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)

13 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and 7 patients with acute myeloid leukemia (AML) were treated with a regimen that included idarubicin 12 mg/m2 intravenously daily for 3 d plus cytarabine 2 g/m2 by infusion over 3 hours daily for 3 d. There were 10 remissions (ALL:7; AML:3) in the 15 relapsed patients and 4 (ALL:3) in the 5 patients with primary refractory disease. Severe myelosuppression was observed in all patients. Toxicity of this regimen caused nausea and vomiting, stomatitis, infections and/or liver enzymes increase. Cardiac toxicity was not observed. 2 patients died in aplasia of Gram-negative septicemia and brain hemorrhage. In conclusion, the combination of idarubicin and intermediate-dose cytarabine (IDARA-C) seems to be highly effective and sufficiently well-tolerated for the treatment of refractory and relapsed acute leukemias.
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PMID:Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias. 258 57

A clinical study was designed to evaluate the tolerance of cancer patients to liposome-associated doxorubicin (L-DXR). The liposomes used contain phosphatidylglycerol, phosphatidylcholine, cholesterol, and DXR intercalated in the lipid bilayer, and have a mean size in the range of 0.3-0.5 microns. Thirty-two patients, most of them with primary or metastatic liver cancer refractory to conventional therapy, were entered into the study. A total of 69 courses of therapy was administered by intravenous infusion of a suspension of L-DXR (0.5-2.0 mg DXR/ml) in physiologic saline at an approximate rate of 2 ml/min given on a 3-week intermittent schedule. The L-DXR and phospholipid doses were escalated from 20 mg/m2 and 0.3 g/m2 to 120 mg/m2 and 3.2 g/m2 respectively. Treatment was generally well tolerated and acute toxic effects such as nausea and vomiting were mild and infrequent. Chills and fever (greater than 38.0 degrees C) were observed in three patients during infusion of L-DXR and in seven patients 6-12 h after the end of infusion. Median WBC nadir counts were 2700, 2300 and 700/microliters at 85, 100 and 120 mg/m2 respectively. All three patients receiving 120 mg/m2 developed grade 4 leukopenia and fever requiring intravenous antibiotics, and, in two of them, severe stomatitis (grades 3 and 4) was observed. Significant hair loss was apparent in all patients receiving doses higher than 50 mg/m2. The maximal tolerated dose of L-DXR appears to be 120 mg/m2, with leukopenia and stomatitis being the dose-limiting factors. While the subacute toxicity of L-DXR appears to be qualitatively similar to that of free DXR, its tolerance exceeds the recommended dose of free DXR (75 mg/m2) in the standard 3-weekly schedule.
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PMID:Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study. 263 61

In a prospective randomized trial, the pending question was addressed whether Cytosine arabinoside (Ara-C) should be applied at high or intermediate dose to patients with relapsed or refractory acute myeloid leukemia. Based upon the previously established regimen of the sequential application of Ara-C and Mitoxantrone (S-HAM) patients below 60 years of age were randomized to receive Ara-C at either 3.0 g/m2 vs 1.0 g/m2 per dose while older patients were randomly assigned to either 1.0 g/m2 or 0.5 g/m2 Ara-C. At the present early stage 51 patients have entered the study and 37 are currently evaluable for response and toxicity. Complete remissions were achieved in 14 of 28 patients below 60 years of age and in 3 of 8 older cases. Predominant side effects consisted of nausea and vomiting, diarrhea and stomatitis. Further recruitment of patients and longer follow-up is required for the assessment of the various treatment arms.
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PMID:Age related randomized comparison of sequentially applied high-dose versus intermediate dose cytosine arabinoside in combination with mitoxantrone (S-HAM) in the treatment of relapsed and refractory acute myeloid leukemia: study design and preliminary results. 265 90

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.
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PMID:Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. 278 91

