PVAG (Prednisone, Vinblastine, Doxorubicin and Gemcitabine) In Elderly Patients with Intermediate or Advanced Stage Hodgkin Lymphoma: Final Results of a Phase II Study of the German Hodgkin Study Group (GHSG).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2827-2827
Author(s):  
Boris Böll ◽  
Teresa Halbsguth ◽  
Helen Görgen ◽  
Henning Bredenfeld ◽  
Hans Eich ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Advanced Stage ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Abstract 2827 About 20% of all patients diagnosed with Hodgkin lymphoma (HL) are older than 60 years. These patients have a rather poor prognosis, particularly when presenting in intermediate or advanced stages. Besides a biologically more aggressive disease, the main reason is a drastically increased toxicity of chemo- and radiotherapy resulting in a higher treatment-related mortality and insufficient dosing of the applied treatment. In the GHSG-HD9 trial, elderly patients did not benefit from the BEACOPP regimen in terms of overall survival due to a high toxicity related death rate. In order to improve tolerability, the PVAG regimen (prednisone, vinblastine, doxorubicin, and gemcitabine) was developed. This is a modification of the ABVD regimen in which bleomycin and dacarbazine were replaced by prednisone and gemcitabine. Here we report for the first time on the final analysis of this multi-center phase II study for elderly HL patients. 61 patients were recruited between 2004 and 2007. 2 patients were excluded due to histology review not confirming HL, resulting in 59 patients with intermediate- or advanced-stage HL aged between 60 and 75 years. Treatment consisted of 6 cycles PVAG in patients achieving a complete remission (CR) after 4 cycles or 8 cycles PVAG in case of partial remission (PR) after 4 cycles. Patients who did not achieve CR after the end of chemotherapy received additional radiotherapy. Primary endpoints were administration of adequate dose without excessive delays, and response rate 3 months after end of treatment. Secondary endpoints included WHO grade III/IV toxicities, and occurrence of early progression. 59 patients with a median age of 68 years were evaluated, of which 59% were male and 93% had advanced stage disease. The relative dose intensity (relative dose divided by relative chemotherapy duration) was at least 80% in 44 patients (76%). Regarding the single cycles, of which 85% started without major delay (max. 1 day), the mean relative dose of all agents was slightly decreasing over time but always exceeded 90%. WHO grade III/IV toxicities were documented in 43 patients (75%). Only 3 patients terminated CT because of excessive toxicity. 10 Patients (17%) received consolidating radiotherapy. In total, 46 patients responded with CR/CRu (78%; 95% CI: 65% to 88%), 2 with PR (3%), 2 with no change (3%) and 4 with progressive disease (7%). 3 patients died before restaging with unknown response and in 2 patients treatment outcome is unknown. With a median observation time of 37 months, 6 patients (10%) had progressive disease and 9 patients (15%) relapsed. In total, 10 patients died from relapsing or progressing HL, 2 from second malignancies (one of lung cancer after 23 months, and one of AML after 25 months) and 5 patients due to other reasons. Overall 17 patients (29%, 95% CI: 18% to 42%) have died so far. In conclusion, PVAG is safe and feasible in Hodgkin patients older than 60. The PFS indicates activity of this regimen in this poor prognosis patient cohort. However, a controlled randomized trial to determine the best treatment in this patient population is warranted. This trial was registered at www.clinicaltrials.gov as #NCT00147875. Disclosures: No relevant conflicts of interest to declare.

