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: 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 Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrea DeCensi ◽  
Harriet Johansson ◽  
Thomas Helland ◽  
Matteo Puntoni ◽  
Debora Macis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Low Dose ◽  
Cancer Recurrence ◽  
Phase Iii ◽  
Cyp2d6 Genotype ◽  
Phase Iii Trial ◽  
Reactive Protein ◽  
Non Invasive ◽  
Tamoxifen Metabolites ◽  
Dose Trial

AbstractLow-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3–11.4) in patients who recurred vs 7.5 (5.1–10.2) in those who did not recur (p = 0.60). Tamoxifen and metabolites significantly decreased C-reactive protein (CRP, p < 0.05), and a CRP increase after 3 years was associated with higher risk of recurrence (HR = 4.37, 95% CI, 1.14–16.73, P = 0.03). In conclusion, endoxifen is below 9 nM in most subjects treated with 5 mg/day despite strong efficacy and there is no association with recurrence, suggesting that the reason for tamoxifen failure is not poor drug metabolism. Trial registration: ClinicalTrials.gov, Identifier: NCT01357772.

scholarly journals Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial

2017 ◽  
Vol 78 ◽  
pp. 61-69 ◽  
Author(s):  
Takayuki Yoshino ◽  
Radka Obermannová ◽  
György Bodoky ◽  
Rocio Garcia-Carbonero ◽  
Tudor Ciuleanu ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Carcinoembryonic Antigen ◽  
Predictive Factor ◽  
Phase Iii ◽  
Second Line ◽  
Metastatic Colorectal Carcinoma ◽  
Phase Iii Trial

Biochemical modulation of bolus fluorouracil by PALA in patients with advanced colorectal cancer.

1992 ◽  
Vol 10 (5) ◽  
pp. 747-752 ◽  
Author(s):  
N Kemeny ◽  
J A Conti ◽  
K Seiter ◽  
D Niedzwiecki ◽  
J Botet ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Median Survival ◽  
Low Dose ◽  
Complete Response ◽  
Albumin Level ◽  
Phase Iii ◽  
Biochemical Modulation ◽  
Hematologic Toxicity ◽  
Synthesis Inhibitor ◽  
Pyrimidine Synthesis

PURPOSE N-(phosphonacetyl)-L-aspartic acid (PALA) is a pyrimidine synthesis inhibitor that modulates fluorouracil (FU) cytotoxicity. Two previous studies of patients with colorectal carcinoma documented complete response (CR) and partial response (PR) rates of 40% and 43% using weekly low-dose PALA followed by a 24-hour FU infusion. We investigated whether comparable results could be obtained with biochemical modulation by low-dose PALA using bolus instead of infusional FU. PATIENTS AND METHODS Forty-five patients without prior chemotherapy who had advanced colorectal carcinoma were treated with PALA 250 mg/m2 followed 24 hours later by bolus FU at three dose levels, 600, 700, 800 mg/m2, repeated weekly for 6 weeks followed by a 2-week break. RESULTS The CR and PR rate was 15 of 43 patients or 35% (95% confidence interval [CI], 21% to 49%), with an overall median survival of 18 months. Grade 3 or 4 diarrhea was the major toxicity observed in 24% of patients receiving FU at 700 mg/m2 and in 43% of patients receiving 800 mg/m2. Hematologic toxicity was observed only with an FU dose of 800 mg/m2, and 29% (four of 14) of patients developed grade 4 leukopenia. We also noted the development of ascites in six patients, mild hyperbilirubinemia in 16 patients, and a decreased albumin level in 22 patients; these abnormalities occurred more frequently in responding patients. CONCLUSIONS The observed response rate, median survival, and toxicity in this study are similar to those obtained with PALA plus infusional FU and with other methods of FU modulation. Larger phase III studies are needed to compare bolus FU/PALA regimens with other PALA and non-PALA-containing combinations. Our future focus will be attenuate this regimen's toxicity while maintaining or improving its response rates and survival.

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