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)

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was investigated for its clinical efficacy in the treatment of various types of neutropenia (3 cases with idiopathic neutropenia of suspected drug induction, 5 cases with idiopathic neutropenia of other origin, and 2 cases with cyclic neutropenia). Treatment with glycosylated rhG-CSF produced in the Chinese Hamster Ovary cells at dose levels of 2-5 micrograms/kg/day caused rapid increases of neutrophil counts associated with an improvement of the infection. In cyclic neutropenia patients, marked reduction in the duration of the neutropenic period was observed with rhG-CSF administration started before the period. Intercurrent stomatitis, which occurred in 1 patient, was markedly milder as compared to a previous episode which occurred during an untreated neutropenic period. The treatment of rhG-CSF was well tolerated and no adverse events were observed, nor was there any detectable anti-rhG-CSF antibody in any patients studied; hence the clinical use of rhG-CSF is considered to be safe. These results suggest beneficial effects of rhG-CSF on the recovery of neutrophil counts in cyclic and other types of idiopathic neutropenias, as well as for the treatment of neutropenia-associated infection.
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PMID:Clinical effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on various types of neutropenia including cyclic neutropenia. 172 91

50 women with advanced breast cancer were treated with an intensified regimen which consisted of high-dose epirubicin (110 mg/m2) every 2 weeks and filgrastim (5 micrograms/kg) subcutaneously for 13 days, starting 24 h after chemotherapy. 44 patients completed all six cycles. The median interval between cycles of treatment was 14.3 days. The actually administered median dose per unit time per patient was 53 mg/m2/week, amounting to 97.2% of the dose prescribed by the protocol. 7 [14%, 95% confidence interval (C.I.) 4-24%] patients achieved a complete and 25 (50%, 95% C.I. 36-64%) a partial response. Median time to progression was 32 weeks and median survival 64 weeks. Stomatitis and fever each occurred in 7 (14%) patients. Grade 3 haematological toxicity was observed in 6 (12%) patients. 1 (2%) patient developed grade 4 cardiac toxicity. This intensified regimen appears to be a well tolerated and effective treatment in advanced breast cancer.
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PMID:Intensive chemotherapy with high-dose epirubicin every 2 weeks and prophylactic administration of filgrastim in advanced breast cancer. 752 79

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 250 mg/m2 by 24-hour infusion at 21-day intervals was evaluated at M.D. Anderson Cancer Center as a single agent in patients who had received one prior chemotherapy regimen either as adjuvant therapy or for metastatic disease. Of 25 patients treated, 12% had a complete remission and 44% had a partial response. The median time to progression was 9 months (range, 1 to 20 months). In the next phase of development, a phase I trial evaluated sequentially administered paclitaxel and doxorubicin as initial therapy for metastatic disease. Granulocyte colony-stimulating factor also was administered in each cycle. The dose-limiting toxicity was either stomatitis or neutropenic fever. The maximum tolerated dose (MTD) was 125 mg/m2 for paclitaxel and 48 mg/m2 for doxorubicin. Because of much lower than anticipated MTDs of both drugs in this schedule, it was hypothesized that there may be a schedule-dependent toxicity; therefore, in the second phase I study the schedule of administration was reversed (ie, doxorubicin followed by paclitaxel infusion). The MTDs of this schedule were 60 mg/m2 and 150 mg/m2 for doxorubicin and paclitaxel, respectively. Pharmacokinetic studies subsequently have confirmed that administration of paclitaxel before doxorubicin impairs the elimination of doxorubicin by some unknown mechanism. In an ongoing phase II study, paclitaxel is being evaluated in patients who have received three or more treatments with chemotherapy. Paclitaxel is administered at doses of 135 and 150 mg/m2 (for poor- and good-risk patients, respectively) without granulocyte colony-stimulating factor. Six patients (19%) have shown objective partial responses. Our initial phase II study showed significant antitumor activity for paclitaxel in patients who had received limited prior chemotherapy. Our phase I studies established that initial administration of paclitaxel alters the pharmacokinetics of doxorubicin and increases morbidity. The reverse sequence of administration was associated with better tolerance and a higher MTD. In heavily treated patients this drug also has significant antitumor activity.
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PMID:Paclitaxel in the treatment of metastatic breast cancer: M.D. Anderson Cancer Center experience. 754 Nov 51

