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)

Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase I trial was designed to determine the maximum tolerated dose, the dose-limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v. infusion for 1 h every 21 days with a starting dose of 150 mg/m2 and an escalation to 185 mg/m2 and 235 mg/m2 in subsequent patient cohorts. G-CSF (5 microg/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the post-nadir neutrophil count reached 10,000/microl. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m2. Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/1microl) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/microl), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis, back pain, asthenia, and neuropathy. One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G-CSF support in children is 185 mg/m2, which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85 % higher than the recommended adult dose.
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PMID:Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial. 1021 6

Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen. Raltitrexed was administered at a dose of 3.0 mg/m2 i.v. over 15 min once every 3 weeks. Of 43 eligible patients, 53% had colon cancer and 47% rectal cancer. Objective responses were observed in 16% of patients [95% confidence interval (CI): 7-31%; seven partial responses). The median duration of response was 101 days (range: 45-239 days), the median overall duration of response was 145 days (range: 104-302 days) and the median survival was 11.6 months (95% CI: 9.4-14.7 months). Liver metastases showed a 17% (three of 18) response rate and lung metastases a 12% (three of 25) response rate. Adverse events of grade 3 or 4 reported for more than 5% of patients were neutropenia (23%), leukopenia (9%), reversible SGPT increase (7%) nausea/vomiting (19%), anorexia (14%), asthenia (9%) and hypotension (7%). Grade 3 or 4 diarrhea, stomatitis and alopecia were not observed. In summary, raltitrexed had an acceptable toxicity profile and promising anti-tumor activity against advanced CRC in patients who had received prior chemotherapy. Further clinical trials of combination chemotherapy using raltitrexed are warranted.
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PMID:Phase II study of raltitrexed (Tomudex) in chemotherapy-pretreated patients with advanced colorectal cancer. Tomudex Cooperative Study Group. 1057 7

The National Institutes of Health (NIH) held a consensus conference which recommended 5-FU and levamisole as adjuvant chemotherapy for colon cancer MAC (Modified Astler Coller) stage C. From 1991-1994, 37 such patients diagnosed here were treated with 5-FU (intravenous dose of 450/mg/m2/d for 5 days and from day 29, once a week for 48 weeks) and oral levamisole (50 mg 3 times/d. for 3 days, every 2 weeks for a year), as suggested by NIH guidelines. 16 patients were males and 21 were females, mean age was 62 years and median 64. Cancer locations were: right colon (in 16, 43%), left colon (19, 51%), multiple colon primaries (2, 1%). 25 (68%) had 1-3 positive lymph nodes and 12 (32%) had 4 or more positive lymph nodes. Only 20 (54%) finished treatment as prescribed. In the others, 1 or both drugs caused side-effects for which the drugs had to be stopped. 6 patients relapsed while on treatment. The most common side-effects were diarrhea, stomatitis and bone marrow suppression. 3 were hospitalized due to neutropenic fever. 5-year actuarial survival of all patients was 61%; 5-year relapse-free survival was 61%; 5-year relapse-free survival of right versus left colon was 41% and 82%, respectively (p < 0.01). There was no significant difference in 5-year survival of those with 1-3 positive lymph nodes as compared to those with 4 or more (62% and 56%, respectively). 5-year survival in those who finished or did not finish treatment (excluding those who stopped treatment because of progressive disease) was 83% and 70%, respectively (NS). The 5-year survival of our series was similar to that of patients treated similarly elsewhere. The 5-FU and levamisole treatment was not tolerated well by our study population. It has recently been replaced in our service by a 5-FU and leucovorin regimen given for 6 months.
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PMID:[Adjuvant therapy of colon cancer stage C MAC. Adverse effects and efficacy in the Department of Oncology, Soroka Medical Center in the years 1991-1994]. 1095 48

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.
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PMID:Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial. 1103 19

