulocyte growth factor was applied in over 60% of the patients. In conclusion, a dose of 2.3 mg/m2 for 5 days was intolerable. Dose-limiting toxicity was 2.3 mg/m2 for 4 days without prophylactic granulocyte colony-stimulating factor administration. The safe duration of oral topotecan treatment and the maximum tolerated dose seem to be not longer than 3 days at a dose of 2.3 mg/m2.

Dose-dense FEC followed by Docetaxel versus Docetaxel plus Cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: A multicenter randomized study by the Hellenic Oncology Research Group (HORG)

BACKGROUND Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide. PATIENTS AND METHODS In this randomized, non-inferiority, phase III trial, women with HER2-negative invasive breast cancer and at least one positive axillary lymph node were randomized to receive either epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and cyclophosphamide (500 mg/m(2)) every 2 weeks for four cycles, followed by four cycles of docetaxel (75 mg/m(2)) every 2 weeks with prophylactic G-CSF support (FEC → D) or docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 21 days for six cycles (TC). The primary end point of the study was the 3-year disease-free survival (DFS) rate. RESULTS Six hundred and fifty women were randomized to either FEC → D (n = 326) or TC (n = 324). After a median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for the FEC → D and TC arm, respectively (hazard ratio = 1.147, 95% confidence interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm (32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low (<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more common with FEC → D. Acute cardiotoxicity was rare (1 event in each group). There were no toxic deaths. CONCLUSIONS This trial did not clearly demonstrate that TC is non-inferior to dose-dense FEC → D. However, 3-year DFS rates were excellent in both arms for women with node-positive, HER2-negative early breast cancer. CLINICALTRIALSGOV NCT01985724.

Modified CAPOX (Capecitabine plus Oxaliplatin) Regimen Every Two Weeks as Second-Line Treatment in Patients with Advanced Colorectal Cancer Previously Treated with Irinotecan-Based Frontline Therapy

Background: To evaluate the efficacy and tolerance of capecitabine (CAP) given every other week and biweekly oxaliplatin (OX; modified CAPOX regimen) in patients with advanced colorectal cancer previously treated with irinote- can-based frontline chemotherapy. Methods: Sixty-seven patients were enrolled; the median age was 62 years and 62 (92.5%) had a performance status (ECOG) of 0–1. OX and CAP were administered at the dose of 100 mg/m2 on day 1 and 2,000 mg/m2 on days 1–7, respectively, every 2 weeks. Results: A total of 429 treatment cycles were administered. Grade 3/4 neutropenia and thrombocytopenia were observed in 4 (6%) and 2 (3%) patients, respectively. Febrile neutropenia complicated 1 treatment cycle. The main nonhematologic toxicities were grade 2/3 peripheral sensory neurotoxicity (10% of patients) and grade 3/4 diarrhea (7%). In an intention-to-treat analysis, 3 (4.5%) complete and 13 (19.4%) partial responses (overall response rate 24%) were observed. Seventeen (24.5%) patients had stable and 27 (40.3%) progressive disease. The median time to tumor progression and overall survival were 5 months and 11.3 months, respectively. Conclusions: The results indicate that the modified CAPOX regimen is safe and effective as salvage treatment in patients with advanced colorectal cancer who were previously treated with irinotecan-based frontline therapy.

Clinical practice guidelines for the surgical treatment of rectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).

In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized.

Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO)

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.

Is cancer associated thrombosis (CAT) a neglected issue? Greek management of thrombosis (GMaT) in cancer patients.

e18868Background: Cancer has multiple processes that increase thrombogenicity. Thrombosis is the 2nd cause of death in cancer patients. CAT is common, could delay anti-cancer therapy and increase c...

P-0110PHASE I TRIAL OF PANITUMUMAB IN COMBINATION WITH CISPLATIN, FLUOUROURACIL AND DOCETAXEL (MDCF) IN ADVANCED/METASTATIC GASTRIC CANCER

nd and 2 in the third dose’s levels. The median Progression Free Survival was 6.2 months (95% CI: 3.4 – 8.9 months) while the median overall survival was 12.9 (95% CI: 4.8 – 21.0) with a probability of 1 year survival of 74%. Conclusion: The Panitumumab could be safely added to the standard doses of mDCF. The combination is well tolerated, with promising efficacy results. The trial is continued as a phase II multicenter study.