Three versus four cycles of neoadjuvant gemcitabine cisplatin for muscle invasive bladder cancer (MIBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16524-e16524
Author(s):  
Catherine Kendall Major ◽  
Michael Brandon Williams ◽  
Mark T. Fleming
Keyword(s):  
Radical Cystectomy ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Muscle Invasive ◽  
Dose Dense

e16524 Background: The standard of care for MIBC is neoadjuvant (NAC) cisplatin-based chemotherapy with either 3-4 cycles of dose dense MVAC or 4 cycles of gemcitabine/cisplatin (GC) followed by radical cystectomy. However, due to toxicity some patients are unable to complete intention to treat full course chemotherapy. We aim to identify any variation in overall survival (OS) and progression-free survival (PFS) with 3 vs 4 cycles of neoadjuvant GC in the setting of miUCB. We hypothesize that there will be a statistically significant difference in OS and PFS with three vs four cycles of neoadjuvant GC. Methods: A consecutive retrospective chart review of patients with MIBC treated with three or four cycles of neoadjuvant cisplatin-based chemotherapy from 2009-2020 was performed. R Studio was used to generate Kaplan-Meier curves representing OS and PFS with p-values. Results: One hundred and twenty-one patients were identified. Patient characteristics are described in the table below. Eighty-six patients received 4 cycles of GC and thirty-five patients received 3 cycles. Ninety-five patients proceeded to cystectomy: 93 received a radical cystectomy, 1 received a partial cystectomy, and 1 was aborted due to positive lymph nodes. There was a statistically significant difference in OS between those who got 3 or 4 cycles (p=0.03) and PFS (p=0.014). Median OS for those who got 3 cycles and 4 cycles was 52 months and 92 months respectively. Conclusions: Toxicity can preclude patients from receiving four cycles of GC and this study demonstrates a significant difference in overall OS and PFS between those who receive 3 vs 4 cycles of GC.[Table: see text]

Outcomes in AML patients receiving HMA + venetoclax combination with prior HMA exposure.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19011-e19011
Author(s):  
Bakos Keegan Jonathan ◽  
Dena Blanding ◽  
Christopher Andrew Rangel ◽  
Sarah Pasyar ◽  
Elizabeth Goodwin Hill ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Clinical Laboratory ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Poor Response ◽  
Patient Characteristics ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Poor Outcomes

e19011 Background: Venetoclax (Ven) is a BCL-2 inhibitor approved in combination with hypomethylating agents (HMAs) in newly diagnosed AML patients who are not candidates for intensive induction based on impressive response rates (CR+CRi of 66.4%) and median overall survival (14.7 months) compared to HMA therapy alone (DiNardo CD, NEJM, 2020). Ven was also used in combination with 10 days of a HMA (Decitabine) in a phase II study. In the subgroup of patients with relapsed AML, some of which previously received HMA, the ORR, CR+CRi, and median OS were 62%, 42%, and 7.8 months respectively. (DiNardo CD, Lancet, 2020). To our knowledge there are no studies specifically looking at patients with AML receiving HMA + Ven with previous exposure to a HMA agent. Methods: We conducted a single center retrospective study of AML patients who received HMA + Ven therapy after previously receiving a HMA agent. Baseline demographic, clinical, laboratory, pathology, and outcomes data were collected by retrospective chart review. Response criteria was determined by 2017 ELN recommendations. Kaplan Meier was constructed to summarize time to event data. Results: A total of 17 patients were identified that met these criteria. 7 patients (41%) had progressed on prior HMA treatment, 11 patients (65%) received prior intensive chemotherapy, and 5 patients (29%) received previous Allogenic SCT prior to HMA+Ven therapy. 10 patients (59%) had either a TP53 mutation or 17p deletion and 11 patients (65%) had complex cytogenetics (≥ 3 cytogenetic abnormalities). Other patient characteristics are included in table below. For the entire cohort, the ORR (CR, CRi, PR) was 41% and the CR/CRi rate was 6%; The ORR in the following subgroups for previous HMA failure, TP53 mutation/17p deletion, and complex cytogenetics were 14%, 30%, and 36% respectively. The median Progression free survival and overall survival for the entire cohort was 2 months (1-4 months 95% CI) and 3 months (1-5 months, 95% CI) respectively. 15 patients (88%) were deceased and all deaths were attributed to AML (12/15) or infection (3/15). None of the patients went on to receive an Allogenic SCT. Conclusions: Although a limited sample size which includes many patients with a TP53/17p aberration, complex cytogenetics, Allogenic SCT relapse, and/or heavily pre-treated AML, this data describes poor outcomes in patients receiving HMA+Ven after previous HMA exposure. Patients with previous HMA failure in particular had a poor response rate. None of the patients received 10 day decitabine and it is unclear if this had any effect on the results. It would be beneficial to supplement this data with experience from multiple centers. Patient Characteristics (N = 17).[Table: see text]

