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)

4'-Epidoxorubicin (epi-DXR) was tested in 56 patients with various types of advanced malignancies. The pattern of acute toxicity was similar to that of doxorubicin (DXR), but epi-DXR produced a lower incidence of vomiting, stomatitis, alopecia, and myelosuppression. The study of cardiac toxicity, utilizing only noninvasive methods, indicated that epi-DXR also is cardiotoxic. The increase in the systolic time intervals after the first dose as well as after cumulative doses was slightly lower compared with that observed after DXR. Antitumor activity occurred in a variety of tumors including malignant melanoma, renal cancer, and rectal cancer, which are refractory to DXR. Present results suggest that further studies with epi-DXR are indicated.
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PMID:Preliminary clinical experience with 4-epidoxorubicin in advanced human neoplasia. 693 64

A Phase I-II study with 4'-epi-doxorubicin (epi-DX) was performed in 108 patients with various types of advanced malignancy. The pattern of acute toxicity was similar to that of doxorubicin (DX). However, epi-DX was better tolerated than DX because of comparative lower incidence of vomiting, stomatitis, complete alopecia and severe myelosuppression. Cardiac toxicity was studied by utilizing noninvasive methods, and the electrocardiographic results suggested a slightly lower cardiac damage after epi-DX compared to DX. Antitumor activity was documented in a variety of neoplasms, and objective response was also observed in those considered refractory to DX such as malignant melanoma and renal cancer. X
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PMID:Toxic and therapeutic activity of 4'-epi-doxorubicin. 695 68

A Phase I dose escalation trial of i.v. administered recombinant human interleukin 12 (rhIL-12) was performed to determine its toxicity, maximum tolerated dose (MTD), pharmacokinetics, and biological and potential antineoplastic effects. Cohorts of four to six patients with advanced cancer, Karnofsky performance >/=70%, and normal organ function received escalating doses (3-1000 ng/kg/day) of rhIL-12 (Genetics Institute, Inc.) by bolus i.v. injection once as an inpatient and then, after a 2-week rest period, once daily for five days every 3 weeks as an outpatient. Therapy was withheld for grade 3 toxicity (grade 4 hyperbilirubinemia or neutropenia), and dose escalation was halted if three of six patients experienced a dose-limiting toxicity (DLT). After establishment of the MTD, eight more patients were enrolled to further assess the safety, pharmacokinetics, and immunobiology of this dose. Forty patients were enrolled, including 20 with renal cancer, 12 with melanoma, and 5 with colon cancer; 25 patients had received prior systemic therapy. Common toxicities included fever/chills, fatigue, nausea, vomiting, and headache. Fever was first observed at the 3 ng/kg dose level, typically occurred 8-12 h after rhIL-12 administration, and was incompletely suppressed with nonsteroidal anti-inflammatory drugs. Routine laboratory changes included anemia, neutropenia, lymphopenia, hyperglycemia, thrombocytopenia, and hypoalbuminemia. DLTs included oral stomatitis and liver function test abnormalities, predominantly elevated transaminases, which occurred in three of four patients at the 1000 ng/kg dose level. The 500 ng/kg dose level was determined to be the MTD. This dose, administered by this schedule, was associated with asymptomatic hepatic function test abnormalities in three patients and an onstudy death due to Clostridia perfringens septicemia but was otherwise well tolerated by the 14 patients treated in the dose escalation and safety phases. The T1/2 elimination of rhIL-12 was calculated to be 5.3-9.6 h. Biological effects included dose-dependent increases in circulating IFN-gamma, which exhibited attenuation with subsequent cycles. Serum neopterin rose in a reproducible fashion regardless of dose or cycle. Tumor necrosis factor alpha was not detected by ELISA. One of 40 patients developed a low titer antibody to rhIL-12. Lymphopenia was observed at all dose levels, with recovery occurring within several days of completing treatment without rebound lymphocytosis. There was one partial response (renal cell cancer) and one transient complete response (melanoma), both in previously untreated patients. Four additional patients received all proposed treatment without disease progression. rhIL-12 administered according to this schedule is biologically and clinically active at doses tolerable by most patients in an outpatient setting. Nonetheless, additional Phase I studies examining different schedules and the mechanisms of the specific DLTs are indicated before proceeding to Phase II testing.
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PMID:Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. 981 99