We evaluated the role of gallium nitrate infusion in the treatment of metastatic breast cancer. Gallium nitrate was administered at 300 mg/m2/day for 7 days every 3 weeks by continuous infusion concomitantly with oral calcium supplement of 500 mg twice daily and oral hydration. Fifteen patients with refractory metastatic breast cancer received such treatment for a total of 30 courses. Median age was 51, and median performance status (Zubrod scale) was 1. These patients had minimal prior chemotherapy (median 1 regimen). All patients were evaluable for toxicity and 14 for response. Nine patients had one to two metastatic sites, five patients had three to four sites. No major objective response was seen, but one patient had a minor response (10 weeks), and another showed no change in disease (16 weeks). Diverse low-grade toxicities were observed, including nausea and vomiting in 11 patients, anorexia in 11, diarrhea in eight, stomatitis in five, dysgeusia in six, musculoskeletal pain in five, skin rash in seven, partially reversible tinnitus and/or mild hearing loss in four and sensory neuropathy in two. A consistent drop in hemoglobin (median of 3.2 g/dL per patient) necessitated blood transfusion in seven patients. There was no granulocytopenia or thrombocytopenia; however, significant lymphopenia was noted. Reversible, moderate nephrotoxicity occurred in two patients. The hypocalcemic effect was consistent, with a median drop in serum calcium of 1.25 mg/dL per course. There was no hepatic toxicity. While no single toxicity was severe, overall toxicity adversely influenced treatment tolerance. Gallium nitrate by continuous infusion, as given in this study, has no activity in metastatic breast cancer.
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PMID:Phase II evaluation of gallium nitrate by continuous infusion in breast cancer. 279 77

Taxol is a unique plant product that promotes in vitro assembly of microtubules. In a phase I trial, adults with advanced solid tumors were given taxol (formulated with cremophor EL and dehydrated alcohol) as a 3-hour iv infusion every 21 days. The total dose administered ranged from 15 to 230 mg/m2 in nine escalation steps. Leukopenia, thrombocytopenia, nausea and vomiting, alopecia, stomatitis, transient rashes, increases in serum triglyceride levels, and hypersensitivity reactions were observed. Hypersensitivity reactions characterized by acute dyspnea, generalized erythema, and hypotension immediately following the initiation of the taxol infusion occurred in three of five patients receiving greater than or equal to 190 mg/m2 (18% of patients overall). No antitumor activity was observed. Hypersensitivity reactions constituted a treatment-limiting toxicity for this preparation of taxol given on this schedule over the dosage range examined. With the severity and unpredictability of the hypersensitivity reactions, further usage of taxol is not indicated with this drug formulation on this administration schedule. Further studies are warranted to uncover ways to permit the safe administration of taxol.
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PMID:Phase I trial of taxol given as a 3-hour infusion every 21 days. 287 28

Twenty-seven patients with advanced malignancies confined to the head and neck region were treated with intra-arterial (IA) cisplatin and 5-fluorodeoxyuridine (FUDR) using implantable pumps or injection ports. Tumor histologies were: 16 squamous cell, one mucoepidermoid, one adenocarcinoma, one neuroendocrine, four adenoid cystic, two acinic cell, one fibrosarcoma, and one melanoma. All primaries originated from tissues in the head and neck area. Nineteen patients had received prior treatment, including chemotherapy in 13; eight were newly diagnosed. Responses in 26 evaluable patients were two complete (CR), ten partial (PR), six minor (MR), and eight progressions. The median duration of response was 5 months, with a range of 2 to 11 months. Sites of progression were within the infused volume in 13 patients and to uninfused local-regional or distant sites in eight. The response rate in the subset of 15 patients with squamous cell head and neck cancer was 47%. Toxicity in the 26 patients included stomatitis in 88%, nausea and vomiting in 64%, myelosuppression in 15%, and grade 1 nephrotoxicity in 1%. A regional advantage for IA cisplatin and FUDR can be calculated based on total body clearance rates (CLTB) for these agents and estimates of external carotid artery (ECA) blood flow. However, frequent progression of disease outside the infused volume to regional and distant sites limits the usefulness of this approach in recurrent disease patients.
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PMID:Intra-arterial cisplatin and FUDR in advanced malignancies confined to the head and neck. 295 5

Trimetrexate (TMQ; NSC 352122) is a potent inhibitor of dihydrofolate reductase with good activity against murine i.p.-implanted B16 melanoma and colon 26 tumors. Preclinical antineoplastic activity, demonstrated schedule dependency, and data suggesting effectiveness against methotrexate-resistant cells prompted a Phase I clinical and pharmacokinetic study of trimetrexate using an i.v. daily x5 schedule. Forty-three good performance status patients were treated with 12 dose levels using daily doses varying from 0.5 to 15 mg/m2/d. Plasma and urine samples were obtained for pharmacokinetic analysis using a high-performance liquid chromatographic method. Myelosuppression was dose limiting and 15 mg/m2/d x5 was the maximum tolerated dose. White blood cell (WBC) and platelet toxicity were noted at doses of 1.6 mg/m2 and above. Median WBC and platelet nadirs occurred on approximately Days 11-12 with recovery by Days 15-18. Nonhematological toxicity included mucositis, nausea and vomiting, stomatitis, diarrhea, and rash. Evidence for antitumor activity was seen in seven patients. Trimetrexate elimination from plasma could be represented as either a bi- or triexponential process. Terminal elimination half-lives were in the range of 5-14 h in patients represented by a triexponential model. Approximately 10-20% of the dose administered was excreted in urine over a 24-h period. The recommended starting dose for patients in Phase II trials using the d x5 i.v. schedule is 8.0 mg/m2/d repeated every 21 days. Dose escalations may be possible depending on the extent of prior therapy and individual tolerance of the drug.
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PMID:Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule. 297 Feb 94