Recent attempts to reduce weight by patients with anorexia nervosa have sometimes led to life-threatening hematologic complications. This report describes an instance in which a patient with anorexia nervosa and pancytopenia drastically improved with treatment that included administration of granulocyte colony-stimulating factor. The patient had lost 27 kg of body weight within 8 months. Even after admission, the blood cell count continued to decrease rapidly as follows: platelet, from 244 x 10(3)/microliters to 44 x 10(3)/microliters; erythrocyte, from 4.04 x 10(6)/microliters to 2.58 x 10(6)/microliters; and leukocyte, from 4.8 x 10(3)/microliters to 1.6 x 10(3)/microliters (granulocyte, 0.8 x 10(3)/microliters). Complications included pneumomediastinum, pneumothorax, purpura, petechiae, hepatomegaly, fever, gangrenous stomatitis, and somnolence. Bone marrow aspiration disclosed absence of fat cells, marrow hypoplasia, and infiltration of the mature lymphocytes. Intravenous hyperalimentation, blood transfusion, gamma-globulin, and antibiotics were administered, but leukopenia and fever remained. However, administration of recombinant human granulocyte colony-stimulating factor dramatically reversed the leukopenia and fever. With careful nutrition therapy, the patient's blood cell count and bone marrow normalized by the time of discharge. It was concluded that severe hematologic disorders may occur in patients with anorexia nervosa, and advanced treatment may be required to save the patient's life.
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PMID:Case report: reversal of severe leukopenia by granulocyte colony-stimulating factor in anorexia nervosa. 768 51

We determined the effective method of administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with transitional cell carcinoma of the urothelium receiving methotrexate, etoposide and cisplatinum (MEC) therapy. Recombinant human G-CSF was administered at 2 micrograms/kg subcutaneously starting after the white blood cell count was less than 3,000/mm3 (short administration) or starting immediately after finishing MEC therapy (prophylactic administration). The median white blood cell nadir for the control group, short administration group and prophylactic administration group, was 275 +/- 77, 250 +/- 317 and 2,066 +/- 47/mm3, respectively. The number of days with a white blood count of less than 1,000/mm3 for the control group, short administration group and prophylactic administration group was 6.6 +/- 0.6, 4 +/- 2 and 0.9 +/- 0.5 days, respectively. The difference between the control group and prophylactic administration group was statistically significant (p < 0.01). These findings indicated that the prophylactic administration of rhG-CSF following MEC therapy was effective for preventing leukopenia. Other side effects of stomatitis, diarrhea and pneumonia were also decreased using rhG-CSF after MEC therapy.
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PMID:[Effect of recombinant human granulocyte colony stimulating factor in patients with transitional cell carcinoma of the urothelium receiving methotrexate, etoposide and cisplatinum combination chemotherapy]. 768 38

Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed. In vitro studies using 3H-thymidine uptake and dual parameter flow-cytometric analysis of DNA and proliferating cell nuclear antigen showed that leukemic blast cells in S phase were increased after incubation with G-CSF. G-CSF also enhanced expression of the transferrin receptor (CD71) on blast cells in vitro. These observations suggest that G-CSF/Ara-C therapy may be useful in the treatment of high-risk AML.
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PMID:Recombinant human granulocyte colony-stimulating factor in combination with continuous infusion of cytosine arabinoside for the treatment of refractory acute myelogenous leukemia. 768 79

In three phase I trials reported in the United States, the combination of paclitaxel and doxorubicin has been evaluated in previously untreated patients with metastic breast cancer. At M.D. Anderson Cancer Center, escalating doses of paclitaxel followed by a fixed dose of doxorubicin led to one complete remission (CR) and seven partial remissions (PRs) in 10 patients. Dose-limiting toxic effects were stomatitis and neutropenic fever. The maximum tolerated dose (MTD) was paclitaxel 125 mg/m2 and doxorubicin 48 mg/m2-lower than the starting dose. The reverse sequence (doxorubicin followed by paclitaxel) also was investigated to evaluate the possibility of schedule-dependent toxicity. The MTD of this reverse sequence was doxorubicin 60 mg/m2 and paclitaxel 150 mg/m2, with neutropenic fever as the dose-limiting toxicity. In a study by the National Cancer Institute (NCI), paclitaxel and doxorubicin were given simultaneously over 72 hours and doses of each were escalated resulting in two separate MTDs: paclitaxel/doxorubicin 160/75 and 180/60 mg/m2. Objective responses were 6% CR and 56% PR, and gastrointestinal disturbances were dose-limiting. Schedule-dependence also was addressed in a study at Indiana University, where the drug sequence was alternated for comparison both between and across patients. Preliminary results showed an increase in mucositis when paclitaxel was given before doxorubicin. It is concluded that this is an active combination and that schedule-dependent mucositis can be avoided if doxorubicin is given first. Myelosuppression is dose-limiting, even with granulocyte colony-stimulating factor, and thrombocytopenia occurs with multiple courses.
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PMID:Combination chemotherapy with Taxol (paclitaxel) in metastatic breast cancer. 786 29

