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)

N,N',N''-triethylenethiophosphoramide (thiotepa) is a polyfunctional alkylating agent similar in structure to nitrogen mustard. Thiotepa (synthesized by American Cyanamid Company, Wayne, NJ) underwent clinical trials in the 1960s that showed that it was active against a wide variety of tumors. At a standard dose level (10 to 30 mg/m2), the dose-limiting toxicity is myelosuppression; other toxicities are infrequent. Therefore, high-dose phase I evaluation was encouraged by these observations. Approximately 217 patients have been treated with single-agent high-dose thiotepa administered intravenously daily over 2 hours for 3 days followed by hematopoietic stem cell rescue to prevent prolonged myelotoxicity. The total doses administered ranged from 135 to 1,575 mg/m2. As anticipated, myelotoxicity was substantial, with 180 mg/m2 being the highest dose not requiring stem cell rescue to ensure hematopoietic recovery. Extramedullary toxicities consisted of stomatitis, dermatitis, hepatoxicity, and central nervous system (CNS) toxicity. CNS toxicity was dose-limiting; other toxicities were problematic, ie, dose-dependent but not truly dose-limiting. The maximal tolerated dose of thiotepa is 900 to 1,125 mg/m2, with the lower dose being the maximal dose for evaluation in combination chemotherapy. In high-dose phase I evaluation, the overall response rate was approximately 50% with responses seen in a wide variety of solid tumors, lymphomas, and pediatric tumors. High-dose thiotepa appears to be an alkylating agent with broad-spectrum antitumor efficacy, which should add to the cytoreductive regimens for both solid and hematopoietic tumors.
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PMID:High-dose N,N',N"-triethylenethiophosphoramide (thiotepa) with autologous bone marrow transplantation: phase I studies. 210 65

Treatment options for patients with ovarian cancer who have failed systemic and intraperitoneal (ip) cisplatin-based chemotherapy are limited. We conducted a phase I clinical study of ip thiotepa in patients with refractory ovarian cancer to determine the maximum tolerated dose (MTD). Ten patients were given 39 courses of thiotepa (median number of courses per patient, 3.5; range, 1-10+). All patients had received prior ip cisplatin; 7 also had received iv cisplatin, and 5 had three or more prior regimens. Thiotepa (30-80 mg/m2) was given ip in 2 liters normal saline every 4 weeks. The therapy was well tolerated. There was no vomiting, stomatitis, alopecia, or peritonitis. The dose-limiting toxicity was myelosuppression. With repeated doses, patients had a delayed marrow recovery and required a 1- to 2-week delay in treatment. Six patients had stable disease (duration 2-14+ months; median duration 5 months); 1 patient had a 50% decrease in CA-125 level, and 1 patient with no measurable disease remained clinically disease-free. In summary, ip thiotepa had clinical activity in heavily pretreated patients with refractory ovarian cancer with disease stabilization seen in 6 of 9 evaluable patients and a partial response seen in 1 patient. Myelosuppression was the only toxicity encountered. A dose of 60 mg/m2 ip is recommended for phase II studies.
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PMID:A phase I clinical trial of intraperitoneal thiotepa for refractory ovarian cancer. 210 79

Thiotepa is a common alkylating agent known to precipitate cutaneous reactions consistent with toxic erythema of chemotherapy, including erythema and hyperpigmentation. Herein, we describe an atypical case of malignant intertrigo involving preferential erythema and desquamation not only of skin folds but also of occluded areas after thiotepa-based conditioning. The diagnosis was complicated by concurrent stomatitis and oral petechiae in the setting of autologous stem cell transplant 11 days prior for diffuse large B-cell lymphoma. Histopathological examination from two cutaneous sites demonstrated epidermal dysmaturation and eccrine gland necrosis consistent with thiotepa-induced desquamation and not Stevens-Johnson syndrome or graft-versus-host-disease. Malignant intertrigo can present with extensive cutaneous involvement, as evidenced by our patient who had 25% body surface area affected. Mucosal involvement is common with most chemotherapeutic regimens and its presence should not deter the astute clinician from consideration of a diagnosis of toxic erythema of chemotherapy. No further interventions were needed and the patient healed spontaneously.
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PMID:Thiotepa hyperpigmentation preceding epidermal necrosis: malignant intertrigo misdiagnosed as Stevens-Johnson syndrome-toxic epidermal necrolysis overlap. 3223 90