We describe in this paper a therapeutic modality which is based on a self-rescuing concept (SRC) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent, tegafur (FT); a DPD inhibitor (CDHP: 5-chloro-2, 4-dihydroxypyridine) which is about 200-fold more potent than uracil used in UFT; and an ORTC inhibitor (Oxo: potassium oxonate) which is localized in the gastrointestinal tract. We devised a novel oral anticancer agent, S-1, as a combination drug with a molar ratio of 1:0.4:1 for FT, CDHP, and Oxo, respectively. To compare S-1, FT, and UFT in terms of their anticancer activity and adverse reactions, a colon cancer implantation model in rats was used for 4-week consecutive oral administration from the time when the postimplantation tumor weight become about 2 g. The tumor disappeared on day 16 at a given dose of S-1 (as 22.5 mg/kg FT), and the tumor did not reappear for at least three months. Antitumor activity was more marked with S-1 than FT and UFT. Adverse reaction, i.e., stomatitis, depilation, and weight loss, were less frequent in the S-1 group than in the other groups. A clinical pharmacology study examined blood concentrations of 5-FU after twice-a-day administration after meals of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were 60 to 200 ng/ml in all twelve patients examined. Late phase II clinical trials of S-1 were conducted in patients with advanced and recurrent stomach cancers, in the same regimen as for the clinical pharmacology study. It basically consisted in four cycles, each of which comprised 4-week, twice-a-day, consecutive oral administration with a 2-week withdrawal. The overall response rate was 44.6% (45/101). Median survival time (MST) was 224 days. S-1 was given manufacturing approval by the Ministry of Health and Welfare of Japan after a priority review, with indications for advanced and recurrent stomach cancers. A late phase II clinical study of S-1 in patients with advanced/recurrent head and neck cancer was conducted in 59 eligible patients. Objective responses were 4 complete response (CR) and 13 partial response (PR), for a response rate of 28.8% (17/59). MST was 344 days. Grade 4 hemoglobin decrease was observed in one case; however, this returned to normal after the termination of drug administration and blood transfusion. Therefore, this event was confirmed to be reversible. A late phase II clinical trial of S-1 was conducted to evaluate the efficacy and toxicities in patients with metastatic colorectal carcinoma. Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled in this clinical trial. The overall response rate was 35.5% (22/62), and the MST was 378 days. The main adverse reactions were myelosuppression and GI toxicities. The incidence of neutropenia (Grade 3 or 4) was 13%, while the incidence of other adverse reactions was 10% or below. None of 53 outpatients required to be hospitalization due to adverse reactions. Late phase II clinical trials of S-1 are in progress for colorectal cancer, breast cancer and non-small cell lung cancer. To establish the standard therapeutic modality for cancers, including gastrointestinal cancers, in Japan, the conduction of clinical trials combining S-1 and other anticancer drugs holds promise for the future.
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PMID:[New oral anticancer drug, TS-1 (S-1)--from bench to clinic]. 1143 58

The purpose of this report is to summarize information on oxaliplatin, a drug recently approved by the U.S. Food and Drug Administration. Information provided includes regulatory history, study design, efficacy and safety results, and pertinent literature references. A single, multicenter, randomized trial, enrolling 463 patients with metastatic colorectal carcinoma whose disease had recurred or progressed during or within 6 months of completion of therapy with the combination of bolus 5-fluorouracil (FU)/leucovorin (LV) and irinotecan, was submitted. Study arms included infusional 5-FU/LV alone (arm A), oxaliplatin alone (arm B), and the combination of oxaliplatin and infusional 5-FU/LV(arm C). Oxaliplatin, at a dose of 85 mg/m2, was administered to patients in arms B and C intravenously over 2 hours in 250-500 ml of dextrose 5% in water (D5W) on day 1 only. A 200-mg/m2 dose of LV was administered simultaneously to arm C patients, in a separate bag using a Y-line, or alone to arm A patients, by i.v. infusion, over 2 hours. 5-FU was then administered to arms A and C patients, first as a bolus injection over 2-4 minutes at a dose of 400 mg/m2, then as a continuous infusion in 500 ml of D5W over 22 hours at a dose of 600 mg/m2. LV was repeated on day 2 of the cycle (arms A and C) followed by a 400-mg/m2 5-FU bolus and a 600-mg/m2 22-hour infusion. Treatment was repeated every 2 weeks. Response rate was the prespecified end point for accelerated approval. Time to progression (TTP) was a secondary end point. The prespecified primary comparison was between the 5-FU/LV regimen and the 5-FU/LV/ oxaliplatin combination regimen. The three arms were well balanced for patient prognostic factors. There were no complete responders. The partial response rates were 0%, 1%, and 9% for the 5-FU/LV, oxaliplatin, and oxaliplatin plus 5-FU/LV treatments, respectively (p = 0.0002, arm C versus arm A). The median times to radiographic tumor progression, based on available radiographs, were 2.7 months, 1.6 months, and 4.6 months, respectively (p < 0.0001, arm C versus arm A). Common adverse events associated with the combination treatment included peripheral neuropathy, fatigue, diarrhea, nausea, vomiting, stomatitis, and abdominal pain. Neutropenia was the major hematologic toxicity. Adverse events were similar in men and women and in patients <65 and > or =65 years of age, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia, and fatigue. Oxaliplatin in combination with infusional 5-FU/LV was approved for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed during or within 6 months of completion of first-line therapy with the combination of bolus 5-FU/LV and irinotecan. Approval was based on response rate and on an interim analysis of TTP. No results are available, at this time, that demonstrate a clinical benefit, such as improvement in disease-related symptoms or survival.
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PMID:FDA drug approval summaries: oxaliplatin. 1475 10

