Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). METHODS: Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. RESULTS: In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3-126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61-1.55); P = 0.647]. Eighty DFS events (3M N = 41; 6M N = 39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68-1.63, P = 0.829). For stage III patients, 314 DFS events (3M N = 161 and 6M N = 153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81-1.42, P = 0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54-2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59-1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74-1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70-1.44). CONCLUSIONS: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01308086.

Efficacy and treatment tolerance in older patients with NSCLC: a meta-analysis of five phase III randomized trials conducted by the Hellenic Oncology Research Group.

BACKGROUND: Approximately 50% of newly diagnosed cases of non-small-cell lung cancer (NSCLC) are observed in patients >65 years, while 30%-40% of cases occur in patients >70 years. PATIENTS AND METHODS: The objective of the current study was to determine (i) the number of elderly (>70 years) patients with advanced/metastatic NSCLC enrolled in phase III trials of the Hellenic Oncology Research Group, (ii) the treatment-related toxicity observed in these patients compared with their younger counterparts, and (iii) the differences in terms of response rate, time to tumor progression (TTP), and overall survival (OS) between younger and older patients. RESULTS: Pooled data from five clinical trials including 1845 patients were analyzed; 1421 (77%) and 424 (23%) were <70 years and ≥70 years, respectively. No difference was observed in terms of the overall response rate and TTP. There was an OS difference between young and older patients, with higher risk for death in older patients. However, when the analysis was carried out after omitting a trial that showed a different trend, no difference was observed. Older patients experienced higher toxicity. CONCLUSIONS: This report supports the feasibility of chemotherapy treatment for older NSCLC patients. Optimization of treatment of older NSCLC patients requires the design of prospective older-specific phase III trials for these patients.

Clinical outcome of elderly patients with metastatic colorectal cancer treated with FOLFOXIRI versus FOLFIRI: Subgroup analysis of a randomized phase III trial from the Hellenic Oncology Research Group (HORG).

BACKGROUND: A subgroup analysis of oxaliplatin (LOHP)+irinotecan (CPT-11)+5-fluorouracil (5FU) and leucovorin (LV) (FOLFOXIRI regimen) versus irinotecan+5FU/LV (FOLFIRI regimen) as first-line treatment of patients >65 years old with metastatic colorectal cancer is presented. PATIENTS AND METHODS: Eighty-two (56%) and 75 (55%) patients with metastatic colorectal cancer aged >65 years were enrolled in the FOLFOXIRI and FOLFIRI regimen, respectively. RESULTS: There was no statistically statistical difference in terms of overall survival or time-to-tumor progression between young and aged patients between the two chemotherapy arms. The objective response rate was significantly lower in older patients treated with FOLFOXIRI (32% vs. 52%; OR: 1.45, 95% CI: 1.06-2.09; p=0.03). Elderly patients experienced a significantly higher incidence of grade 3/4 diarrhea compared to younger patients, irrespectively of the chemotherapy regimen (p=0.005 for FOLFIRI; p=0.017 for FOLFOXIRI). Dose reductions and treatment delays were more frequent in the FOLFOXIRI arm. CONCLUSION: FOLFOXIRI does not seem to offer substantial benefit compared to FOLFIRI regimen in elderly patients with metastatic colorectal cancer.

A dose escalation study of gemcitabine plus pemetrexed administered biweekly in patients with solid tumors.

PURPOSE: The study aimed to determine the maximum tolerated doses (MTDs) and identify the dose-limiting toxicities of the biweekly administration of pemetrexed plus gemcitabine in patients with solid tumors. PATIENTS AND METHODS: Patients with advanced malignancies were treated with escalated doses of gemcitabine and pemetrexed (starting doses 1,250 and 300 mg/m(2), respectively) both given on days 1 and 15 in cycles of 4 weeks. RESULTS: Forty-one patients were treated at 7 dose levels. The MTD was reached at the dose of 1,750 mg/m(2) for gemcitabine and 450 mg/m(2) for pemetrexed. Dose-limiting events were grade IV neutropenia, febrile neutropenia and treatment delay due to grade III hematological toxicities. One partial response in a pretreated patient with ovarian cancer was observed, while 4 other patients experienced stable disease. CONCLUSIONS: The biweekly administration of gemcitabine plus pemetrexed at the recommended MTDs is safe, well tolerated and demonstrates antitumor activity which merits further evaluation in phase II studies.

A dose escalation study of biweekly oral vinorelbine and gemcitabine in patients with solid tumors.

PURPOSE: To determine the maximum tolerated doses (MTDs) and the dose-limiting toxicities of a biweekly administration of oral vinorelbine and gemcitabine in patients with advanced solid tumors. PATIENTS AND METHODS: Twenty-eight patients with advanced stage solid tumors were enrolled, and 12 (42.9%) of them were chemotherapy naive. Escalating doses of vinorelbine (50-70 mg/m2 per os) and gemcitabine (800-1,000 mg/m2 as a 30-min intravenous infusion) were administered on days 1 and 15 in 4-week cycles. RESULTS: MTDs were reached at 70 mg/m2 p.o. for vinorelbine and 900 mg/m2 for gemcitabine. Grade 4 neutropenia, febrile neutropenia, grade 4 nausea/vomiting and treatment delay due to grade 3 neutropenia were the dose-limiting events during the first cycle of chemotherapy. A total of 94 chemotherapy cycles were administered with only one episode of febrile neutropenia and no toxic deaths. Severe (grade 3-4) neutropenia occurred in 10% of cycles while non-hematological toxicity was mild with grade 2-3 asthenia occurring in 17 (18%) cycles. Objective responses were achieved in patients with prostate and non-small cell lung cancer. CONCLUSIONS: The combination of biweekly oral vinorelbine (70 mg/m2) and gemcitabine (900 mg/m2) is a well-tolerated regimen with promising results in patients with advanced solid tumors.