Periklis Tsekeris

Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: A randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG)

BACKGROUND Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. PATIENTS AND METHODS To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response. RESULTS 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded. CONCLUSION Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.

Induction chemotherapy with cisplatin, epirubicin, and paclitaxel (CEP), followed by concomitant radiotherapy and weekly paclitaxel for the management of locally advanced nasopharyngeal carcinoma. A Hellenic Cooperative Oncology Group phase II study.

Background:Clinical research on the treatment of nasopharyngeal cancer (NPC) has been focused primarily on the reduction of incidence of the development of distant metastases as well as the improvement of locoregional control.Patients and Methods:Untreated patients with stage IIB–IVB nonmetastatic NPC were treated with three cycles of induction chemotherapy (IC) consisting of epirubicin 75 mg/m2 followed by paclitaxel 175 mg/m2 as 3-h infusion on day 1 and cisplatin 75 mg/m2 on day 2 every 3 weeks, followed by concomitant radiation therapy (70 Gy), and chemotherapy (CCRT) with weekly paclitaxel 60 mg/m2.Results:From November 1999 until April 2003, 47 patients entered the study. Complete response rate post IC therapy was 15%, which was raised to 66% after the completion of CCRT. The most frequent side effect from IC was myelotoxicity (55%), whereas stomatitis and xerostomia were the most pronounced (grade 3, 4) toxicities during CCRT. The presence of Epstein-Barr virus (EBV) was detected either by in situ hybridization in tumor tissue sections or by polymerase chain reaction in the peripheral blood in 37 out of 46 patients tested (80%). All three histological types were associated with the presence of EBV. After a median follow-up of 23.5 months, median time to treatment failure was 17.9 months, whilst median survival has not been reached yet.Conclusion:IC followed by CCRT is feasible and produces durable complete responses in the majority of patients with NPC. The case detection rate of EBV in this study appears to be similar to that reported from endemically infected regions.Hintergrund:Die klinische Forschung in der Behandlung des Nasopharynxkarzinoms (NPC) fokussiert vorrangig auf die Reduktion von Fernmetastasen und die Verbesserung der lokoregionären Kontrolle.Patienten und Methodik:Unbehandelte Patienten mit nicht metastasiertem NPC wurden mit drei Zyklen Induktionschemotherapie (IC), bestehend aus Epirubicin 75 mg/m2 und Paclitaxel 175 mg/m2 als 3-stündige Infusion an Tag 1 sowie Cisplatin 75 mg/m2 an Tag 2 alle 3 Wochen, gefolgt von simultaner Radiochemotherapie (RCT) mit 70 Gy und 60 mg/m2 Paclitaxel wöchentlich, behandelt.Ergebnisse:Von November 1999 bis April 2003 wurden 47 Patienten in die Studie aufgenommen. Die Rate an kompletten Remissionen nach IC betrug 15% und konnte nach Abschluss der konsekutiven RCT auf 66% angehoben werden. Die häufigste Nebenwirkung der IC war Myelotoxizität (55%), der RCT dagegen Stomatitis und Xerostomie (Grad 3, 4). Eine Epstein-Barr-Virus-(EBV-)Positivität wurde durch In-situ-Hybridisierung in Tumorgewebe oder Polymerase-Kettenreaktion im peripheren Blut in 37 von 46 Fällen (80%) nachgewiesen. Alle drei histologischen Typen gingen mit EBV-Positivität einher. Bei einer medianen Nachbeobachtungszeit von 23,5 Monaten betrug die mediane Zeit bis zum Therapieversagen 17,9 Monate; das mediane Überleben hingegen ist noch nicht determiniert.Schlussfolgerung:IC, gefolgt von RCT, geht bei der Mehrzahl der Patienten mit NPC mit lang anhaltenden Komplettremissionen einher. Die Kontaminationsrate mit EBV in dieser Studie ähnelt der endemisch betroffener Regionen.

Induction Chemotherapy with Cisplatin, Epirubicin, and Paclitaxel (CEP), Followed by Concomitant Radiotherapy and Weekly Paclitaxel for the Management of Locally Advanced Nasopharyngeal Carcinoma

