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

In an attempt to improve upon the 43%-48% regression rates noted for various CAP regimens consisting of cyclophosphamide, doxorubicin (Adriamycin), and cis-diamminedichloroplatinum(II) in various doses and schedules, triazinate was added to that three-drug combination, and the new combination (T-CAP) was evaluated in patients with advanced adenocarcinoma of the lung. T-CAP produced a regression rate of 57% with a 7-week increase in overall median time to progression and a 4-week increase in overall median survival compared to the best of the CAP schedules. More stomatitis and dermatitis were noted with the new combination, but myelosuppression was similar to that of the CAP regimens. These data suggest that further studies with triazinate should be conducted in patients with adenocarcinoma of the lung.
 ...
PMID:Phase II evaluation of the combination of triazinate, cyclophosphamide, doxorubicin, and cis-diamminedichloroplatinum(II) in patients with advanced adenocarcinoma of the lung. 719 2

Thirty patients with unresectable adenocarcinoma of the lung were treated with high doses of 5-fluorouracil, Adriamycin, and mitomycin-C (Hi-FAM). Objective responses were seen in ten patients (one complete and nine partial remissions). No patient with pleural disease responded to treatment. Responses were seen in all other sites of involvement including liver. In a subgroup of patients younger than 65 years, who had not had prior treatment, and who had a performance status of greater than 60 (Karnofsky), an overall response rate of 50% was realized. The overall median survival for responding patients was 10+ months while nonresponders had a median survival of 5.21 months. Patients who had had prior irradiation had a median survival of 4.81 months compared with patients who had not had any prior treatment, whose median survival was 8.45 months. Toxicity was substantial and included primarily bone marrow suppression and stomatitis. Elderly patients with poor performance status and prior treatment tolerated therapy less well. These results indicate that Hi-FAM is useful in selected groups of patients with advanced adenocrcinoma of the lung.
 ...
PMID:5-fluorouracil, adriamycin, and mitomycin-C (Hi-FAM) chemotherapy for adenocarcinoma of the lung. 723 86

Three hundred and thirty-six patients with a variety of tumors were treated with Adriamycin given weekly as an iv bolus of 1 mg/kg with subsequent doses adjusted for hematologic toxicity. This weekly schedule, not utilizing a loading course, resulted in only a 20% incidence of stomatitis. The number of evaluable patients and the percent with objective responses (respectively) according to tumor type were: lung (57 patients, 14%); sarcoma (62, 24%); breast (31, 35%); transitional cell carcinoma (17, 29%); non-Hodgkin's lymphoma (17, 29%); head and neck (16, 13%); colorectal (13, 0); ovarian (eight, 25%); and other (53, 11%). These response frequencies are comparable to those reported for every-3-week regimens using 60-75 mg/m2 of Adriamycin. Sixteen patients were given 450-550 mg/m2 of Adriamycin, five were given 550-600 mg/m2, and ten were given greater than 600 mg/m2. None of the study patients developed definite evidence of drug-induced congestive heart failure. Therefore, Adriamycin given as a weekly schedule provides a clinically effective alternative to the every-3-week schedule of administration. The weekly schedule is associated with tolerable toxicity and a decreased risk of developing drug-induced congestive heart failure.
 ...
PMID:Adriamycin given as a weekly schedule without a loading course: clinically effective with reduced incidence of cardiotoxicity. 737 58

A liposome-entrapped liposome form of Adriamycin (Lip-ADM) has been demonstrated to cause less myocardial and gastrointestinal toxicity than free ADM. In the present study, Lip-ADM prepared by the remote loading method was administered to 3 patients with metastatic adenocarcinoma of the liver via a reservoir with the catheter located in the proper hepatic artery. The primary tumor was gastric cancer in 2 patients and sigmoid colon cancer in 1. Lip-ADM was administered at doses of 10, 20 or 50 mg per time. The total ADM dose was 170, 490, and 760 mg, respectively. No severe adverse effects, such as nausea, vomiting, stomatitis, alopecia or cardiotoxicity, were observed in any of the patients. Although mild leukocytopenia (2,800/microliters) was observed in 1 patient, anemia or thrombocytopenia did not occur. The survival time was respectively 6, 15, and 17 months from the start of Lip-ADM administration. A partial response was obtained in 1 patient and stable disease in 1 patient. Administration of Lip-ADM via a reservoir appears to be a useful treatment for patients with metastatic adenocarcinoma of the liver, since the low toxicity of this preparation allows an increase of the total dose of ADM.
 ...
PMID:Intra-arterial liposomal adriamycin for metastatic adenocarcinoma of the liver. 758 1

