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 combination of trabectedin (T) and doxorubicin (D) was brought into clinical development in soft tissue sarcoma (STS) and advanced breast cancer (ABC) because of its in vitro and in vivo additive anti-tumour effect, the fact that there are no overlapping toxicities and the anti-tumour activity of T in those tumours. Feasibility and anti-tumour activity of T+D administered every 3 weeks were evaluated in 38 patients (STS=29, ABC=9) untreated for advanced disease. D was given at 60 mg/m(2) and T at escalating doses from 600 to 800 microg/m(2), which was the maximum tolerated dose due to dose-limiting febrile neutropenia and asthenia. The recommended dose--given to 18 patients in total--was 700 microg/m(2) T with 60 mg/m(2) D. The pharmacokinetic profile of T and D at cycle 1 was analysed in 20 patients. The most common toxicities included a severe but reversible ASAT/ALAT increase (94%), nausea/vomiting, neutropenia, asthenia/fatigue, stomatitis. Partial response and stable disease were assessed in 18% and 56% of STS patients and in 55% and 33% of ABC patients. No pharmacokinetic interaction between T and D was observed. The lack of cumulative toxicity and related complications and the promising activity in STS support further development of T+D.
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PMID:Phase I clinical and pharmacokinetic study of trabectedin and doxorubicin in advanced soft tissue sarcoma and breast cancer. 1911

Although docetaxel monotherapy has shown clinical benefits for previously treated patients with advanced non-small cell lung cancer (NSCLC), the efficacy of salvage docetaxel chemotherapy for elderly patients or patients with poor performance status (PS) is controversial. Therefore, we conducted a phase II trial to evaluate the safety and efficacy of weekly low-dose docetaxel monotherapy in these patients. Forty NSCLC patients, who had been previously treated with one or more chemotherapy regimens, received docetaxel at a dose of 25 mg/m(2) weekly on days 1, 8, and 15 of a 28-day cycle. All patients were >or=65 yr or had a PS of grade 2 in the cases of <65 yr. Weekly low-dose docetaxel was well-tolerated. Grade 3/4 non-hematologic toxicities were rare; fatigue in 3 patients (8%), anorexia in 3 patients (8%) and stomatitis in 2 patients (5%). Grade 3/4 neutropenia was noted in only one patient (3%). By intent-to-treat analysis, nine patients (23%) had partial responses and eleven patients (28%) demonstrated stable disease. The median progression-free survival and overall survival were 9.9 weeks and 37.7 weeks, respectively. Weekly low-dose docetaxel therapy provides a reasonable alternative for NSCLC salvage treatment in pretreated elderly patients or in patients with a reduced PS.
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PMID:Weekly low-dose docetaxel for salvage chemotherapy in pretreated elderly or poor performance status patients with non-small cell lung cancer. 1911 42

The objective of this study was to evaluate the efficacy and safety of the POF regimen (biweekly 5-fluorouracil/leucovorin combined with paclitaxel and oxaliplatin) as first-line treatment for advanced gastric cancer (AGC). Twenty-seven previously untreated patients with advanced adenocarcinoma of the gastric or gastroesophageal junction were eligible for this study. The chemotherapy regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) and leucovorin (400 mg/m(2)), administered simultaneously over a 2-hour infusion period, followed by an infusion of 5-fluorouracil (2400 mg/m(2)) over a 46-hour period. Twenty-one patients had measurable lesions: four complete responses, eight partial responses and seven stable diseases. At a median follow-up of 610 days, median survival was 348 days. Frequent grade 3 to 4 toxicities were: neutropenia (29.6%), stomatitis (7.4%), nausea (7.4%), vomiting (7.4%), hepatic dysfunction (3.7%), and fatigue (18.5%). No treatment-related deaths occurred. The POF regimen appears to be efficacious and is well tolerated in patients with AGC.
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PMID:A phase II study of 5-fluorouracil/leucovorin in combination with paclitaxel and oxaliplatin as first-line treatment for patients with advanced gastric cancer. 1912 74

In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3-4 toxicity included fatigue (n=3), neutropenia (n=2), thrombocytopenia (n=2), interstitial pneumonitis (n=1), stomatitis (n=1) and diarrhea (n=1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70(S6)K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. Investigation of alternate dosing schedules and use in combinations is indicated.
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PMID:Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma. 1926 29