Background:Clinical research on the treatment of nasopharyngeal cancer (NPC) has been focused primarily on the reduction of incidence of the development of distant metastases as well as the improvement of locoregional control.Patients and Methods:Untreated patients with stage IIB–IVB nonmetastatic NPC were treated with three cycles of induction chemotherapy (IC) consisting of epirubicin 75 mg/m2 followed by paclitaxel 175 mg/m2 as 3-h infusion on day 1 and cisplatin 75 mg/m2 on day 2 every 3 weeks, followed by concomitant radiation therapy (70 Gy), and chemotherapy (CCRT) with weekly paclitaxel 60 mg/m2.Results:From November 1999 until April 2003, 47 patients entered the study. Complete response rate post IC therapy was 15%, which was raised to 66% after the completion of CCRT. The most frequent side effect from IC was myelotoxicity (55%), whereas stomatitis and xerostomia were the most pronounced (grade 3, 4) toxicities during CCRT. The presence of Epstein-Barr virus (EBV) was detected either by in situ hybridization in tumor tissue sections or by polymerase chain reaction in the peripheral blood in 37 out of 46 patients tested (80%). All three histological types were associated with the presence of EBV. After a median follow-up of 23.5 months, median time to treatment failure was 17.9 months, whilst median survival has not been reached yet.Conclusion:IC followed by CCRT is feasible and produces durable complete responses in the majority of patients with NPC. The case detection rate of EBV in this study appears to be similar to that reported from endemically infected regions.Hintergrund:Die klinische Forschung in der Behandlung des Nasopharynxkarzinoms (NPC) fokussiert vorrangig auf die Reduktion von Fernmetastasen und die Verbesserung der lokoregionären Kontrolle.Patienten und Methodik:Unbehandelte Patienten mit nicht metastasiertem NPC wurden mit drei Zyklen Induktionschemotherapie (IC), bestehend aus Epirubicin 75 mg/m2 und Paclitaxel 175 mg/m2 als 3-stündige Infusion an Tag 1 sowie Cisplatin 75 mg/m2 an Tag 2 alle 3 Wochen, gefolgt von simultaner Radiochemotherapie (RCT) mit 70 Gy und 60 mg/m2 Paclitaxel wöchentlich, behandelt.Ergebnisse:Von November 1999 bis April 2003 wurden 47 Patienten in die Studie aufgenommen. Die Rate an kompletten Remissionen nach IC betrug 15% und konnte nach Abschluss der konsekutiven RCT auf 66% angehoben werden. Die häufigste Nebenwirkung der IC war Myelotoxizität (55%), der RCT dagegen Stomatitis und Xerostomie (Grad 3, 4). Eine Epstein-Barr-Virus-(EBV-)Positivität wurde durch In-situ-Hybridisierung in Tumorgewebe oder Polymerase-Kettenreaktion im peripheren Blut in 37 von 46 Fällen (80%) nachgewiesen. Alle drei histologischen Typen gingen mit EBV-Positivität einher. Bei einer medianen Nachbeobachtungszeit von 23,5 Monaten betrug die mediane Zeit bis zum Therapieversagen 17,9 Monate; das mediane Überleben hingegen ist noch nicht determiniert.Schlussfolgerung:IC, gefolgt von RCT, geht bei der Mehrzahl der Patienten mit NPC mit lang anhaltenden Komplettremissionen einher. Die Kontaminationsrate mit EBV in dieser Studie ähnelt der endemisch betroffener Regionen.

Pure Small Cell Carcinoma of the Prostate: A Case Report and Literature Review

Primary small cell carcinoma of the prostate (SCPCa) is a rare pathologic entity with unique clinical features and a poor prognosis. We present a case of a patient diagnosed with pure SCPCa treated with a combined chemo-radiotherapeutic approach. Pathological findings showed that the neoplastic cells exhibited positivity for pancytokeratin, synaptophysin, thyroid transcription factor-1 and CD56. Immunostaining for prostate-specific antigen was negative, while serum prostate-specific antigen was within normal limits. We review the available literature to gain additional information about diagnosis, treatment and prognosis of pure SCPCa.

Paclitaxel, cisplatin, leucovorin, and continuous infusion fluorouracil followed by concomitant chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck: a Hellenic Cooperative Oncology Group Phase II Study.

The primary objective of this phase II study was to access the complete response (CR) rate to a new innovative induction regimen in patients with locally advanced head and neck cancer (LA-HNC). From October 2000 until October 2003 a total of 38 eligible patients (33 men and 5 women) entered the study. The large majority of them presented with a performance status of 0–1 and with clinical stage IV disease. Treatment consisted of three cycles of induction chemotherapy (IC) with paclitaxel 175 mg/m2 in a 3-h infusion on d 1, leucovorin (LV) 200 mg/m2 over 20 min immediately followed by FU 400 mg/m2 bolus and then 600 mg/m2 as a 24-h continuous infusion on d 1 and 2 and a cisplatin 75 mg/m2 over 1-h infusion on d 2 every 3 wk. This was then followed by radiation (70 Gy) and weekly cisplatin 40 mg/m2. After the completion of IC, 6/38 (16%) patients had CR. The CR rate was increased to 66% post-concomitant chemoradiotherapy (CCRT). Neutropenia (37.5%), pain (62%), nausea/vomiting (21%), and alopecia (79%) were the most frequent side effects during IC. The most pronounced toxicities during chemoradiotherapy were stomatitis (62.5%) and xerostomia (53%). Median time to progression was 11.0 mo and median survival 16.7 mo. One- and 2-yr survival rates were 73% and 38%, respectively. In conclusion, this novel induction regimen is active, is well tolerated, and can be successfully followed by CCRT with weekly cisplatin. CCRT should remain standard treatment for patients with LA-HNC. Novel induction combinations, such as that reported in the present study, should be evaluated in combination with CCRT only in the context of clinical trials.