The Newly Developed Modified BEACOPP-Regimen (BACOPP) Is Active and Feasible in Elderly Patients with Hodgkin Lymphoma: Results of a Phase II Study of the German Hodgkin Study Group (GHSG)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2600-2600
Author(s):  
Horst Mueller ◽  
Lucia Nogova ◽  
Dennis A Eichenauer ◽  
Teresa Halbsguth ◽  
Hiltrud Nisters-Backes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Treatment Failure ◽  
Phase Ii Study ◽  
Final Analysis ◽  
Who Grade ◽  
Kaplan Meier ◽  
Advanced Stages ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Background: Approximately 20% of patients diagnosed with Hodgkin lymphoma (HL) are more than 60 years of age. These elderly patients still have a poor prognosis, especially when presenting with advanced stages and higher age. The main reason is underdosing of treatment, which is due to reduced tolerability of chemotherapy and age-related comorbidities. In the GHSG experience, elderly patients in the HD9 trial did not profit from the BEACOPP regimen in terms of overall survival, though a better HL specific freedom from treatment failure was achieved as compared to COPP/ABVD. Thus, the GHSG has developed the BACOPP regimen (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in which etoposide was omitted to improve tolerability. Further modifications were a 1 week pretreatment phase with vincristine and prednisone, a limitation of vincristine in patients older than 65 years, an increase of the anthracyclines dose, and concomitant application of erythropoietin. Here we report on the final analysis of this multi-center phase II study for elderly patients. Methods: Between 2004 and 2005, 65 patients with HL in intermediate or advanced stages aged between 60 and 75 years were recruited. Treatment consisted of 6 cycles BACOPP in patients achieving a complete remission (CR) after 4 cycles or 8 cycles BACOPP in case of PR (partial remission) after 4 cycles. The primary endpoints were protocol adherence and response rates. Secondary endpoints included WHO grade III/IV toxicities, Kaplan Meier estimates of progression free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS). Results: Sixty patients (92%) were eligible for the final analysis. The majority of treatment courses (75%) were administered according to protocol. However, there was a tendency towards reduced dosing in cycles 5 to 8, especially for patients who had reached a CR after 4 cycles of BACOPP. In total, 51 patients showed CR/CRu (85%), 2 PR (3%) and 4 progression of disease (7%). Survival estimates and their 95% confidence intervals are shown in table 1. Table 1. Kaplan-Meier rates and 95% confidence intervals (CI) for FFTF, PFS and OS. time point rate (%) CI (95%) FFTF 12 months 73 61–84 24 months 67 55–79 PFS 12 months 75 64–86 24 months 68 56–80 OS 12 months 85 76–94 24 months 76 65–87 WHO grade III–IV toxicities were documented in 52 patients (87%). With a median observation time of 33 months, 18 deaths (30%) have been observed. Seven therapy associated fatal outcomes were documented. Conclusion: The new BACOPP regimen developed for elderly HL patients shows a high CR rate (85%). The FFTF rate at 2 years is within the range known from other schedules in this patient cohort. Overall, the regimen is feasible, but the therapy-associated death rate was high in our patient cohort. Thus, further studies and new approaches are still needed to substantially improve the outcome of elderly patients with early unfavorable or advanced stage HL.

Survival Benefit of Adjuvant Radiotherapy in Elderly Patients with WHO Grade III Meningioma

2019 ◽  
Vol 131 ◽  
pp. e303-e311 ◽  
Author(s):  
Hao Zhou ◽  
Harrison X. Bai ◽  
Lilian Chan ◽  
Paul J. Zhang ◽  
Giorgos Karakousis ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Adjuvant Radiotherapy ◽  
Survival Benefit ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

scholarly journals ACTR-41. A PHASE II, SINGLE ARM STUDY OF OPTUNE® IN BEVACIZUMAB-NAIVE SUBJECTS WITH RECURRENT WHO GRADE III MALIGNANT GLIOMA