Cyclic neutropenia is a stem-cell disorder characterized by regular 21-day cyclic fluctuations in the number of neutrophils in the blood and bone marrow. The neutropenic periods may be complicated by fever, stomatitis and severe infections. In this case report only daily continuous and later intermittent treatment with recombinant human granulocyte colony-stimulating factor (two micrograms/kg) administered subcutaneously effectively prevented recurrent infections.
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PMID:[rhG-CSF treatment in cyclic neutropenia. Continuous versus intermittent rhG-CSF treatment in cyclic neutropenia]. 829 27

A combination of platinum and a taxane is regarded by many as the optimum treatment for advanced epithelial ovarian carcinoma. A recent meta-analysis has suggested that the addition of an anthracycline to platinum-based chemotherapy is associated with a significant survival advantage. We are therefore conducting an ongoing phase I/II study combining drugs from these three classes. We report here the first phase using carboplatin at an area under the concentration-time curve of 7, doxorubicin 50 mg/m2, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 over 3 hours. The treatment was given on a 3-weekly cycle and granulocyte colony-stimulating factor was given if the nadir neutrophil count fell below 0.5 x 10(9)/L and was continued until recovery. Toxicity was assessed according to the Common Toxicity Criteria. All patients were required to have advanced ovarian cancer (stage IC to IV) but be ineligible for standard chemotherapy trials or to have advanced gynecologic malignancy, such as mixed mullerian tumor, fallopian tube carcinoma, coelomic carcinoma, or primary peritoneal carcinoma. To date, seven patients have been treated, and all were of performance status 0 to 2, 18 to 70 years old, with a life expectancy of > or = 3 months. Hematologic toxicity was significant, with all patients having grade 3/4 thrombocytopenia and six of seven grade 3/4 leukopenia. There was, however, only one grade 3/4 infection. Three patients have experienced fatigue, which in two cases was severe, and one patient had grade 3/4 stomatitis. Dose reduction was due to myelosuppression and was required in five patients. Five patients were evaluable for response, all of whom have obtained complete or partial response. There has been no clinical evidence of cardiotoxicity, but four patients had grade 1/2 cardiotoxicity as measured by left ventricular ejection fraction. We conclude that this combination is active and has acceptable but significant toxicity. It is only suitable for very fit patients, and we are currently assessing ways of reducing toxicity.
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PMID:Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. 904 34

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be one of the most active drugs in the treatment of advanced head and neck cancer. The maximum tolerated dose of paclitaxel in combination with carboplatin is currently being evaluated in phase I/II studies. We designed a phase II study to evaluate the activity and acute and cumulative toxicity of this combination in patients with recurrent or metastatic cancer of the head and neck. Chemotherapy consisted of paclitaxel 200 mg/m2, given as a 3-hour infusion, and carboplatin dosed to an area under the concentration-time curve of 7 mg x min/mL, administered every 28 days. Granulocyte colony-stimulating factor (5 microg/kg) also was given on days 2 to 12 of each cycle. At the time of this report, 41 patients had entered this study. Primary sites included the nasopharynx (10 patients), larynx (18), oral cavity (three), oropharynx (six), hypopharynx (three), and unknown (one). Among 25 evaluable patients with non-nasopharyngeal cancer, there were two complete responses and three partial responses, for an overall response rate of 20% (95% confidence interval, 4% to 36%). Among eight evaluable patients with nasopharyngeal cancer, four achieved a complete response and two a partial response. Grade 3 to 4 toxicities included anemia (2.5%), leukopenia (7.5%), thrombocytopenia (5%), vomiting (5%), stomatitis (2.5%), and infection (5%). These preliminary data indicate that the combination of paclitaxel and carboplatin is active against advanced head and neck cancer, particularly when used in the treatment of nasopharyngeal cancer.
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PMID:Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. 904 40


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