Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma

2 Background: AOD are chemotherapy-sensitive tumors especially if 1p/19q co-deleted. Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine chemotherapy (PCV) in AOD. We now present long-term follow-up. Methods: Patients (pts) with locally diagnosed newly diagnosed AOD were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles of standard PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression-free survival (PFS). 1p/19q status, IDH status and MGMT promoter methylation were determined in 300, 167, and 186 pts respectively. Results: Between 1996 and 2002, 368 pts were included. At the time of analysis 281 pts (76.4%) had died. Median PFS after RT/PCV was significantly longer compared to RT alone (24.3 months versus 13.21 months, hazard ratio [HR] 0.66, [95% confidence interval (95% CI) 0.52, 0.83]). More RT arm patients received chemotherapy at progression (75% vs 53%). Median OS was also significantly prolonged in the RT/PCV arm (42.3 months vs 30.6 months for the RT arm, HR 0.75 [95% CI 0.60, 0.95]). 1p/19q co-deleted patients (n = 76) treated with RT/PCV had improved OS compared to RT arm pts (median OS not reached vs 113 months; HR 0.54, p = 0.0487). In the 224 patients without 1p/19q co-deletion the difference in OS was non-significant (OS RT/PCV arm 25 months vs 22 months in the RT arm, HR 0.82, p = 0.18; test for interaction p = 0.22). There was a slight trend towards improved OS in MGMT methylated and IDH mutated tumors versus unmethylated and IDH wild type tumors (Table). Conclusions: The addition of PCV to RT increases PFS and OS in AOD. Pts with 1p/19q co-deletion appear to benefit most from the addition of PCV, with a trend for improved OS in pts with MGMT methylation and IDH mutations. [Table: see text]

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Long-term follow-up results of EORTC 26951: A randomized phase III study on adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (AOD).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2-2

Author(s):

Martin J. Van Den Bent ◽

Khê Hoang-Xuan ◽

Alba Ariela Brandes ◽

Johan M Kros ◽

Mathilde C.M. Kouwenhoven ◽

...

Keyword(s):

Annual Meeting ◽

Phase Iii ◽

Daily News ◽

Online Supplement ◽

Oligodendroglial Tumors ◽

Long Term Follow Up ◽

Phase Iii Study ◽

Final Text

2 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

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A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6032 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6032-6032

Author(s):

Wang Fang FangZheng

Keyword(s):

Clinical Trial ◽

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Phase Iii ◽

Karnofsky Performance Score ◽

Long Term Outcomes ◽

First Line ◽

Grade 3

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.

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Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.7.2564 ◽

1997 ◽

Vol 15 (7) ◽

pp. 2564-2569 ◽

Cited By ~ 374

Author(s):

S B Saxman ◽

K J Propert ◽

L H Einhorn ◽

E D Crawford ◽

I Tannock ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Combination Chemotherapy ◽

Performance Status ◽

Single Agent ◽

Phase Iii ◽

Long Term Follow Up ◽

Intergroup Trial ◽

Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

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Abstract GS3-06: Long-term follow-up of CALGB 40502/NCCTG N063H (Alliance): A randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-Paclitaxel (NP) or ixabepilone (Ix) +/- bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer (MBC)

10.1158/1538-7445.sabcs17-gs3-06 ◽

2018 ◽

Cited By ~ 2

Author(s):

HS Rugo ◽

WT Barry ◽

A Moreno-Aspitia ◽

A Lyss ◽

L Huebner ◽

...

Keyword(s):

Metastatic Breast ◽

Phase Iii ◽

First Line ◽

Phase Iii Trial ◽

First Line Therapy ◽

Line Therapy ◽

Long Term Follow Up ◽

Locally Recurrent

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T1 Top Line Results of the DETECT Enzymatic Debridement Multicenter Randomized Controlled Trial

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa024.000 ◽

2020 ◽

Vol 41 (Supplement_1) ◽

pp. S1-S1

Author(s):

William L Hickerson ◽

Jeremy Goverman ◽

Sigrid A Blome-Eberwein ◽

Adam Singer ◽

Lucy Wibbenmeyer

Keyword(s):

Median Time ◽

Wound Closure ◽

The United States ◽

Acute Stage ◽

Phase Iii ◽

Randomized Controlled ◽

Multicenter Randomized Controlled Trial ◽

Long Term Follow Up

Abstract Introduction Bromelain Based Debridement (BBD) of deep burns is approved for use in Europe, Argentina, Russia, South Korea, Peru and Israel. In the United States it is an investigational product and currently there are 2 multicenter RCTs (DETECT – adults, CIDS – children). Patient enrollment in the DETECT adult trial has been completed. The aim of this abstract is to present the acute stage top line results of the DETECT trial. Methods 175 adult patients suffering from deep burns were included in a phase III multicenter, multinational, randomized, controlled, assessor blinded trial. Patients were randomized to 3 arms – BBD, Standard of Care (SOC), or Gel vehicle (Placebo control) in a 3:3:1 ratio (75 BBD, 75 SOC, 25 Gel). The primary endpoint was the incidence of complete eschar removal (BBD vs Gel). Additional acute stage endpoints included the time to complete eschar removal, incidence of surgical eschar removal and eschar removal associated blood loss.Time to complete wound closure (BBD vs SOC) was assessed as a safety endpoint. Following the acute stage, a long-term follow up period of 2 years is being conducted. Results Patient demographics and wound baseline characteristics were comparable across study arms.The incidence of complete eschar removal was significantly higher for BBD vs Gel patients (93.3% vs 4%, p< 0.0001). The incidence of surgical eschar removal was significantly lower for BBD vs SOC patients (4% vs 72%, p< 0.0001). The median time to complete eschar removal was significantly shorter for BBD vs SOC patients (1 day vs 3.8 days, p< 0.0001). Calculated eschar removal associated blood loss was significantly lower for BBD vs SOC patients (14ml vs 815ml, p< 0.0001). The median time to complete wound closure was similar for BBD and SOC patients (27 and 28 days). The overall safety profile of BBD treated patients was good and consistent with the safety data known from previous studies.The results of the long term follow up period are not yet available. Conclusions The acute stage results of this robust phase III RCT demonstrate the safety and efficacy of BBD and are in line with previous trial results. Applicability of Research to Practice The results of this trial may help pave the way for US approval of BBD.

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Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.5083 ◽

2018 ◽

Vol 36 (7) ◽

pp. 697-703 ◽

Cited By ~ 24

Author(s):

Mazyar Shadman ◽

Hongli Li ◽

Lisa Rimsza ◽

John P. Leonard ◽

Mark S. Kaminski ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Randomized Study ◽

Phase Iii ◽

Second Malignancies ◽

Long Term Follow Up ◽

Acute Myeloid

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133–tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.

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