The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been reported to be active against metastatic gastric cancer (MGC) and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. The sequential combination of S-1 (tegafur, oxonic acid, 5-chloro-2,4-dihydroxypyridine) followed by CDDP for MGC was investigated. A phase I trial applying increasing doses of oral administration of S-1 (65-80 mg/m(2)) for 21 days and increasing doses of CDDP (60-80 mg/m(2)) on day 22 every 35 days was conducted in order to determine the maximum tolerated dose (MTD) and recommended phase II dose. Patients with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, ECOG performance status less than 3 and adequate organ functions were eligible for the study. Three patients were treated at each dose level with escalation based on toxicity. Fifteen patients were included and evaluated for dose-limiting toxicity (DLT) and MTD. DLT included NCICTC grade 3 anorexia and fatigue in patients treated at S-1 80 mg/m(2) and CDDP 80 mg/m(2) (dose level 5). The other toxicities, grade 3 or higher, included neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. Therefore, the recommended dose was a combination of S-1 at 80 mg/m(2) and CDDP at 70 mg/m(2). This sequential administration of S-1 and CDDP every 35 days is tolerable and warrants a phase II trial. A multicenter phase II study is currently under way.
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PMID:Phase I study of the sequential administration of S-1 and cisplatin for metastatic gastric cancer. 1944 94

A 77-year-old man with advanced esophageal carcinoma and lymph node swelling of abdomen and mediastinum, underwent neoadjuvant chemotherapy (NAC) with 5-FU/CDDP. Adverse reactions were general fatigue and nausea of grade 3 and stomatitis of grade 2. Primary tumor and lymph node swelling revealed remarkable effectiveness after 1 course of NAC, so 2 courses of NAC were given. The esophageal carcinoma was not found by endoscopy, and a biopsy specimen revealed inflammatory granulation. Lymph node on CT examination disappeared in the abdomen and reduced in the mediastinum. Because of retention of lymph node swelling, radical resection of the esophageal carcinoma was performed. Pathologic examination of the resected specimen revealed no malignant cells in the esophagus, and 3 lymph node metastases (pStage III). He had no recurrence in 15 months after the operation. Because NAC was markedly effective for primary tumor and lymph node of esophageal carcinoma, a radical operation was performed.
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PMID:[A case of pathologic complete response of primary esophageal carcinoma treated with 5-FU/CDDP as neoadjuvant chemotherapy]. 1946 Nov 90

Sunitinib is a novel, oral, multi-targeted tyrosine kinase inhibitor with antiproliferative effects against cancer cells and antiangiogenic properties. Sunitinib was recently approved for the first-line treatment of patients with advanced renal cell carcinoma (RCC) and for the treatment of patients with gastrointestinal stromal tumours (GIST) after disease progression or intolerance to imatinib therapy. The main purpose of this benefit-risk assessment is to review data on sunitinib efficacy along with its toxicity in patients with GIST and RCC. Sunitinib demonstrates a high level of efficacy with acceptable tolerability using either the 50 mg daily oral dosing for 4 weeks every 6 weeks or a continuous daily administration schedule at a lower dose. Hypertension and asthenia appear to be the most common adverse effects with sunitinib. Diarrhoea, anorexia, disgeusia, stomatitis and skin toxicity are other clinically relevant toxicities. Fatigue may, at least in part, be related to the development of hypothyroidism during sunitinib therapy. Skin toxicity consists of bullous lesion in the soles and palms that may require treatment discontinuation for a few days and/or dose reduction. Thyroid hormone levels should be monitored during treatment with sunitinib, with the occurrence of clinical signs of hypothyroidism needing treatment with levothyroxine sodium. Hypertension usually requires standard antihypertensive therapy and treatment discontinuation is less frequently necessary. Mild neutropenia and thrombocytopenia usually require no intervention. A decrease in left ventricular ejection fraction is a rare but potentially life-threatening complication. Although usually well tolerated, sunitinib needs to be administered cautiously with medical follow-up in patients with cancer to prevent, avoid and treat adverse effects in order to improve patient compliance. Its established antitumor activity requires attempting to maintain the highest tolerable dose in individual patients. Current oral formulations allow physicians to modulate dosages (between 25 and 50 mg/day) and/or schedules (4 weeks on, 2 weeks off or continuous administration) to optimize the benefit-risk profile of sunitinib in individual patients.
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PMID:Benefit-risk assessment of sunitinib in gastrointestinal stromal tumours and renal cancer. 1967 Sep 13