scholarly journals Glioblastoma and increased survival with longer chemotherapy duration.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13006-e13006
Author(s):  
Dory Abou-Jaoude ◽  
Joseph A Moore ◽  
Matthew B Moore ◽  
Philip Twumasi-Ankrah ◽  
Elizabeth Ablah ◽  
...  
Keyword(s):  
Sample Size ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Science Data ◽  
Chi Square ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Regional Referral Center

e13006 Background: The 5-year survival for patients (pts) with glioblastoma (GBM) is low at approximately 3%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remain the standard of care. The optimal duration of therapy with TMZ is unknown, though treatment periods of 6 months (mo), 12 mo and longer have been utilized. Whether or not there is a benefit with longer treatment duration is controversial. Methods: A retrospective chart review of all pts diagnosed with GBM who were treated at a regional referral center was conducted with data obtained from their electronic medical records. These pts were treated with TMZ for up to 2 years between January 1, 2002 and December 31, 2011. Survival was calculated as the time from initial surgical diagnosis until death. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) as well as the overall survival (OS) distribution of pts after treatment. The results were compared to historical controls and data from previous clinical trials of pts treated up to 1 year. Results: Data from 56 pts were evaluated, the majority of whom had gross total resection and had external pathology review confirming the diagnosis of GBM. The OS probability was 55.4% (SE = 0.068) at 1 year, 26.9% (SE = 0.067) at 2 years and 20.1% (SE = 0.065) at 3 years. The median PFS time in this study group was 8 mo (95% CI = 4.0 – 9.0 mo). The probability of no progression at 2 years was 8.6% (SE = 0.05). Seven pts (12.5%) were treated with TMZ for 2 years. The probability of disease progression at 2 years among these pts was 33.3% with a median time-to-progression of 20 mo (95% CI = 5.0-28.0). These patients showed an increased survival probability at 3 years compared to pts who did not receive the 2 year treatment of TMZ (log-rank test Chi-square = 12.4, p = 0.0004). Conclusions: This analysis suggests that there may be an advantage for a longer duration of TMZ therapy in pts with GBM. In this review, treatment with TMZ for 2 years was associated with an increased survival benefit. While we consider the sample size to be too small for generalization, a prospective/multicenter study with a larger sample size might better evaluate the question of duration of TMZ therapy, particularly if both clinical and basic science data are paired.

