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)

Encapsulation in polyethylene glycol-coated (pegylated; Stealth) liposomes alters the pharmacokinetic characteristics, and hence the safety and tolerability profile, of doxorubicin. Pegylated liposomal doxorubicin administered as a single agent is generally well tolerated. Grade III/IV leucopenia, stomatitis and palmar-plantar erythrodysaesthesia affected 16, 6 and 18% of solid tumour patients, respectively. Other adverse effects included nausea and vomiting and alopecia. Acute hypersensitivity infusion reactions have been reported in up to 9% of patients in some studies. Recently published data from a phase II trial in patients with refractory ovarian cancer showed no alopecia or cardiotoxicity and little nausea and vomiting after pegylated liposomal doxorubicin. Unlike free doxorubicin, pegylated liposomal doxorubicin is not a vesicant. Preliminary data, not yet confirmed in comparative studies, suggest that the pegylated liposomal formulation may be less cardiotoxic than free doxorubicin. Mucositis, however, appears to be increased. Studies to determine optimal dosing schedules and safety of pegylated liposomal doxorubicin in combination with other agents are ongoing.
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PMID:Safety aspects of pegylated liposomal doxorubicin in patients with cancer. 936 59

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.
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PMID:A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors. 938 46

Vinorelbine (Navelbine) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.
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PMID:A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors. 974 May 42

We analyzed the efficacy and toxicity of docetaxel in patients with ovarian cancer who failed previous chemotherapy with platinum. Fifty-five patients with measurable ovarian cancer were entered in this Phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of 100 mg/m2 docetaxel given i.v. every 3 weeks. Because of hypersensitivity reactions, premedication with steroids and antihistamine was initiated during the study. Twenty-two (40%) patients responded (there were 3 complete responders and 19 partial responders). Twenty-one (38%) patients had stable disease. The median survival was 10 months. The main toxicity was neutropenia (98% of patients), with 13 episodes of neutropenic fever. Cumulative fluid retention was the main reason for dose modification and required a combination of diuretics and steroids for palliation. Other side effects were alopecia (100%); anemia (87%); dermatitis (67%); gastrointestinal disorders (53%); stomatitis (49%); neurotoxicity (45%); excessive lacrimation (33%); and hypersensitivity reactions (11%), which in one case were life threatening (loss of consciousness, fluid resuscitation). Docetaxel as a single agent proved to be active in heavily pretreated ovarian cancer patients but is associated with significant side effects. Objective toxicity consisted mainly of neutropenia and fluid retention. Neutropenia was dose limiting and required therapy with granulocyte colony-stimulating factor. Fluid retention was improved but not eliminated by diuretics and corticosteroids. Additional studies of docetaxel in ovarian carcinoma are indicated to define the activity in relation to paclitaxel and in platinum combination therapy.
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PMID:Phase II study of docetaxel in patients with epithelial ovarian carcinoma refractory to platinum. 981 38

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.
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PMID:[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group]. 983 8

Topotecan does not convincingly alter the grim prognosis of ovarian cancer in failure or relapse after treatment with platinum salts. The only comparative trial has not yet been published; available results suggest that 20% of women had at least a partial response on topotecan, compared to 14% on paclitaxel (no statistically significant difference). The place of paclitaxel in the treatment of ovarian cancer also remains to be determined, especially in combination with other drugs. Like paclitaxel, topotecan has marked haematological and gastrointestinal toxicity: nausea, vomiting, diarrhoea and stomatitis. Topotecan solution does not contain the solvent Cremophor EL degrees , contrary to paclitaxel solution. It does not therefore require preliminary steroid administration, and does not prohibit the use of PVC-based infusion devices.
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PMID:Topotecan: new preparation. No proven benefit. 1018 83

The purpose of this study was to analyze the efficacy and toxicity of a high dose of paclitaxel in patients with ovarian cancer refractory to platinum chemotherapy. Another phase II study of hydroxyurea was run in the same patient population. Fifty patients with measurable ovarian cancer were entered on this phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of 250 mg/m2 of paclitaxel given by continuous intravenous infusion over 24 h every 3 weeks. Patients with disease unresponsive to paclitaxel could then be crossed over to hydroxyurea, and vice versa. Twenty-five (53%) out of 47 evaluable patients had a response (two complete responses and 23 partial responses). Twelve (26%) patients had stable disease. The median survival was 11.3 months. The main toxic effect was neutropenia (98% of patients) with 28 (9%) episodes of neutropenic fever. Neutropenia required therapy with granulocyte colony-stimulating factor. Other side effects were alopecia (100%), anemia (98%), gastrointestinal problems (57%), stomatitis (27%), and neurotoxicity (55%). Paclitaxel administered at a high dose as a single agent proved to be very active in patients who had platinum-refractory ovarian cancer and was well tolerated. Further studies of high-dose paclitaxel in patients with ovarian carcinoma are indicated.
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PMID:Long-term results and pharmacokinetics of high-dose paclitaxel in patients with refractory epithelial ovarian carcinoma. 1124 Jul 42

We evaluated the tolerability and toxicity attributed to pegylated liposomal doxorubicin (PL-DOX) in women with recurrent or refractory ovarian cancer, and reviewed procedures to prevent or treat toxicity induced by the agent. Medical records of 13 women who received PL-DOX between October 1997 and December 2000 were reviewed. Patients 1-8 received PL-DOX once it was added to the hospital formulary in 1997. Patients 9-13 received it after medical staff education. Data on premedications, number of cycles, dosage, length of infusion, tolerability, side effects, and indicators for response were collected. The median number of cycles and cumulative dose/patient of PL-DOX were higher (6 and 420 mg) in the second group than in the first group (2 and 240 mg). Patient factors such as duration of disease and number of chemotherapy cycles influenced tolerability. One patient experienced a life-threatening adverse reaction within minutes of receiving the first dose. Treatment was discontinued, and she was resuscitated successfully. Other dose- or treatment-limiting complications (neutropenia, stomatitis, plantar-palmar erythrodysesthesia) were documented. Toxicity management consisted of dosage reduction or treatment delay; treatment often was discontinued. Patients with recent disease tolerated more cycles of PL-DOX when given early in recurrence compared with heavily pretreated women with long-standing disease. Tolerability was not necessarily indicative of response. The agent is simple to administer, but its tolerability and lack of uniform toxicity management remain concerns.
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PMID:Pegylated liposomal doxorubicin: tolerability and toxicity. 1140 Nov 88

Ideally, an oncolytic virus will replicate preferentially in malignant cells, have the ability to treat disseminated metastases, and ultimately be cleared by the patient. Here we present evidence that the attenuated vesicular stomatitis strains, AV1 and AV2, embody all of these traits. We uncover the mechanism by which these mutants are selectively attenuated in interferon-responsive cells while remaining highly lytic in 80% of human tumor cell lines tested. AV1 and AV2 were tested in a xenograft model of human ovarian cancer and in an immune competent mouse model of metastatic colon cancer. While highly attenuated for growth in normal mice, both AV1 and AV2 effected complete and durable cures in the majority of treated animals when delivered systemically.
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PMID:VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. 1458 54

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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