The oral fluoropyrimidine capecitabine (Xeloda) delivers 5-FU to the tumour site, thereby limiting the side effects and other complications associated with intravenous (i.v.) 5-FU. As an oral drug, capecitabine is preferred to 5-FU by many patients as it can be conveniently taken at home. In first-line metastatic colorectal cancer (MCRC), capecitabine results in superior response rates and equivalent progression-free and overall survival compared with i.v. 5-FU/LV. There is also increasing evidence for replacing i.v. 5-FU with capecitabine in combination with other anticancer agents (e.g. oxaliplatin and irinotecan) in MCRC and in the adjuvant treatment of early stage colon cancer. In anthracycline-pretreated metastatic breast cancer (MBC), adding capecitabine to docetaxel improves survival, time to progression (TTP) and response rates beyond docetaxel. Single-agent capecitabine is also effective in pretreated MBC and is a promising first-line therapy. Capecitabine has a favourable safety profile, the most frequent adverse events being hand-foot syndrome, stomatitis and diarrhoea. Because capecitabine is orally administered, it is possible to intervene promptly with dose interruption/reduction to resolve adverse events without impacting on efficacy. The increasing availability of capecitabine in the home-based setting requires careful consideration of the role of the oncology nurse, who is the key link between the patient and clinician for effective and efficient management.
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PMID:Development of and clinical experience with capecitabine (Xeloda) in the treatment of solid tumours. 1534 78

As capecitabine (Xeloda) is converted to 5-FU within tumours it can produce 5-FU-like side effects. However, diarrhoea, stomatitis, nausea, alopecia and neutropenia are significantly less frequent than with i.v. 5-FU. Hand-foot syndrome (HFS) is the only clinical adverse event occurring more often during capecitabine treatment. These findings in MCRC have also been confirmed in a large phase III trial in early stage colon cancer (X-Act adjuvant study) and phase II clinical trials in metastatic breast cancer. Because capecitabine is taken in the outpatient setting, the nurse and/or supervising clinician are responsible for educating patients how to use it correctly and on the nature/recognition/severity of adverse events. Patients need to be aware that temporary interruptions/dose modifications do not reduce the overall efficacy of capecitabine and will most likely lead to a resolution of side effects. Consequently, oncology nurses will be assuming a more significant and pivotal role in the efficient education and support of patients during home-based therapy with capecitabine.
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PMID:Management of adverse events and other practical considerations in patients receiving capecitabine (Xeloda). 1534 79

Colorectal cancers develop as a consequence of genomic instability. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and in most hereditary non-polyposis cancers. High frequency MSI has been associated with a favorable prognosis, however it is not clear whether this is because MSI-H tumors are inherently less aggressive or because they are more sensitive to chemotherapy. Chemotherapy with a combination of 5-fluorouracil and leukovorin or levamizole has been the standard of care for high risk stage II and stage III CRC; it is also used in stage IV CRC. Several in vitro studies have shown that colon cancer cell lines displaying MSI-H are less responsive to fluorouracil than microsatellite-stable cell lines. Human studies, all of them retrospective, yielded conflicting results. The selection of patients with CRC for 5-FU treatment has been based so far on the stage of the tumor rather than the biology of the tumor. Although surgical staging is highly predictive of survival, there are indications that the form of genomic instability within a patient's colorectal tumor has clinical implications, with and without 5-FU treatment. This review suggests that patients with MSI-H colorectal tumors may not benefit from 5-FU-based chemotherapy and can avoid its potential side effects (nausea, diarrhea, stomatitis, dermatitis, alopecia, and neurologic symptoms) that occur in half the treated patients. If confirmed by future prospective randomized controlled studies, these findings would indicate that microsatellite-instability testing should be conducted routinely and the results used to direct rational adjuvant chemotherapy in colon cancer.
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PMID:Biologic behavior of microsatellite-unstable colorectal cancer and treatment with 5-fluorouracil. 1610 79

1,2:5,6-Di-O-isopropylidene-alpha-d-glucofuranose on mild oxidation, reduction, fluorination, and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-d-glucopyranose. This was coupled with silylated N(4)-benzoyl cytosine. The nucleoside was deacetylated and after several subsequent protection and deprotection steps afforded the desired 3-fluoro-2-keto-beta-d-glucopyranosyl derivatives. These novel synthesized compounds were evaluated for antiviral and cytotoxic activities against rotavirus, vesicular stomatitis virus, and the human colon adenocarcinoma cell line Caco-2, and have a promising potential in combating the rotaviral infections and in the treatment of colon cancer. As compared to AZT, a nucleoside analogue of reverse transcriptase inhibitor, the novel synthesized 1-(3,4-dideoxy-3-fluoro-beta-d-glycero-hex-3-enopyranosyl-2-ulose)-N(4)-benzoyl cytosine showed to be more effective at lower concentrations in inhibition of rotavirus infection as well as in the same range of antitumor activity.
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PMID:Fluoro-ketopyranosyl nucleosides: synthesis and biological evaluation of 3-fluoro-2-keto-beta-D-glucopyranosyl derivatives of N4-benzoyl cytosine. 1707 49


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