Full-dose irinotecan plus platinum (IP) with concurrent thoracic radiotherapy (C-TRT) in unresectable locally advanced non-small cell lung cancer (LA-NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17547-e17547
Author(s):  
Jun Zhang ◽  
Tithi Biswas ◽  
Daniel B Fried ◽  
Julian Rosenman ◽  
Suzanne M. Russo ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Complete Response ◽  
Definitive Treatment ◽  
Thoracic Radiotherapy ◽  
Full Dose ◽  
Kaplan Meier ◽  
Elevated Creatinine

e17547 Background: Weekly paclitaxel-carboplatin or cisplatin-etoposide with C-TRT is the standard of care for unresectable LA-NSCLC, with median survival time (MST) of 16-24 months and 3 year overall survival (OS) of 17-27%. Irinotecan plus platinum with C-TRT has been studied in LA-NSCLC with similar outcomes and no undue toxicities (Langer et al J Thorac Oncol 2007; Bastos et al J Thorac Oncol 2010). We reviewed our multi-disciplinary thoracic oncology program experience of full dose IP with C-TRT in LA-NSCLC. Methods: All patients with unresectable LA-NSCLC treated between January 2007 and December 2011 were searched through our program database and included. 26 patients treated with definitive IP and C-TRT were identified. Treatment consisted of irinotecan 65mg/m2, plus cisplatin 30mg/m2 or carboplatin AUC 3, on days 1 and 8, every 21 days for four cycles. C-TRT started on day 22 at 2 Gy/day for 6-7 weeks. (Total 60-70Gy.) Survival curves were estimated by Kaplan-Meier analysis. Primary end point was OS. Secondary endpoints were overall response rate (ORR), progression free survival (PFS), and toxicities. Results: Patient characteristics: Median age 61 (range 44-82); 73% males; 50% squamous, 31% adenocarcinoma, 19% other histology; 30% Stage IIIA/ 62% IIIB/8% IIB. 1 patient died early without evaluation. ORR was 69%, 5 (19%) complete response, 13 (50%) partial response, 7 (27%) stable disease. Median PFS 10.1 months. MST 31.4 months. One year OS 67.8% (95% CI 52-89) and three year OS 35.7% (95%CI 15-87). 12 (46%) patients had G3/4 hematologic toxicities: 7 neutropenia, 6 thrombocytopenia, 6 anemia, 2 lymphopenia. 9 (34.6%) patients had G3/4 non-hematologic toxicities: 4 radiation esophagitis, 3 elevated creatinine, 2 pneumonia, 2 nausea/vomiting. 1 G5 radiation pneumonitis. Two patients died of pneumonia and sepsis. 18 (69%) patients completed 4 cycles IP with concurrent TRT. Conclusions: Definitive treatment with full dose Irinotecan plus platinum and concurrent thoracic radiotherapy is effective and tolerable for unresectable LA-NSCLC with an enhanced MST of 31 months and 3 year OS of 35%.

Institutional retrospective review of presurgical cisplatin-based chemotherapy (chemo) in patients with urothelial carcinoma (UC): Gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 365-365
Author(s):  
Lauren Christine Harshman ◽  
Susanna J. Jacobus ◽  
Stephanie A. Mullane ◽  
Hope Feldman ◽  
Michelle S. Hirsch ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumor Resection ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Logrank Test ◽  
Exact Test ◽  
Kaplan Meier ◽  
Node Positive Disease ◽  
Muscle Invasive ◽  
Dose Dense

365 Background: Neoadjuvant cisplatin-based chemo is the standard of care for muscle invasive UC. ddMVAC and GC are frequently used regimens but have not been directly compared. The choice is often based on physician preference and toxicity profile. We interrogated a pre-existing database of UC patients (pts) for differences in efficacy and toxicity among them. Methods: From 2007-2013, consecutive pts who had received presurgical chemo prior to primary tumor resection for muscle invasive, non-metastatic UC were identified. Tolerability, toxicity and efficacy were evaluated. Rates were calculated by regimen and compared using Fisher’s exact test. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by regimen using logrank test. Cox regression estimated hazard ratios (HR) in univariate and adjusted models. Results: Of the96 patients eligible for analysis (GC: 40, ddMVAC: 56), 42% of GC pts had ≥cT3 and 23% had cN+ compared to 62% and 39% with ddMVAC. pCR rate was 18% for GC and 27% for ddMVAC (p=0.33). With a median follow-up of 28 mo., 2-yr OS probabilities were 59% [95% CI:(39-74)] on GC and 77%[95%CI:(60-87%)] on ddMVAC (p=0.1). Conclusions: Despite having more clinical ≥T3 and node positive disease at baseline, ddMVAC is at least as active as GC and achieved a numerically higher rate of pCRs/≤pT1 than GC in our cohort. No unexpected toxicities surfaced. Dose delays, discontinuations, and most selected toxicities appeared higher with GC. Neither DFS or OS significantly differed between the two regimens, however, there was a trend to greater benefit with ddMVAC. [Table: see text]

