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)

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.
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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.
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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.
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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.
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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.
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PMID:Doxil-induced regression of pleuro-pulmonary metastases in a patient with malignant meningioma. 1263 20

Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide exposure and subsequent depletion of O-alkylguanine alkyltransferase may improve the activity of temozolomide. The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity, their formulation and no significant overlapping toxicities. We conducted a study of a prolonged schedule of temozolomide (orally on days 1-7 and 15-21) plus Caelyx (day 1) every 28 days. Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to four dose levels (DL; temozolomide+Caelyx, mg/m): DL1: 100+30 (n=3 patients), DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6 patients). Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC >/=7 days). Treatment delays and/or dose reductions (due to hematological toxicity) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide 125 mg/m (daily for 7 days every other week) plus Caelyx 40 mg/m (day 1 every 4 weeks). Other toxicities were mild. Antitumor activity was observed in eight patients, including one complete response (melanoma), three partial responses (one melanoma, two sarcomas) and four patients with stable disease (three melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions. This schedule of temozolomide allowed higher dose intensity (1750 mg/m in 4 weeks) compared to the standard 5-day regimen (1000 mg/m in the same amount of time).
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PMID:Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx) in advanced solid cancers. 1516 25

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.
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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.
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PMID:The role of the liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer. 1571 40

Nursing care of the patient receiving chemotherapy includes patient education and drug administration, as well as ongoing assessment, early identification, and intervention for side effects. Two liposomal anthracyclines are available in the United States, pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and liposomal daunorubicin (DaunoXome [DNX]). Because of their unique liposomal formulations, the administration and toxicity profiles of these agents are different from those of conventional anthracyclines, as well as each other. Common severe toxicities of conventional anthracycline treatment such as nausea/vomiting, alopecia, and neutropenia are less frequent and less severe during liposomal anthracycline treatment, and cumulative-dose cardiotoxicity is rare, particularly with PLD therapy. Dose-related adverse events with liposomal anthracycline therapy include stomatitis and neutropenia, and more frequent doses of PLD are associated with hand-foot syndrome. Ongoing nursing assessment, patient education, and adjustments to the dose or dose-schedule can reduce the severity or frequency of these toxicities. Nurses must be aware of the unique characteristics of liposomal anthracycline therapy to provide optimal patient education and nursing care.
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PMID:Liposomal anthracycline administration and toxicity management: a nursing perspective. 1571 43

The need for effective, well-tolerated, and convenient therapies for patients with advanced ovarian cancer has led researchers to continually refine chemotherapeutic regimens to balance efficacy with safety and tolerability in order to maintain or improve patient quality of life. In this article, we review current strategies for the optimal dosing of pegylated liposomal doxorubicin (DOXIL; Tibotec Therapeutics, a division of Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.tibotec.com; Caelyx, Schering-Plough Corporation, Kenilworth, NJ, http://www.sch-plough.com) in relapsed ovarian cancer. Pegylated liposomal doxorubicin has demonstrated efficacy in the treatment of recurrent/resistant ovarian cancer in several clinical trials utilizing a dose of 50 mg/m2 every 4 weeks. The most common adverse events associated with pegylated liposomal doxorubicin treatment in these studies-hand-foot syndrome (HFS, also known as palmar-plantar erythrodysesthesia) and stomatitis-are schedule and dose dependent, respectively, and do not typically lead to discontinuation of therapy. Several phase II and retrospective studies support the use of pegylated liposomal doxorubicin 40 mg/m2 every 4 weeks (dose intensity of 10 mg/m2 weekly) to optimize clinical efficacy and minimize the occurrence of schedule- and dose-related adverse events in patients with recurrent/relapsed ovarian cancer. Further reductions in dose intensity are necessary for use in combined chemotherapy regimens. Antitumor activity was maintained, with reduced incidences of HFS and stomatitis. Given the chronic course of ovarian cancer, the improved tolerability profile of pegylated liposomal doxorubicin 40 mg/m2 combined with a convenient once-monthly dosing schedule may translate into an improved quality of life for patients with ovarian cancer.
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PMID:Pegylated liposomal doxorubicin: optimizing the dosing schedule in ovarian cancer. 1579 24


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