Angiogenesis is essential for normal tissue and even more so for solid malignancies. At present, inhibition of tumor angiogenesis is a major focus of anticancer drug development. Bevacizumab, a humanized antibody against VEGF, was the first antiangiogenic agent to be approved for advanced non-small cell lung cancer, breast cancer and colorectal cancer. The most commonly observed adverse events are hypertension, proteinuria, bleeding and thrombosis. Sunitinib, a small molecule blocking intracellular VEGF, KIT, Flt3 and PDGF receptors, which regulate angiogenesis and cell growth, is approved for the treatment of advanced renal cell cancer (RCC) and malignant gastrointestinal stromal tumor. The most frequent adverse events include hand-foot syndrome, stomatitis, diarrhea, fatigue, hypothyroidism and hypertension. Sorafenib, an oral multikinase inhibitor, is approved for the second-line treatment of advanced RCC and upfront treatment of advanced hepatocellular carcinoma. Most common adverse events with sorafenib are dermatologic (hand-foot skin reaction, rash, desquamation), fatigue, diarrhea, nausea, hypothyroidism and hypertension. More recently, cardiovascular toxicity has increasingly been recognized as a potential adverse event associated with sunitinib and sorafenib treatment. Elderly patients are at increased risk of thromboembolic events when receiving bevacizumab, and potentially for cardiac dysfunction when receiving sunitinib or sorafenib. The safety of antiangiogenic drugs is of special concern when taking these agents for longer-term adjuvant or maintenance treatment. Furthermore, newer investigational antiangiogenic drugs are briefly reviewed.
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PMID:Antiangiogenic drugs in oncology: a focus on drug safety and the elderly - a mini-review. 1994 Apr 66

Whether elderly patients with metastatic esophageal, gastroesophageal, and gastric cancer do as well with chemotherapy as their younger counterparts was investigated in this pooled analysis. In total, 367 patients from 8 consecutive, first-line trials were included: i) etoposide + cisplatin; ii) 5-fluorourucil + leucovorin; iii) 5-fluorouracil + levamisole; iv) irinotecan; v) docetaxel + irinotecan; vi) oxaliplatin + capecitabine; vii) docetaxel + capecitabine; and viii) bortezomib + paclitaxel + carboplatin. One hundred and fifty-four (42%) patients were > or =65 years old (range: 65-86), and 213 younger (range: 20-64). Elderly patients had worse performance scores (2-3): 19 vs. 8% (p<0.0001). Rates of grade 3+ adverse events across all chemotherapy cycles in univariate and multivariate analyses (adjusted for gender, performance score, and stratified by individual study) were higher among elderly patients. Rates of neutropenia, fatigue, infection, and stomatitis in elderly vs. younger patients were 31 vs. 29% (p=0.02 by multivariate analyses); 15 vs. 5% (p=0.01); 9 vs. 4% (p=0.03); 6 vs. 1% (p=0.04). In contrast, duration of chemotherapy, overall survival, and progression-free survival were comparable. Although age should not preclude trial entry, these adverse event rates suggest a need to develop more tolerable regimens for older patients with these malignancies.
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PMID:Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: a pooled analysis of eight consecutive North Central Cancer Treatment Group (NCCTG) trials. 2012 80

Sustained elevation of serum methotrexate (MTX) concentrations (>1.0 microM) for 48 h (48-h value) has been found to have predictive significance for the development of toxicity. However, we sometimes experience severe adverse events during high-dose (HD) MTX therapy even if serum MTX concentrations comply with recommended values. We performed a retrospective study to identify predictors for occurrence of adverse events and examined whether only the 48-h value is a statistically significant predictor for clinical adverse events during HD MTX therapy. The subjects were 32 hematological patients (n = 58 episodes) treated with MTX at Kyoto Prefectural University of Medicine between February 2003 and July 2007. Ordered logistic regression analysis was used to identify predictors for occurrence of adverse events. The predictive factors identified were: 24-h continuous infusion therapy (24-h C-IV) (long infusion time) [odds ratio (OR) = 2.890, confidence interval (CI) =1.493-5.594; P = 0.0016] for fatigue, higher dose [OR = 2.282, CI = 1.287-4.046; P = 0.0048] and combination chemotherapy [OR = 2.177, CI = 1.059-4.477; P = 0.0344] for stomatitis, and 24-h C-IV [OR = 2.573, CI = 1.101-6.016; P = 0.0291] for neutropenia. We found that only the 48-h value was not a predictor for clinical adverse events for HD MTX therapy. A major limitation of the present study was the small number of participants. However, our findings suggest that there is evidence that a long infusion time is a significant predictor for general fatigue and neutropenia, while a higher dose and combination chemotherapy are predictors for stomatitis.
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PMID:Statistical examination to determine whether only 48-h value for serum concentration during high-dose methotrexate therapy is a predictor for clinical adverse events using ordered logistic regression analysis. 2042 13


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