Association of prior pelvic radiation with long-term oncologic outcomes following radical cystectomy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 308-308
Author(s):  
Harras B. Zaid ◽  
Matthew K. Tollefson ◽  
Igor Frank ◽  
William P. Parker ◽  
Robert Houston Thompson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Disease Recurrence ◽  
Oncologic Outcomes ◽  
Rank Test ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Surgical Complexity

308 Background: Receipt of pelvic radiotherapy (PRT) prior to radical cystectomy (RC) has unclear association on oncologic outcomes. Methods: The Mayo Clinic Cystectomy Registry was queried to review 2139 patients undergoing RC for M0 bladder cancer between 1990 and 2010. We then identified patients receiving PRT prior to RC, and matched these cases to non-radiated controls (~1:2) on the basis of age, sex, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Cancer-specific survival (CSS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Of 2139 patients undergoing RC, 104 (4.9%) had received PRT prior to surgery. These patients were matched to 191 non-radiated control patients (no PRT). Overall, patients were well-matched on disease and patient characteristics. Median follow-up was 9.6 years (IQR 6.0, 14.8). During this time, 108 patients experienced disease recurrence and 218 died, including 122 who died from bladder cancer. Five-year CSS among patients who did versus did not receive PRT was 55% versus 63% (p=0.10), while the 5-year PFS was 55% versus 61% (p=0.32). Furthermore, the pattern of disease recurrence (abdominal/visceral, urothelial, local/pelvic, thoracic, soft tissue/other) did not differ between the no PRT and PRT groups (all p>0.05). Conclusions: Receipt of PRT prior to RC is not associated with worse oncologic outcomes. While prior PRT may increase surgical complexity, CSS, PFS, and patterns of recurrence are similar to patients who have not received PRT.

Real-world treatment patterns and clinical outcomes in patients receiving second-line (2L) treatment for advanced or metastatic gastric cancer (GC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 102-102
Author(s):  
Mayur Amonkar ◽  
David Gomez-Ulloa ◽  
Smita Kothari ◽  
Winson Y. Cheung ◽  
Ian Chau ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Outcomes ◽  
Real World ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Metastatic Gastric Cancer ◽  
Treatment Patterns ◽  
Randomised Controlled

102 Background: Despite increased survival demonstrated for patients with advanced / metastatic GC due to 2L chemotherapy, different standard of care options exist. This study aims to describe RW treatment patterns and clinical outcomes in patients with advanced / metastatic GC receiving 2L treatment. Methods: Retrospective chart review study conducted in Australia, Canada, Italy and UK. Patients diagnosed with metastatic / unresectable GC receiving 2L treatment between January 2013 and July 2015 were enrolled. Patient characteristics, treatment patterns and clinical outcomes were captured for 12 months from the start of 2L treatment or until death. Results: 280 patients were included (mean age 60.9 years, 68.9% male). Half of the patients (51.8%) received monotherapy in 2L. Among these, taxanes were most prescribed (69.0%) followed by irinotecan (22.1%). Doublet chemotherapy was the most common combination therapy in 2L (75.6%) with fluoropyrimidine + irinotecan (33.3%) being the most used, followed by fluoropyrimidine + platinum (17.8%). Less than a third of patients (29.3%) received subsequent third-line (3L) treatment; 62.7% received monotherapy [mainly taxanes (69.2%) or irinotecan (19.2%)]. Most 3L patients who had combination therapy received a doublet (86.7%), most frequently fluoropyrimidine combined with irinotecan (53.3%) or platinum (20.0%). The majority of 2L patients (93.6%) had received combination therapy as first-line treatment, of whom 67.9% had received triplet chemotherapy, most commonly anthracycline + fluoropyrimidine + platinum (51.1%). Estimated median real-world progression free survival (PFS) and overall survival (OS) after 2L treatment initiation was 3.09 (95% CI: 2.76-3.68) and 6.54 (5.29-7.76) months, respectively, and estimated probability of PFS and OS at 12 months was 8% and 26%, respectively. Conclusions: The clinical management of advanced / metastatic GC patients in 2L treatment commonly involves taxanes or irinotecan as monotherapy, or irinotecan or platinum-based combinations with fluoropyrimidines. RW clinical outcomes for 2L treatment are similar to randomised controlled trials but remain poor.

