The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.

1989 ◽  
Vol 7 (10) ◽  
pp. 1419-1426 ◽  
Author(s):  
N Petrelli ◽  
H O Douglass ◽  
L Herrera ◽  
D Russell ◽  
D M Stablein ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Low Dose ◽  
Phase Iii ◽  
High Dose ◽  
Metastatic Colorectal Carcinoma ◽  
Phase Iii Trial ◽  
Severe Diarrhea ◽  
Gastrointestinal Tumor Study Group ◽  
The Impact ◽  
Dose Limiting Toxicity

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.

scholarly journals The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced colorectal carcinoma: Results of a phase III trial

1998 ◽  
Vol 9 (5) ◽  
pp. 535-541 ◽  
Author(s):  
M.M. Borner ◽  
M. Castiglione ◽  
M. Bacchi ◽  
W. Weber ◽  
R. Herrmann ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Low Dose ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Advanced Colorectal Carcinoma ◽  
The Impact

The Modulation of Fluorouracil With Leucovorin in Metastatic Colorectal Carcinoma

1990 ◽  
Vol 8 (1) ◽  
pp. 185-185 ◽  
Author(s):  
Nicholas Petrelli ◽  
Harold O. Douglass ◽  
Lemuel Herrera ◽  
David Russell ◽  
Donald M. Stablein ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Clin Oncol ◽  
Phase Iii ◽  
Study Group ◽  
Gastrointestinal Tumor ◽  
Metastatic Colorectal Carcinoma ◽  
Phase Iii Trial ◽  
Tumor Study ◽  
Gastrointestinal Tumor Study Group ◽  
Tumor Study Group

The authorship of the report "The Modulation of Fluorouracil With Leucovorin in Metastatic Colorectal Carcinoma: A Randomized Phase III Trial," published in the October 1989 issue (J Clin Oncol 7:1419–1426, 1989) should have read: "by the Gastrointestinal Tumor Study Group." The following appendix should also have appeared at the end of the report:

Phase III Trial of Cisplatin Plus Gemcitabine With Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer: AVAiL

2009 ◽  
Vol 27 (8) ◽  
pp. 1227-1234 ◽  
Author(s):  
Martin Reck ◽  
Joachim von Pawel ◽  
Petr Zatloukal ◽  
Rodryg Ramlau ◽  
Vera Gorbounova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dose Group ◽  
Low Dose ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
High Dose ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Grade 3

Purpose Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non–small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting. Patients and Methods Patients were randomly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m2 for up to six cycles plus low-dose bevacizumab (7.5 mg/kg), high-dose bevacizumab (15 mg/kg), or placebo every 3 weeks until disease progression. The trial was not powered to compare the two doses directly. The primary end point was amended from overall survival (OS) to progression-free survival (PFS). Between February 2005 and August 2006, 1,043 patients were randomly assigned (placebo, n = 347; low dose, n = 345; high dose, n = 351). Results PFS was significantly prolonged; the hazard ratios for PFS were 0.75 (median PFS, 6.7 v 6.1 months for placebo; P = .003) in the low-dose group and 0.82 (median PFS, 6.5 v 6.1 months for placebo; P = .03) in the high-dose group compared with placebo. Objective response rates were 20.1%, 34.1%, and 30.4% for placebo, low-dose bevacizumab, and high-dose bevacizumab plus CG, respectively. Duration of follow-up was not sufficient for OS analysis. Incidence of grade 3 or greater adverse events was similar across arms. Grade ≥ 3 pulmonary hemorrhage rates were ≤ 1.5% for all arms despite 9% of patients receiving therapeutic anticoagulation. Conclusion Combining bevacizumab (7.5 or 15 mg/kg) with CG significantly improved PFS and objective response rate. Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC.