Treatment options for patients with stage IV melanoma are limited. Based on differences in the toxicity and activity profiles of pegylated liposomal doxorubicin (doxil) compared to standard doxorubicin, we have conducted a phase II trial of doxil for patients with metastatic melanoma. Doxil was administered as a 60-90 min intravenous infusion every 21 days. The starting dose was 60 mg/m2 for the initial nine patients, but was subsequently reduced to 50 mg/m2 for the remainder due to toxicity issues. Thirty-two patients were enrolled in the trial. Ninety-one percent had received prior systemic therapy. There were no complete responses and two partial responses for an overall response rate of 6%. The dominant side effects included hand-foot syndrome, rash (occasionally severe), and stomatitis, consistent with reports from other trials using similar doses and schedules. We conclude that doxil does not demonstrate sufficient activity in metastatic melanoma to warrant further investigation into its use in this setting.
 ...
PMID:Phase II trial of doxil for patients with metastatic melanoma refractory to frontline therapy. 1042 8

Doxil, a doxorubicin formulation of polyethylene glycol-coated liposomes, has anti-tumor activity against Kaposi's sarcoma and other solid tumors with mild myelosuppression, minimal hair loss and a low risk of cardiotoxicity. Non-liposomal doxorubicin has modest activity in hormone-refractory prostate cancer (HRPC) with considerable toxicity. A pilot study of Doxil was conducted in 15 patients with HRPC. Doxil was administered i.v. using two regimes of equal dose intensity, either 45 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks. Plasma levels of doxorubicin were analyzed in 10 patients. The most common side effect was stomatitis with a higher incidence at the 60 mg/m2 dose level. In contrast, hand-foot syndrome was more frequent and severe in patients treated with the 3 week schedule of 45 mg/m2. Three patients responded to treatment (based on objective response in one patient and reduction of PSA level greater than 50% in the other two) and two patients had stable disease, all of them receiving 60 mg/m2. Pharmacokinetic analysis shows a proportional increase of plasma drug levels with dose and the characteristic long circulation time of Doxil with half-lives in the range of 3 days, somewhat longer than previously reported. In conclusion, Doxil at 60 mg/m2 every 4 weeks appears to be active against HRPC, but severe mucocutaneous toxicities prevented further investigation of this regime.
 ...
PMID:Doxil (Caelyx): an exploratory study with pharmacokinetics in patients with hormone-refractory prostate cancer. 1078 95

Standard chemotherapy for advanced epithelial ovarian cancer is a combination of platinum-paclitaxel. One strategy to improve the outcome for patients is to add other agents to standard therapy. Doxil is active in relapsed disease and has a response rate of 25% in platinum-resistant relapsed disease. A dose finding study of doxil-carboplatin-paclitaxel was therefore undertaken in women receiving first-line therapy. Thirty-one women with epithelial ovarian cancer or mixed Mullerian tumours of the ovary were enrolled. The doses of carboplatin, paclitaxel and doxil were as follows: carboplatin AUC 5 and 6; paclitaxel, 135 and 175 mg m(-2); doxil 20, 30, 40 and 50 mg m(-2). Schedules examined included treatment cycles of 21 and 28 days, and an alternating schedule of carboplatin-paclitaxel (q 21) with doxil being administered every other course (q 42). The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m(-2) and doxil 30 mg m(-2) q 21. Reducing the paclitaxel dose to 135 mg m(-2) did not allow the doxil dose to be increased. Delivering doxil on alternate cycles at doses of 40 and 50 mg m(-2) also resulted in dose-limiting toxicities. The recommended doses for phase II/III trials are carboplatin AUC 6, paclitaxel 175 mg m(-2), doxil 30 mg m(-2) q 28 or carboplatin AUC 5, paclitaxel 175 mg m(-2), doxil 20 mg m(-2) q 21. Grade 3/4 haematologic toxicity was common at the recommended phase II doses but was short lived and not clinically important and non-haematologic toxicities were generally mild and consisted of nausea, paraesthesiae, stomatitis and palmar plantar syndrome.
 ...
PMID:A phase I dose-finding study of a combination of pegylated liposomal doxorubicin (Doxil), carboplatin and paclitaxel in ovarian cancer. 1198 67

