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)

It is unusual to obtain responses after two different sequential regimens in patients with metastatic breast cancer. In this retrospective analysis, data were examined on 22 patients who had already received two or three different regimens for metastatic breast cancer before being treated with 100 mg/m2 docetaxel (or 75 mg/m2 if clinically warranted). 13 patients received three or more courses and 21 patients were assessable for response. 5 of 21 assessable patients (24%) responded for 3-11 months and a further 6 (29%) stabilised. Toxicity (WHO grade 3 and/or 4), principally neutropenia, stomatitis and fluid retention, occurred in 10 patients. We conclude that docetaxel is an active agent in heavily pretreated patients with metastatic breast cancer, but care should be taken to minimise side-effects in this group of patients.
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PMID:Docetaxel: response in patients who have received at least two prior chemotherapy regimens for metastatic breast cancer. 979 91

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels </=150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to <5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count <500/microliter) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets <20,000/microliter) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose-limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1-4, with cyclophosphamide 4. 2 g/m2 on day 5 and G-CSF 5 microgram/kg/day started on day 6 and administered until the total WBC is above 10,000/microliter for three consecutive days.
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PMID:High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support. 981 32

Doxorubicin and paclitaxel both display strong antitumor activity in the treatment of breast cancer. The optimal schedule of this combination, however, remains undefined. In this phase I and pharmacologic study, we administered weekly 12 mg/m2 doxorubicin as a bolus infusion immediately followed by a 1 h 80 mg/m2 paclitaxel infusion to patients with metastatic breast cancer. A total of 119 weekly courses were delivered to seven patients. Grade IV neutropenia was observed in two patients at the first dose level, thus already defining the maximum tolerated dose. Pronounced non-hematologic toxicities were mild neuropathy (grade I: 39%) and stomatitis (grade I: 19%, grade II: 8%). No signs of cardiac toxicity were observed with this dose schedule. Three partial responses were achieved in this group of heavily pretreated patients. The pharmacokinetics of paclitaxel, doxorubicin and Cremophor EL with this schedule were analyzed. Overall, the schedule was well tolerated and combined with its preliminary response rate justifies further evaluation in phase II studies.
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PMID:Phase I and pharmacologic study of weekly doxorubicin and 1 h infusional paclitaxel in patients with advanced breast cancer. 982 24

Motivated by the observation of preclinical synergy, a Phase I dose escalation study of edatrexate in combination with a 3-h paclitaxel infusion was performed in patients with advanced breast cancer to determine the maximum tolerated dose (MTD) of edatrexate and the toxicities associated with this combination and to report preliminary observations of efficacy with this novel combination. Thirty-six patients were enrolled in this Phase I trial. Thirty-five eligible patients were treated every 21 days in cohorts of at least three patients and were assessable for toxicity. One patient was ineligible due to hyperbilirubinemia. Stepwise dose escalations of edatrexate were administered until grade >3 nonhematological dose-limiting toxicities were reported. The initial dose level of edatrexate was 180 mg/m2; subsequent cohorts were treated with escalating doses of edatrexate (210, 240, 270, 300, 350, and 400 mg/m2). Edatrexate was administered by i.v. infusion over 1 h. Paclitaxel was administered 24 h later at a fixed dose of 175 mg/m2 as a 3-h infusion with standard dexamethasone, diphenhydramine, and cimetidine premedication. The MTD of edatrexate was reached at the 350 mg/m2 level in this study. Grade 3 diarrhea was seen in one patient at the 300 and 400 mg/m2 dose levels, requiring dose reductions. Two patients experienced grade 4 stomatitis at the 400 mg/m2 dose level and also required dose reduction, establishing the MTD as 350 mg/m2. Grade 3 nausea and vomiting were noted in two of three patients at the highest dose level. Of 35 patients, 4 patients reported grade 3 myalgias and 1 patient reported grade 3 neurosensory complaints, which were seen mostly at the 350 and 400 mg/m2 dose levels; however, 1 patient reported grade 3 myalgias at 180 mg/m2. No cumulative neurotoxicity was observed, and no patient experienced an allergic reaction to paclitaxel. In 23 patients with bidimensionally measurable disease, there were four complete (17%) and seven partial responses, with an overall response rate of 48% (95% confidence interval, 27-69%). All of the responses were seen in patients who had not received prior chemotherapy for stage IV disease. The median duration of response was not assessable because many responding patients went on to receive high-dose chemotherapy treatment with stem cell support. The combination of edatrexate and paclitaxel for treatment of metastatic breast cancer is a feasible and safe regimen. The MTD of edatrexate was 350 mg/m2 when combined with a 3-h infusion of paclitaxel (175 mg/m2) given 24 h later. Activity was noted even among patients who had relapsed shortly after receiving methotrexate- and/or doxorubicin-containing adjuvant regimens. Additional studies evaluating the sequences and dosing schema for this combination are warranted to improve the response proportion and define the duration of the response.
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PMID:Phase I study of escalating doses of edatrexate in combination with paclitaxel in patients with metastatic breast cancer. 1003 75