Subcutaneous low-dose interleukin-2 and intravenous 5-fluorouracil plus high-dose levofolinic acid as salvage treatment for metastatic colorectal carcinoma

1996 ◽  
Vol 7 (4) ◽  
pp. 386-391 ◽  
Author(s):  
Vittorio Gebbia ◽  
Antonio Testa ◽  
Evaristo Majello ◽  
Giuseppe Cannata ◽  
Maria Lina Tirrito ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Low Dose ◽  
Interleukin 2 ◽  
Salvage Treatment ◽  
High Dose ◽  
Metastatic Colorectal Carcinoma

Effect of Venous Thrombotic Events on Overall Survival in Multiple Myeloma: Analysis of Thrombotic Events Occurring in E4A03A Randomized Trial of Lenalidomide Plus High-Dose Dexamethasone (RD) Versus Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma, a Trial Coordinated by the Eastern Cooperative Oncology Group (ECOG).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1740-1740 ◽  
Author(s):  
Susanna Jacobus ◽  
Shaji Kumar ◽  
Natalie Scott Callander ◽  
Rafat Abonour ◽  
Rafael Fonseca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Low Dose ◽  
Standard Dose ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
The Impact

Abstract Background: Venous thrombotic events (VTE) are a common complication of therapy with the lenalidomide plus dexamethasone regimen. The incidence of VTE with RD is approximately 20%, and can be lowered with the use of effective thromboprophylaxis, avoidance of erythropoietin, and the use of lower doses of dexamethasone. The goal of this study was to determine the impact of VTE on overall survival of patients with newly diagnosed myeloma by studying events occurring in ECOG E4A03 phase III trial of lenalidomide plus high (standard) dose dex (RD) versus lenalidomide plus low dose dex (Rd) in newly diagnosed myeloma (MM). Methods: Pts with untreated, symptomatic MM were eligible. Pts in the RD arm (Arm A) received lenalidomide 25 mg/day PO days 1–21 every 28 days plus dex 40 mg days 1–4, 9–12, and 17–20 PO every 28 days; pts in the Rd arm (Arm B) received lenalidomide at the same dose plus dex 40 mg days 1, 8, 15, and 22 PO every 28 days. The trial initially did not mandate routine thromboprophylaxis, but recommended that such treatment be considered. After the first 264 patients were enrolled the trial was amended to require mandatory thromboprophylaxis of aspirin for all patients, with a recommendation to use stronger thromboprophylaxis with either warfarin (target INR 2–3) or low molecular weight heparin among patients in the RD arm. Results: 445 pts (median age, 65 yrs) were accrued; 223 randomized to RD, 222 to Rd. Median follow-up time is 30 months. Overall VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 18.5% of patients; 25.6% in Arm A and 11.4% in Arm B. Rates for the first 4 cycles of treatment were 20.2% in Arm A and 8.2% in Arm B, P<0.01. Rates did not change substantially before and after the prophylaxis amendment. A partial response (PR) or higher was seen in 82.1% of pts who experienced VTE compared with 74.6% of pts who did not experience VTE, P=0.19. Overall VGPR rates also were not inferior. Pts who had VTE, however, had significantly higher other grade 3–5 toxicities such as hyperglycemia (14.6% vs 7.5%, P=0.051), cardiac ischemia (4.9% vs 0.8%, P=0.002), non-neuropathic weakness (13.4% vs 6.4%, P=0.039), infection/pneumonia (17.1% vs 11.1%, P=0.138) and fatigue (18.3% vs 10.5%, P=0.060). In a Cox PH model, VTE status as a time-varying covariate was marginally significant: HR 1.54 95%CI (0.96–2.47), P=0.074, suggesting patients that develop VTE have a higher hazard of death. Conclusions: The occurrence of VTE may adversely affect the survival of patients with newly diagnosed myeloma receiving Rev-Dex. VTE was associated with a higher frequency of other serious adverse events. Prevention of VTE events is a priority. Besides lowering the dose of dexamethasone, studies investigating optimum thromboprophylaxis are needed.

Sign in / Sign up

Export Citation Format

Share Document