Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this study was to ascertain the first cycle intolerability rate of the standard Mayo Clinic regimen, 5-fluorouracil (5-FU) 425 mg/m2 with low-dose folinic acid (FA) 20 mg/m2, as a rapid bolus intravenous injection (5-FU/FA) for 5 days every 4-5 weeks for advanced colorectal cancer chemotherapy. The 5-FU/FA arms of 2 large, randomized, controlled trials of 5-FU/FA versus raltitrexed, performed in Europe and North America, were analyzed for intolerability. Two hundred and twelve European patients and 200 North American patients with locally advanced or distant metastatic colorectal cancer were assigned to the Mayo Clinic regimen. During cycle 1, intolerability of the therapy was assessed. Intolerability was recognized as a protocol-driven, toxicity-mandated dose reduction in cycle 2, the inability to complete 5 days of cycle 1 due to toxicity, or failure to receive cycle 2 at all because of toxicity. After the first cycle of chemotherapy, the intolerability rate for the European trial was 41.0% (95% confidence interval [CI], 34.3-47.6) and 49.0% (95% CI, 42.0-56.0) for the North American trial. For the combined 5-FU/FA populations, the intolerability rate was 44.8% (95% CI, 40.0-49.7). The predominant toxicities were stomatitis, diarrhea, and leukopenia. The standard Mayo Clinic regimen was associated with a higher level of dose-limiting toxicities than the accepted maximum of up to 33% for standard chemotherapy.
Clin Colorectal Cancer 2002 Aug
PMID:Toxicity analysis of the 5-day bolus 5-fluorouracil/folinic acid regimen for the treatment of colorectal carcinoma from 2 randomized controlled trials: a concern about dose. 1245 26

Attempts at improving the efficacy of 5-fluorouracil (5-FU) by protracted continuous infusion and/or biochemical modulation have been hindered by the need for indwelling central venous catheters and their associated toxicity. Capecitabine, an oral fluoropyrimidine carbamate, has been rationally synthesized as an inactive precursor that is absorbed intact through the intestinal mucosa and is sequentially converted by an enzymatic cascade involving 3 distinct enzymes to 5'-deoxy-5-fluorocytidine, to 5'-deoxy-5-fluorouridine (5'-DFUR), and finally to 5-FU. Preclinical studies provided evidence of preferential intratumoral conversion of inactive 5'-DFUR to active 5-FU due to the relative overexpression of the final anabolizing enzyme, thymidine phosphorylase, in tumor tissues, with a resultant decrease of 5-FU exposure in normal tissues. The safety of capecitabine and optimal dosing schedules have been explored in phase I/II studies, resulting in the evaluation of the intermittent schedule (1250 mg/m2 twice daily for 14 days, every 3 weeks) in most subsequent clinical trials. Two large randomized phase III studies in patients with metastatic colon cancer established at least equivalent efficacy and improved tolerability with capecitabine compared to the Mayo Clinic bolus 5-FU/leucovorin regimen. The most common treatment-related adverse events are palmar-plantar erythrodysesthesia, diarrhea, and stomatitis, with grade 3/4 events occurring in 17%, 15%, and 2%-8% of patients, respectively. Myelosuppression was minimal. Overall toxicity was easily managed, with a significant reduction in the frequency of hospitalizations and medical resource use. The spectrum of clinical efficacy of capecitabine is expected to encompass other tumor types and administration in the adjuvant setting. As a home-based outpatient regimen, capecitabine represents a safe and effective advance in modern drug development.
Clin Colorectal Cancer 2002 May
PMID:Capecitabine (Xeloda): from the laboratory to the patient's home. 1245 32

Coadministration of eniluracil with 5-fluorouracil (5-FU) allows the oral absorption of small doses of 5-FU, resulting in therapeutic plasma levels. A phase II clinical trial of this combination using a continuous dosing schedule was carried out in patients with metastatic colorectal cancer. Fifty-three previously untreated patients and 46 patients who had received one prior regimen for metastatic disease were enrolled. Patients received 10 mg/m2 of eniluracil and 1 mg/m2 of 5-FU twice daily for 28 days, with cycles repeated after a 7-day rest until progression of disease or prohibitive toxicity. Seven of 53 previously untreated patients had an objective tumor response (13.2%): 1 complete response and 6 partial responses. The mean duration of response was 6.3 months. Only 1 of the 45 evaluable patients in the previously treated group had a partial response, with no complete responses. The duration of response was 3 months. The median progression-free survival was 3.4 months for the previously untreated group and 2.5 months for the previously treated group. Median overall survival was 11.1 months for the previously untreated group and 9.0 months for the previously treated group. Hematologic toxicity was infrequent, with 3 patients experiencing grade 3 toxicity. Incidence of grade 3/4 toxicity included 11 patients with diarrhea, 5 with nausea, and 4 with vomiting. Other common toxicities included anemia and stomatitis, but they were generally mild. This regimen is well tolerated and shows activity in previously untreated patients with metastatic colorectal cancer that is similar to that observed with other 5-FU-based regimens. This regimen has not shown to be effective in patients who have had prior chemotherapy.
Clin Colorectal Cancer 2002 May
PMID:Eastern Cooperative Oncology Group phase II trial (E4296) of oral 5-fluorouracil and eniluracil as a 28-day regimen in metastatic colorectal cancer. 1245 37