The purpose of this study was to evaluate the maximum tolerated dose and the toxicity profile of vinorelbine administered by continuous infusion for 96 hours to patients who had received prior chemotherapy for metastatic breast cancer. Forty-three patients with metastatic breast cancer were treated with vinorelbine 8 mg intravenously for 10 minutes (day 1) followed by continuous infusion of vinorelbine for 96 hours. Treatments were repeated every 3 weeks. Eighty-eight percent of the patients had had two or more prior chemotherapeutic regimens: 91% had prior doxorubicin therapy and 77% had prior paclitaxel therapy. All 43 patients were evaluable for toxicity. The median age was 49 years. All patients had a performance status less than or equal to 2 and a life expectancy more than 12 weeks. Eight dose levels were evaluated, and a total of 182 cycles were given. National Cancer Institute grade III or IV granulocytopenia was observed in 64 (35%) cycles, neutropenic fever in 27 (15%) cycles, fatigue (National Cancer Institute grade III or IV) in 18 (10%) cycles, and hand-foot syndrome in 8 (4%) cycles. In 17 (9%) cycles, patients were hospitalized. The maximum tolerated dose of this regimen was determined to be vinorelbine 8 mg intravenously for 10 minutes (day 1) followed by continuous vinorelbine infusion 11 mg/m2 for 96 hours. The dose-limiting toxicity was neutropenic fever and stomatitis.
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PMID:Phase I study of vinorelbine by 96-hour infusion in advanced metastatic breast cancer. 1077 69

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.
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PMID:Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study. 1097 25

BACKGROUND: Chemotherapeutic regimens, such as cyclophosphamide + doxorubicin + 5FU (CAF) or cyclophosphamide + methotrexate + 5FU (CMF), are sometimes used in combination with endocrine or radiotherapy as a standard first line of treatment for recurrent or metastatic breast cancer. However, many cases are, or become, refractory to these treatments. METHODS: Twenty-one women with recurrent or metastatic breast cancer who previously underwent treatment were administered our original regimen of combinationchemotherapy, MFL-P: Day 1, bolus methotrexate (MTX) 50 mg/body (median dose, 33 mg/m(2); range, 29-35 mg/m(2)) and 4 hours later 5-fluorouracil (5FU) 750 mg/body/h (median dose, 497 mg/m(2)/h; range, 441-528 mg/m(2) /h); Days 2-3, bolus leucovorin(LV) 15 mg/body every 8 h x 3; Days 2-5, 72 hours continuous 5FU 750 mg/body/24h; Day 6, cisplatin (CDDP) 50 mg/body/h (median dose, 33 mg/m(2)/h; range, 29-35 mg/m(2) /h) with sufficient hydration. The subjects ranged in age from 26 to 63 years (mean age, 51.3 years). RESULTS: One complete and 9 partial responses were achieved among the 20 patients (response rate, 50%). In 1 patient, diffuse liver metastasis was not measurable. Among various metastatic sites, a higher response rate was observed especially for soft tissue lesions (skin, chest wall and lymph nodes; 9 responders among 11 lesions). On the other hand, in visceral or skeletal metastases, the response rate was poor. The adverse effects were tolerable in all patients, except for common low-grade stomatitis or anorexia. CONCLUSION: MFL-P is useful as a second or third line of therapy for patients with refractory, recurrent or metastatic breast cancer with soft tissues lesions.
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PMID:MFL-P Chemotherapy for Pretreated Metastatic Breast Cancer Patients: A Regimen with Triple Biochemical Modulation by MTX-5FU, LV-5FU and 5FU-CDDP. 1109 14