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi11-vi11
Author(s):  
Daniel O’Connell ◽  
Jose Carrillo ◽  
Xiao-Tang Kong ◽  
Beverly Fu ◽  
Daniela Bota
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Front-Line Treatment of Low-Grade Non-Follicular Non-Hodgkin Lymphoma (Final Report of Gisl LL02 Trial).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2332-2332
Author(s):  
Maria Goldaniga ◽  
Francesco Merli ◽  
Caterina Stelitano ◽  
Vincenzo Callea ◽  
Fiorella Ilariucci ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Report ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Indolent Non-follicular non-Hodgkin Lymphoma (NFo-NHL) is a group of relatively frequent lymphoproliferative diseases, nevertheless extended clinical and prognostic studies are still lacking. In 2002 the Gruppo Italiano Studio Linfomi (GISL) initiated a LL02 prospective multicenter phase II trial, with the aim to evaluate the efficacy and safety of FC combination in the first-line therapy of NFo-NHL patients younger than 70 years. Between July 2002 and September 2006, 58 adult patients (35 males and 23 females, median age 64 yrs, range 40–75) affected by NFo-NHL in active disease phase, were consecutively enrolled in 12 GISL Hematological Centres. Patients were treated with a dose of 25 mg/mq Fludarabine plus 250 mg/mq Cyclophosphamide administred intravenously daily for 3 days; each cycle was repeated every 28 days for 6 courses. During the treatment patients received oral thrimethoprim-sulphametoxazole prophylaxis. After the intermediate evaluation, 48/58 patients (82.8%) had an objective response (ORR) with a 20.7% of complete remission (CR) plus 62.1% of partial remission (PR); at the final evaluation the ORR percentage was 84.5% with a 41.4% of CR (24 pts) and 43.1% of PR (25 pts); three patients were in progressive disease (5.2%) and one in stable disease (1.7%). The median overall survival (OS) was not reached with an 88% and 84% at 12 and 24 months; the progression free survival (PFS) was 89% and 77% and the event free survival (EFS) was 81% and 66% at 12 and 24 months respectively.About the toxicity profile, the major toxicity was hematological with a 18% cases of WHO grade III or IV anemia, 40% leucopenia, 33% neutropenia and 10% piastrinopenia. The 12% of patients had an infective episode wich a 7.7% of WHO grade III–IV.In conclusion the FC chemotherapy is a useful chance for advanced untreated non follicular low-grade NHL, with an optimal ORR, CR and PFS. The crucial point of FC remains OS, that not seems to be significantly improved in comparison with fludarabine alone or with standard therapy, even though the better quality of responses; Rituximab plus FC association is growing in literature as the probably key to find a real improvement also in this aspect.

BACOPP-D - An Etoposide-Free Dose-Escalated Polychemotherapy Regimen in Advanced Hodgkin Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2317-2317
Author(s):  
Ralph Naumann ◽  
Katrin Wetzko ◽  
Annette Haenel ◽  
Kai Friedrichsen ◽  
Ernst Zschuppe ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Observation Time ◽  
Hypopharyngeal Carcinoma ◽  
High Dose ◽  
Who Grade ◽  
Fdg Uptake ◽  
Pet Scans ◽  
Grade Iii