scholarly journals Glioblastoma and Increased Survival with Longer Chemotherapy Duration

2019 ◽  
Vol 12 (3) ◽  
pp. 65-69 ◽  
Author(s):  
Dory Abou Jaoude ◽  
Joseph A Moore ◽  
Matthew B Moore ◽  
Philip Twumasi-Ankrah ◽  
Elizabeth Ablah ◽  
...  
Keyword(s):  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Optimal Duration ◽  
Multicenter Prospective Study ◽  
One Year

Introduction The five-year survival rate for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remains the standard of care. The optimal duration of therapy with TMZ is unknown. This study sought to evaluate the survival benefit of two years of treatment. Methods This was a retrospective chart review of all patients diagnosed with GBM and treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) and the overall survival (OS). The results were compared to historical controls and data from previous clinical trials of patients treated up to one year. Results Data from 56 patients with confirmed GBM were evaluated. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years, and 4% (SE = 0.041) at five years. Seven patients (12.5%) were treated with TMZ for two years. Their median time-to-progression was 28 months (95% CI = 5.0 - 28.0), and they had an increased survival probability at three years compared to other patients (log-rank test χ2 (1, N = 56) = 19.2, p < 0.0001). Conclusions There may be an advantage for a longer duration of TMZ therapy among patients with GBM, but the sample size was too small for generalization. A multicenter prospective study is needed to dentify optimal duration of TMZ therapy.

scholarly journals A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial

2021 ◽  
Vol 5 (4) ◽  
pp. 984-993
Author(s):  
Ken Ohmachi ◽  
Tomohiro Kinoshita ◽  
Kensei Tobinai ◽  
Gakuto Ogawa ◽  
Tomonori Mizutani ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Complete Response ◽  
Phase 2 ◽  
Phase 3 ◽  
Free Survival ◽  
Significant Difference ◽  
Dose Dense

Abstract Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.

NOA-04 Randomized Phase III Trial of Sequential Radiochemotherapy of Anaplastic Glioma With Procarbazine, Lomustine, and Vincristine or Temozolomide

2009 ◽  
Vol 27 (35) ◽  
pp. 5874-5880 ◽  
Author(s):  
Wolfgang Wick ◽  
Christian Hartmann ◽  
Corinna Engel ◽  
Mandy Stoffels ◽  
Jörg Felsberg ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Extent Of Resection ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Intention To Treat ◽  
Anaplastic Gliomas ◽  
Mgmt Promoter