Although 5-fluorouracil (5-FU)-based chemotherapy is commonly used in patients with advanced colorectal cancer (CRC), little data exist on the tolerability and benefit of therapy in elderly patients. To compare toxicity, dose intensity, response rate, time to tumor progression, and overall survival for older and younger patients, we conducted a pooled analysis of 1748 patients, divided into 4 quartile-based age groups, from 4 North Central Cancer Treatment Group trials testing 5-FU with or without leucovorin for advanced CRC. Patients aged > 65 years had modestly higher rates of severe toxicity (grade >/= 3) overall (53% vs. 46%) and higher rates of diarrhea (21% vs. 16%), stomatitis (17% vs. 13%), and infection (4% vs. 2%). Toxicity rates were similar between patients aged 66-70 years and patients aged > 70 years. The response rate did not differ by age group (2-sided; P = 0.90); it was significantly lower for patients with higher performance status scores (30% for score of 0/1; 17% for 2/3; 2-sided; P = 0.001). Performance status, not age, was predictive of time to tumor progression and overall survival. The older patients with CRC treated with 5-FU have modestly higher rates of severe toxicity, mainly diarrhea and stomatitis. Supportive measures to control diarrhea and stomatitis may be particularly important in elderly patients. Age alone should not be used to determine whether older patients are treated, because performance status is predictive of dose intensity, response rate, time to tumor progression, and overall survival.
Clin Colorectal Cancer 2005 Jan
PMID:5-Fluorouracil-based chemotherapy for advanced colorectal cancer in elderly patients: a north central cancer treatment group study. 1566 36

Colorectal cancer continues to pose a major public health threat in the United States. Without postsurgical adjuvant therapy, approximately 50% of patients will have recurrent disease and die within five years. Since 1990, five new chemotherapy agents have been added to the therapeutic armamentarium for management of colorectal cancer, and agents traditionally used to treat metastatic and advanced disease increasingly are being applied in the adjuvant setting. One such treatment, capecitabine, offers patients the benefit of oral dosing and permits at-home self-management. A phase III randomized trial, Xeloda in Adjuvant Colorectal Cancer Treatment, demonstrated that treatment with single-agent capecitabine was equivalent to bolus 5-fluorouracil with leucovorin with respect to disease-free survival and overall survival, with significantly less diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia. This article reviews the findings and discusses how oncology nurses can help provide effective education and monitoring for patients using oral treatment in the adjuvant setting.
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PMID:Capecitabine: a new adjuvant option for colorectal cancer. 1692 1

5-Fluorouracil (5-FU) is an antimetabolite that acts during the S phase of the cell cycle. The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase (TS), thus preventing DNA synthesis, which leads to imbalanced cell growth and ultimately cell death. 5-FU and its oral prodrug capecitabine are used in the treatment of a number of solid tumors, including colorectal, breast, gastric, pancreatic, prostate, and bladder cancers. Common side effects include leukopenia, diarrhea, stomatitis, nausea, vomiting, and alopecia. Hand-foot syndrome (HFS) is a relatively common side effect of cytotoxic chemotherapy. It is more frequently associated with 5-FU, capecitabine, and cytarabine. This article reports on the case of a 55-year-old black man with metastatic colorectal carcinoma that was refractory to recommended treatment measures who developed grade 3 HFS after treatment with modified FOLFOX6 (leucovorin [LV]/5-FU/oxaliplatin) and bFOL (bolus 5-FU/LV/oxaliplatin) regimens. Treatment was discontinued despite excellent response to chemotherapy. The patient had progression of disease on IROX (irinotecan/oxaliplatin) and irinotecan/cetuximab regimens. He was started on gemcitabine/capecitabine and developed HFS again, which was controlled with aggressive skin care and vitamin B6 treatment. Full sequencing of the dihydropyrimidine dehydrogenase (DPYD) gene and analysis of the human TS gene (TYMS) promoter region was performed. Pharmacogenetic testing revealed 2R/2R genotype of TYMS gene, which is associated with up to a 2.5-fold risk of toxicity to 5-FU therapy. Hand-foot syndrome has proven to be a dose-limiting toxicity of 5-FU, especially of capecitabine, leading to significant morbidity. Hand-foot syndrome seems to be dose dependent, and both peak drug concentration and total cumulative dose determine its occurrence. Genetic variations such as polymorphic abnormality of TYMS are potential causative factors for a significant portion of serious adverse reactions to 5-FU-based therapy.
Clin Colorectal Cancer 2009 Oct
PMID:Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: A challenge or a dilemma? 1982 15