Vinorelbine (Navelbine) has significant activity against breast carcinoma and is less neurotoxic than vinblastine. Because vinblastine has improved activity when administered by continuous infusion, we conducted a Phase I-II study to determine the maximum tolerated dose (MTD) of vinorelbine when given by continuous infusion and the response rates to it in heavily pretreated metastatic breast cancer patients. Between April 1994 and August 1997, 87 patients were entered in the study. All were female and had proven metastatic breast cancer. Ninety-five percent of them had received prior doxorubicin treatment, and 74% had received prior paclitaxel treatment. In Phase I of the study, all patients received 8 mg of vinorelbine by intravenous (i.v.) bolus followed by a continuous infusion of vinorelbine over 96 hr. When the MTD was determined, patients were entered in the Phase II arm to assess treatment responses and cumulative toxic reactions. In the Phase I arm (43 patients, 182 cycles), we determined the MTD of vinorelbine to be 8 mg by i.v. bolus followed by a continuous infusion of 11 mg/m2/day over 4 days. The dose-limiting toxic reaction was grade 3-4 granulocytopenia in 35% of the cycles and neutropenic fever in 15% of the cycles. Forty-four patients (193 cycles) were treated at the MTD. Seven (16%) of them had a response (2 complete responses, 5 partial responses). The median durations of response and survival were 4.3 and 8.6 months, respectively. However, cumulative toxic reactions (neutropenic fever and stomatitis) in 22 patients (50%) required dose reductions. A continuous infusion of vinorelbine can be safely administered but with a narrow therapeutic index because of cumulative toxic reactions. We recommend a modified MTD of vinorelbine: 8 mg by i.v. bolus followed by a continuous infusion of 10 mg/m2/day over 4 days. However, this treatment schedule offers no apparent advantage over the commonly used weekly vinorelbine schedule.
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PMID:Phase I-II vinorelbine (Navelbine) by continuous infusion in patients with metastatic breast cancer: cumulative toxicities limit dose escalation. 1145 13

The aim of the study was to define a regular and tolerable dose of the epirubicin-docetaxel combination in first-line chemotherapy of patients with metastatic breast cancer. Sixty-five women with measurable and/or evaluable disease were treated with epirubicin escalated from 60 to 110 mg/m(2) according to 5 dose levels, in combination with a fixed dose of 75 mg/m(2) docetaxel, every 21 days for 6 cycles, without preventive use of hematopoietic growth factors or antibiotics. Forty-three women received adjuvant chemotherapy, consisting of anthracyline- or anthracenedione-based regimens in 39 cases (60%). Twenty-seven women were treated in the phase I study (3 at epirubicin 60 mg/m(2), and 6 at each subsequent dose level). Dose-limiting toxicity consisted of grade III asthenia and febrile neutropenia (epirubicin 75 mg/m(2)), grade IV thrombopenia and grade III asthenia (epirubicin 90 mg/m(2)), grade IV stomatitis and grade III diarrhea (epirubicin 100 mg/m(2)), and grade III diarrhea (epirubicin 110 mg/m(2)). In the phase II study, an additional 38 women were treated at epirubicin 90 mg/m(2) and epirubicin 100 mg/m(2). During the 349 cycles delivered, grade IV neutropenia occurred in 90%; febrile neutropenia requiring hospitalization occurred in 62 (17.8%) and lasted more than 3 days in 12 (3.4%). Nonhematologic toxicity was acceptable. Three left ventricular ejection fraction depressions occurred and normalized during follow-up. The overall response rate in the 62 evaluable women was 69.4% (range: 58--81%), with a median duration of 7.8 months. After 26 months of follow-up, the median time to progression was 9.1 months and median overall survival was 22.7 months. On the basis of efficacy and toxicity, the recommended dose of the combination is epirubicin 100 mg/m(2) plus docetaxel 75 mg/m(2).
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PMID:Epirubicin--docetaxel combination in first-line chemotherapy for patients with metastatic breast cancer: final results of a dose-finding and efficacy study. 1147 55

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.
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PMID:An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes. 1193 10


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