Enhancing the efficacy of single-agent fluorouracil in colorectal cancer?

InPharma ◽  
1989 ◽  
Vol 716 (1) ◽  
pp. 10-10
Keyword(s):  
Colorectal Cancer ◽  
Single Agent

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer

2002 ◽  
Vol 50 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Ychou M. ◽  
Raoul J. ◽  
Desseigne F. ◽  
Borel C. ◽  
Caroli-Bosc F. ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

1998 ◽  
Vol 16 (10) ◽  
pp. 3461-3475 ◽  
Author(s):  
A Sulkes ◽  
S E Benner ◽  
R M Canetta
Keyword(s):  
Colorectal Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Response Rates ◽  
The United States ◽  
Maximum Tolerated Dose ◽  
Oral Route ◽  
Western World ◽  
Oral Fluoropyrimidine ◽  
Hand Foot Syndrome

PURPOSE AND DESIGN This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. RESULTS Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. CONCLUSION UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

scholarly journals First-line single-agent panitumumab in frail elderly patients with wild-type RAS unresectable colorectal cancer: a phase II study protocol OGSG 1602

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tetsuji Terazawa ◽  
Takeshi Kato ◽  
Masahiro Goto ◽  
Daisuke Sakai ◽  
Yukinori Kurokawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Phase Ii ◽  
Study Protocol ◽  
Frail Elderly ◽  
Phase Ii Study ◽  
Single Agent ◽  
Wild Type ◽  
First Line

Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1337-1345 ◽  
Author(s):  
Eric Van Cutsem ◽  
Michael Findlay ◽  
Bruno Osterwalder ◽  
Walter Kocha ◽  
David Dalley ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Dose Intensity ◽  
Patient Characteristics ◽  
Complete Response ◽  
Phase Iii ◽  
Effective Treatment Option ◽  
Randomized Phase Ii

PURPOSE: To evaluate in patients with advanced colorectal cancer (CRC) three treatment regimens of oral capecitabine in order to select the most appropriate regimen for testing in phase III. PATIENTS AND METHODS: Three capecitabine schedules were evaluated in a randomized phase II design: arm A, 1,331 mg/m2/d bid continuously; arm B, 2,510 mg/m2/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 mg/m2/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). RESULTS: One hundred nine patients were randomized; 39 patients were assessable for efficacy in arm A, 34 in arm B, and 35 in arm C. Patient characteristics were balanced in the arms. Confirmed tumor responses (partial response [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patients with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with two CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, more toxicity was seen with capecitabine plus leucovorin, particularly diarrhea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity. CONCLUSION: Capecitabine offers a new, effective treatment option as an oral single agent in advanced CRC. Promising overall response rates were reported for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermittent single-agent capecitabine schedule is proposed for phase III evaluation, based on considerations of toxicity, dose-intensity, response rate, and TTP.

scholarly journals Sourcing the immune system to induce immunogenic cell death in Kras-colorectal cancer cells

2019 ◽  
Vol 121 (9) ◽  
pp. 768-775
Author(s):  
Mara Cirone ◽  
Lavinia Vittoria Lotti ◽  
Marisa Granato ◽  
Livia Di Renzo ◽  
Ida Biunno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Single Agent ◽  
Atp Release ◽  
Immunogenic Cell Death ◽  
Dendritic Cell Activation ◽  
Colorectal Cancer Cells

Abstract Background Current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents. Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations. Methods Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts. Results We report that an ICD process can be activated without the use of pharmacological compounds. We show that in Kras-mut/TP53-mut colorectal cancer cells the 15 kDa βGBP cytokine, a T cell effector with onco-suppressor properties and a potential role in cancer immunosurveillance, induces key canonical events required for ICD induction. We document ER stress, autophagy that extends from cancer cells to the corresponding xenograft tumours, CRT cell surface shifting, ATP release and evidence of dendritic cell activation, a process required for priming cytotoxic T cells into a specific anticancer immunogenic response. Conclusions Our findings provide experimental evidence for a rationale to explore a strategy based on the use of an immunomolecule that as a single agent couples oncosuppression with the activation of procedures necessary for the induction of long term response to cancer.

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