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of mitoxantrone are reviewed. Mitoxantrone, an aminoanthraquinone that was synthesized in 1979, belongs to a new chemical class of agents known as the anthracenediones. It possesses antiviral, antibacterial, immunomodulatory, and antitumor activity. The drug's antitumor activity is attributed to its interaction with DNA topoisomerase II, and its interaction with human cells may also involve nonintercalary, electrostatic interactions. Mitoxantrone is poorly absorbed orally and is most commonly administered intravenously. The drug is rapidly distributed into the red blood cells, white blood cells, and platelets, followed by deep-tissue sequestration. Mitoxantrone has demonstrated clinical efficacy in the treatment of leukemia, lymphoma, and breast cancer. As a single agent, mitoxantrone has a response rate of roughly 30% in acute nonlymphocytic leukemia or acute myeloid leukemia. In combination with other standard agents (cytarabine, vincristine, and prednisone), the response rate may reach 60%. In breast cancer, mitoxantrone's response rate as a single agent is 25-30%, while combination regimens produce response rates of 60% or more. The drug can cause cardiotoxicity with cumulative doses. Other adverse effects include myelosuppression, nausea and vomiting, stomatitis, mucositis, and alopecia. The cost of mitoxantrone is comparable to that of doxorubicin, but it is substantially more expensive than daunorubicin. Mitoxantrone is an important new agent with antitumor activity in leukemia, lymphoma, and breast cancer. In most situations, mitoxantrone will be considered second-line treatment or a restricted-use item because of its high cost and because of the lack of FDA approval for indications other than acute nonlymphocytic leukemia.
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PMID:Mitoxantrone: a novel anthracycline derivative. 304 48

Three hundred thirty-one women with metastatic breast cancer were randomized to receive combination chemotherapy with either cyclophosphamide, Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ), and fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and fluorouracil (CAF). Patients could not have had prior chemotherapy, although adjuvant chemotherapy was acceptable. Initial doses were 500 mg/m2 of cyclophosphamide and 500 mg/m2 of fluorouracil with either 10 mg/m2 of mitoxantrone or 50 mg/m2 of doxorubicin, administered intravenously (IV) on day 1 and repeated every 3 weeks. There were no statistically significant differences in pretreatment or prior therapy characteristics between the groups. For patients assigned to the CNF and CAF groups, respectively, 25 (18%) were premenopausal, 39 (40%) were estrogen receptor (ER) negative, 39 (38%) had a disease-free interval less than 1 year, and 24 (26%) had received prior adjuvant chemotherapy. All patients were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. None of these parameters were statistically significant favoring one regimen over the other. The response rate (complete [CR] and partial response [PR]) was 29% for the CNF group (95% confidence interval of 22% to 37%) and 37% for the CAF group (95% confidence interval of 29% to 45%). The median response duration and TTF were 171 days and 125 days for the CNF group and 254 days and 147 days for the CAF group, respectively. The median survival times for the CNF group and the CAF group were 377 and 385 days, respectively. The major dose-limiting toxicity for both regimens was leukopenia, manifested as granulocytopenia. The incidence of stomatitis/mucositis was 10% in the CNF group and 19% in the CAF group. Alopecia occurred in 49% of CNF patients (severely for 4%) and in 86% of CAF patients (severely for 39%). Nausea/vomiting occurred in 80% of CNF patients and in 81% of CAF patients; the degree of severity was also comparable. There was significantly less cardiotoxicity observed in the CNF group compared with the CAF group. Although CNF is somewhat less effective in overall response rate, survival curves are identical. CNF can be offered to patients who reject anthracycline-containing regimens because of fear of alopecia.
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PMID:A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma. 304 53


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