Abstract Introduction: The development of the escalated BEACOPP regimen let to an improved outcome in patients with advanced Hodgkin Lymphoma (HD9 study of the GHSG). However, the application of high dose etoposide (cumulative 4,8 g/m2 per 8 cycles) seems to be associated with an increased incidence of secondary MDS and AML, respectively. Therefore, the aim of our multicenter pilot study was to evaluate the efficacy and toxicity of the etoposide free as well as dose intensified BACOPP-D protocol. Methods: Since May 2000 a total of 115 patients with Hodgkin Lymphoma (HL) stage IIB, III, and IV were treated with BACOPP-D which included cyclophosphamide 1250 mg/m2 (d1), adriamycin 25 mg/m2 (d1+2), dacarbazine 250 mg/m2 (d1-3), procarbazine 100 mg/m2 (d1-7), prednisolone 40 mg/m2 (d1-14), bleomycin 10 mg/m2 (d8) and vincristine 1,4 mg/m2 (maximum 2 mg, d8) at three-weekly intervals with granulocyte colony-stimulating factor (G-CSF). A consolidating involved field radiation (30 Gy) was performed only in patients who achieved less than CR following chemotherapy. Post-treatment follow-up included PET imaging. Results: Until now 97 patients (median age 35 years, range 17-65; 61 male, 36 female) are assessable for toxicity and treatment outcome. We analyzed the acute toxicity for 728 cycles of BACOPP-D. CTC/WHO grade III/IV haematological toxicities per patient were observed as follows: leukopenia 93%, anemia 39%, and thrombocytopenia 33%. CTC grade III/IV non-haematological side effects included documented infection (4%) and lung toxicity (one patient). A total of 85 patients (88%) achieved complete remission, 9 patients (9%) achieved partial remission, three patients (3%) had progressive disease. At a median observation time of 39 months (0,9-77 months), five patients have relapsed, and nine deaths were documented (4 HL-specific and 3 treatment related deaths, 1 death due to ruptured Meckel diverticulum with peritonitis, one 65 year-old woman died in CR following myocardial infarction). One patient developed a second neoplasia (hypopharyngeal carcinoma in an alcoholic). The overall survival and freedom from treatment failure rates at 39 months were 91% and 85%, respectively. FDG-PET scans after BACOPP-D chemotherapy were performed in 68 of 97 patients. PET scans revealed no increased FDG uptake in 48/68 patients (71%), in 20 patients (29%) increased FDG uptake was detected. In the group of patients with increased FDG uptake, one patient developed progressive disease and four patients relapsed. In the group with PET-negative findings no patient relapsed. Diskussion: BACOPP-D regimen appears as a feasible and effective treatment which induced a complete morphologic and metabolic remission in a high proportion of patients with advanced HL. The treatment was associated with moderate acute toxicity. No secondary AML or MDS occurred until now.

Phase II study: WBRT ±temozolomide (TMZ) in patients with multiple brain metastases from non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13008-e13008
Author(s):  
C. Marosi ◽  
K. Elandt ◽  
M. Preusser ◽  
K. Dieckmann ◽  
M. Nevinny ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Recursive Partitioning ◽  
Whole Brain Radiotherapy ◽  
Class Ii ◽  
Morbidity And Mortality ◽  
Who Grade ◽  
Multiple Brain Metastases

e13008 Background: Brain metastases cause increasingly morbidity and mortality in patients with NSCLC. In a multicentric Austrian phase II study, we investigated feasibility and toxicity of the addition of temozolomide to whole brain radiotherapy (WBRT) in patients with multiple brain metastases of NSCLC. Methods: Consenting patients with previously untreated, multiple, and measurable brain metastases from histologically confirmed NSCLC were eligible if they were 18 years or older, were at least in RPA (recursive partitioning analysis class) class II and showed adequate organ function. Treatment consisted of WBRT (arm A) +TMZ 75mg/m2 during radiation, followed at day 28 by TMZ 100 mg/m2 day 1–14, q28 for six cycles (arm B). The primary endpoint was objective radiographic response in CNS 10 weeks after the end of WBRT. Results: 35 patients (14 women) aged 35 to 86 years, median 65 years were randomized. Eight patients were in RPA class I and 27 were in RPA class II. 13 patients were enrolled in arm A and 22 in arm B. Toxicity was mainly haematological with WHO grade 3 and 4 thrombocytopenia observed in 0/13 versus 3/22 patients, leucocytopenia in 0/13 versus 1/22 patients, and lymphocytepenia in 12/13 and 7/22 patients respectively. No severe nonhematologic toxicity occured in arm A, whereas two episodes of transient hepatic toxicity were reported in arm B. 10/13 patients of arm A and 13/22 patients of arm B showed progressive disease and dropped out of study before restaging 10 weeks after completion of WBRT. Two patients of arm A had progressive disease in CNS, all other progresses noted were systemic. At restaging there were 2 PR, 1 SD in arm A, and 1 CR, 3 PR, 6 SD in arm B. Median time to progression was 40 days in arm A and 74 days in arm B (p = 0.027). Conclusions: The addition of temozolomide to WBRT in patients with brain metastases of NSCLC yielded acceptable toxicity and promising activity, although systemic progression remained the main cause of morbidity and mortality. [Table: see text]

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