Athanasios Karampeazis

Pemetrexed versus erlotinib in pretreated patients with advanced non–small cell lung cancer: A Hellenic Oncology Research Group (HORG) randomized phase 3 study

In this superiority study, pemetrexed was compared with erlotinib in pre‐treated patients with metastatic non–small cell lung cancer (NSCLC).

Docetaxel vs. vinorelbine in elderly patients with advanced non--small-cell lung cancer: a hellenic oncology research group randomized phase III study.

BACKGROUND/PURPOSE This study compared front-line treatment with docetaxel or vinorelbine in elderly patients with advanced/metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Chemotherapy-naive patients with inoperable stage IIIB and stage IV NSCLC who were > 65 years of age with performance status (PS) of 0-2 were enrolled. Patients were assigned to receive either docetaxel 38 mg/m(2) or vinorelbine 25 mg/m(2) by intravenous (I.V.) infusion on days 1 and 8 every 3 weeks. RESULTS One hundred thirty elderly patients were enrolled in the study (docetaxel n = 66 and vinorelbine n = 64 patients). The objective response rate was 12.1% and 14.1% in patients treated with docetaxel and vinorelbine, respectively (2P = .799). The median time to tumor progression (TTP) was 2.33 and 1.9 months (2P = .298) and the median overall survival (OS) was 6.07 and 3.87 months (2P = .090) in the docetaxel and vinorelbine arms, respectively. Grade 3/4 neutropenia occurred in 4.5% and 29.7% of patients in the docetaxel arm and vinorelbine arm, respectively (2P < .001). Febrile neutropenia occurred in 1.5% and 1.6% of patients in the docetaxel arm and the vinorelbine arm, respectively (2P = .950) and the use of granulocyte colony-stimulating factor (G-CSF) was more frequent in patients treated with vinorelbine (37.1% vs. 22.5%; 2P < .001). There were no deaths from toxicity. Nonhematologic toxicity was mild. CONCLUSIONS Docetaxel has an efficacy comparable to that of vinorelbine as first-line treatment in elderly patients with NSCLC and has an acceptable toxicity profile. The trial was closed prematurely because of low accrual, thus limiting the strength of the conclusions derived.

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.

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/m2, 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/m2 for gemcitabine and 450 mg/m2 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.

Advanced non-small-cell lung cancer in the elderly.

Systemic chemotherapy provides improvement in both survival and quality of life for patients with advanced non-small-cell lung cancer (NSCLC). Elderly patients have more comorbidities and tend to tolerate more poorly aggressive chemotherapy and radiation therapy than younger individuals. Our purpose in this article is to summarize recent studies of single-agent chemotherapy and combination regimens with cytotoxic or targeted therapies in the management of elderly patients with advanced NSCLC. We have reviewed the available evidence in the literature to gauge the results of therapy for elderly patients with lung cancer. We found that single-agent chemotherapy remains the standard of care for nonselected elderly patients. Retrospective analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with increased but acceptable toxicity for elderly patients. Therefore, the outcomes in the fit elderly mirror results observed in younger patients, although toxicity is generally greater.

Docetaxel plus gemcitabine versus gemcitabine in elderly patients with advanced non-small cell lung cancer and use of a geriatric assessment: Lessons from a prematurely closed Hellenic Oncology Research Group randomized phase III study

OBJECTIVES To compare first-line treatment with docetaxel plus gemcitabine (DG) versus gemcitabine (G) in elderly patients with advanced/metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Chemotherapy-naïve patients with inoperable stage IIIB/IV NSCLC, ≥70years, with an ECOG performance status (PS) of 0-2 were enrolled. Patients were stratified by PS and disease stage and randomized to either DG (docetaxel 30mg/m2 plus gemcitabine 900mg/m2 i.v.) or G (gemcitabine 1200mg/m2 i.v.) on days 1 and 8, every 3weeks. The studys primary end-point was overall survival (OS). RESULTS In this prematurely closed study, 106 patients with a median age of 75years (range, 70-92) were enrolled (DG: n=54; G: n=52); 77 (73%) had stage IV disease and 18 (17%) a PS of 2. There was no difference in terms of median OS (14.6 vs 12.2months; p=0.121), progression-free survival (PFS) (3.4 vs 2.6months; p=0.757) and overall response rate (26.0% vs 15.4%; p=0.233) between DG and G arm, respectively. Patients with an Instrumental Activities of Daily Living (IADL) score<7 had significantly lower median OS (7.6 vs 15.4months; p=0.002) and median PFS (1.7 vs 4.4months; p=0.009) than patients with higher IADL score. The regimens were well tolerated with no significant difference in severe toxicity. CONCLUSION DG and G demonstrated comparable efficacy in elderly patients with NSCLC and high IADL score was correlated with superior clinical outcome.