Purpose The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas. Patients and Methods Patients (N = 318) were randomly assigned 2:1:1 (A:B1:B2) to receive conventional radiotherapy (arm A); procarbazine, lomustine (CCNU), and vincristine (PCV; arm B1); or temozolomide (arm B2) at diagnosis. At occurrence of unacceptable toxicity or disease progression, patients in arm A were treated with PCV or temozolomide (1:1 random assignment), whereas patients in arms B1 or B2 received radiotherapy. The primary end point was time to treatment failure (TTF), defined as progression after radiotherapy and one chemotherapy in either sequence. Results Patient characteristics in the intention-to-treat population (n = 274) were balanced between arms. All histologic diagnoses were centrally confirmed. Median TTF (hazard ratio [HR] = 1.2; 95% CI, 0.8 to 1.8), progression-free survival (PFS; HR = 1.0; 95% CI, 0.7 to 1.3, and overall survival (HR = 1.2; 95% CI, 0.8 to 1.9) were similar for arms A and B1/B2. Extent of resection was an important prognosticator. Anaplastic oligodendrogliomas and oligoastrocytomas share the same, better prognosis than anaplastic astrocytomas. Hypermethylation of the O6-methylguanine DNA-methyltransferase (MGMT) promoter (HR = 0.59; 95% CI, 0.36 to 1.0), mutations of the isocitrate dehydrogenase (IDH1) gene (HR = 0.48; 95% CI, 0.29 to 0.77), and oligodendroglial histology (HR = 0.33; 95% CI, 0.2 to 0.55) reduced the risk of progression. Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm. Conclusion Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas. IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation.

Eight cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): Final analysis of the HD12 trial of the German Hodgkin Study Group (GHSG)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8544-8544 ◽  
Author(s):  
V. Diehl ◽  
H. Haverkamp ◽  
R. Mueller ◽  
H. Mueller-Hermelink ◽  
T. Cerny ◽  
...  
Keyword(s):  
Residual Disease ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Rank Test ◽  
Advanced Stage ◽  
Data Set ◽  
Who Grade ◽  
Significant Difference

8544 Background: The GHSG HD9 trial had established BEACOPP escalated (BE) as new standard of care for advanced-stage HL patients. The successor study, HD12, evaluated a possible reduction in toxicity by comparing 8 cycles of BE with 4 cycles BE followed by 4 cycles BB. The second question in this trial related to the need of additional radiotherapy (RT) to initial bulk and residual disease. Methods: HL patients in stage IIB with large mediastinal mass and/or E-lesions or stage III/IV were randomised according to a 2x2-factorial design between: 8BE + RT, 8BE no RT, 4BE+4BB + RT, 4BE+4BB no RT. Primary endpoint of the trial was FFTF. Between 9/1999 and 1/2003, a total of 1,670 patients aged 16–65 were randomized. For this final analysis at a median follow up of 78 months, 99 patients were excluded for various reasons resulting in 1,571 eligible patients. Results: Patient characteristics in the 4 groups were comparable. Treatment-related toxicity of WHO grade III/IV was observed in 97% of patients. Most prominent differences between pooled chemotherapy arms were anemia (65% 8BE vs 51% 4BE+4BB) and thrombopenia (65% vs 51%). Treatment outcome: complete remission 92.4%; early progression 2.2%; progression/relapse 7.8% (6.6% and 8.5%). A total of 156 (9.9%) deaths (72 vs 84) have been observed (22 vs 32 acute or salvage treatment toxicity; 15 vs 24 HL; 22 vs 13 secondary neoplasia). Most treatment related deaths occurred in the >60 years age group, the first 4 cycles and the IPS> 3 RF groups. Secondary neoplasias were observed in 77 patients (4.9%). At 5 years, OS was 91%, FFTF 85.5% and progression free survival (PFS) 86.2% (Kaplan-Meier estimates). Estimates for the difference at 5 years are 1.8% for OS, 2.3% for FFTF and 2.7% for PFS favoring BE. However, there was no statistical difference between 8x BE and 4BE+4BB in all outcome parameters (p>0.19, log rank test). There is also no significant difference between the RT or no-RT arms in this study. Conclusions: The adoption of 4BE+4BB as a new standard in the future GHSG studies will depend on a refined analysis of the total data set and will be presented. No significant financial relationships to disclose.

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