Metastatic meningioma is a rare disease, which has no effective chemotherapy. We report on a treatment of this condition with Doxil, a liposomal doxorubicin formulation. A 60-year-old woman with massive pleuro-pulmonary metastases from recurrent cranial meningioma was treated with Doxil (50-37.5 mg/m2) for 18 months with near-complete resolution of metastases and disappearance of pleural fluid. The only significant toxicities observed were stomatitis and hand-foot syndrome, which resolved with dose reduction and increase of dosing intervals. Doxil was cleared very slowly in this patient with a monoexponential half-life of 108 h. The patient remains in near-complete response for 6 months after treatment discontinuation. This is the first report on an effective chemotherapy in a patient with typical metastatic meningioma. The exact mechanism accounting for such an effective drug action is not clear, but may be related to a particularly high microvascular permeability to the liposome carriers in these metastatic lesions.
 ...
PMID:Doxil-induced regression of pleuro-pulmonary metastases in a patient with malignant meningioma. 1263 20

Conventional chemotherapy regimens for the treatment of advanced Kaposi's sarcoma (KS) show limited efficacy and considerable toxicity. Liposomal anthracyclines with potential utility in KS include pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), daunorubicin citrate liposome (DaunoXome [DNX]), and nonpegylated liposomal doxorubicin (Myocet [NPLD]). Preclinical data showed that pegylated liposomes accumulate preferentially in highly vascularized KS lesions. In randomized clinical trials, PLD induced higher response rates than did the conventional combination chemotherapy regimens, bleomycin + vincristine (BV) and BV + conventional doxorubicin (ABV); DNX produced a response rate comparable to that of ABV. NPLD has not been compared with conventional chemotherapy for KS. PLD and DNX were associated with less toxicity compared with BV or ABV, including less alopecia and fewer gastrointestinal and neurologic side effects. Grade 3/4 myelosuppression was common with both PLD and DNX; stomatitis and infusion reactions occurred with PLD treatment, but hand-foot syndrome was relatively infrequent in the dose schedules used for KS. Health-related quality of life was improved in several domains in patients treated with PLD or DNX compared with ABV.
 ...
PMID:Use of liposomal anthracyclines in Kaposi's sarcoma. 1571 37

For patients whose breast cancers are not responsive to endocrine therapy, there are a large number of cytotoxic drugs that will induce a response. In spite of the introduction of new, very active drugs such as the taxanes, vinorelbine, capecitabine, gemcitabine, and trastuzumab, the anthracyclines are still as active as any--and more active than most--drugs used to treat breast cancer. Their inclusion in combinations to treat early and advanced disease prolongs survival. However, they cause nausea, vomiting, alopecia, myelosuppression, mucositis, and cardiomyopathies. There is no evidence that increasing the dose of conventional anthracyclines or any other of the cytotoxics beyond standard doses will improve outcomes. Schedule may be more important than dose in determining the benefit of cytotoxics used to treat breast cancer. Weekly schedules and continuous infusions of 5-fluorouracil and doxorubicin may have some advantages over more intermittent schedules. Liposomal formations of doxorubicin reduce toxicity, including cardiotoxicity; theoretically they should also be more effective because of better targeting of tumor over normal tissues. Both pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and liposomal doxorubicin (Myocet [NPLD]) appeared to be as effective as conventional doxorubicin and much less toxic in multiple phase II and phase III studies. PLD has been evaluated in combinations with cyclophosphamide, the taxanes, vinorelbine, gemcitabine, and trastuzumab, and NPLD has been evaluated in combination with cyclophosphamide and trastuzumab. Both liposomal anthracyclines are less cardiotoxic than conventional doxorubicin. The optimal dose of PLD is lower than that of conventional doxorubicin or NPLD. Patients treated with PLD have almost no alopecia, nausea, or vomiting, but its use is associated with stomatitis and hand-foot syndrome, which can be avoided or minimized with the use of proper dose-schedules. In contrast, the optimal dose-schedule of NPLD is nearly identical to that of conventional doxorubicin. The toxicity profile of NPLD is similar to that of conventional doxorubicin, but toxicities are less severe and NPLD is better tolerated than conventional doxorubicin at higher doses.
 ...
PMID:The role of the liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer. 1571 40


<< Previous 1 2 3 4 Next >>