Non-Platinum-Based First-Line Followed by Platinum-Based Second-Line Chemotherapy or the Reverse Sequence in Patients with Advanced Non-Small Cell Lung Cancer: A Retrospective Analysis by the Lung Cancer Group of the Hellenic Oncology Research Group

Background: Non-platinum-containing regimens have been proposed as alternatives to platinum-based doublets in the first-line treatment of patients with non-small cell lung cancer (NSCLC). However, conflicting results about their equivalence have been reported. Methods: We reviewed the records of patients enrolled in randomized controlled first-line trials conducted by the Hellenic Oncology Research Group from February 1997 to September 2006. The outcome of patients treated with first-line non-platinum-based chemotherapy who received platinum-based chemotherapy upon progression (cohort A) or platinum-based first-line chemotherapy followed by non-platinum-containing second-line chemotherapy (cohort B) was retrospectively analyzed. Results: Two-hundred and sixty-seven patients were identified in cohort A, and 123 in cohort B. Median follow-up time was 12.5 and 15.7 months for cohorts A and B. A significantly higher response rate and time to tumor progression (TTP) was recorded for patients treated with platinum-based compared to those receiving non-platinum-based first-line chemotherapy (45.5 vs. 21.3%, p < 0.0001 and 5.8 vs. 3.1 months, p= 0.002, respectively). Platinum-based regimens administered as second-line treatment resulted in a 13.1% response rate. TTP for second-line chemotherapy did not differ significantly between the two cohorts. Median overall survival was 13.3 and 15.7 months for cohorts A and B (p = 0.538). Conclusion: Both sequences resulted in similar efficacy in terms of overall survival. Encouraging median survival was achieved for selected patients with NSCLC who received both first- and second-line chemotherapy.

A dose escalation study of the biweekly administration of paclitaxel, oxaliplatin and capecitabine in patients with advanced solid tumors

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum-tolerated doses of the paclitaxel, oxaliplatin (LOHP) and capecitabine combination in patients with advanced solid tumors. Patients and Methods: Patients received escalating doses of paclitaxel (starting dose 100 mg/m2) and LOHP (starting dose 40 mg/m2) on days 1 and 15 and capecitabine (starting dose 800 mg/m2/day) on days 1–7 and 15–21 every 28 days. DLTs were evaluated in the first cycle. Results: Sixteen patients were treated at four dose-escalating levels. Eleven (68.7%) patients had received two or more prior chemotherapy regimens. The DLT level was reached at paclitaxel 110 mg/m2, LOHP 50 mg/m2 and capecitabine 1,000 mg/m2/day. DLTs due to grade 2–3 neutropenia resulted in treatment delays. No febrile neutropenia or treatment-related death occurred. Grade 2–3 neutropenia occurred in 3 (19%) patients each, grade 2–4 fatigue affected 6 (37.5%) patients, and grade 2–3 neurotoxicity was observed in 2 (12.5%) and 1 (6%) patients, respectively. Two partial responses and four disease stabilizations were achieved. Conclusion: The recommended doses for phase II studies are paclitaxel 100 mg/m2 and LOHP 50 mg/m2 on days 1 and 15 and capecitabine 1,000 mg/m2/day on days 1–7 and 15–21 every 4 weeks. This regimen is well tolerated and merits further evaluation.

Efficacy of panitumumab in older patients with metastatic colorectal cancer: a retrospective analysis using the database of the Hellenic Oncology Research Group (HORG)

BACKGROUND Although colorectal cancer (CRC) is a disease of the older patients, older patients are under-represented from randomized trials. Herein we conducted a retrospective analysis for the effect of panitumumab in the management of older patients (≥65 years) patients with metastatic CRC (mCRC) in the Hellenic Oncology Research Groups (HORG) database. METHODS Τhe efficacy of panitumumab-based chemotherapy as front-line treatment in older patients with mCRC was assessed. RESULTS In total, 110 older patients with KRAS exon 2 wild type tumors were treated with chemotherapy plus panitumumab. The median age was 74 years; 69.9% of the patients were male, with left-sided primary tumors (78.2%), ECOG Performance Status 0-1 (95.4%) and median number of metastatic sites 2. Sixty-two (Overall Response Rate-ORR: 56.4%; 95% CI: 48.8%-68.1%) achieved an objective response, while 21 (19.1%) had stable disease. Median Progression free survival (PFS) was 9.4 months (95% CI: 7.8-11.0 months) and median Overall survival (OS) 23.0 months (95% CI: 20.6-25.3 months). Additionally, a statistically significant difference in ORR (62.7% vs. 33.3%; p = .014), median PFS (12.9 vs. 5.7 months; p = .001) and median OS (31.6 vs. 16.7 months; p < .001) was observed in patients with left-sided compared to right-sided primary tumor. There was no treatment-related death. Grade 3-4 toxicities were neutropenia (8.9%) and diarrhea (14.5%) whereas skin rash grade 2 or 3 was recorded in 41.1% and 10.7%, respectively. CONCLUSIONS The results of this retrospective study provide the evidence that combination chemotherapy plus panitumumab is active and well tolerated in older patients with mCRC.

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.