Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty patients with relapsed (26) or refractory (14) myeloma were treated with epirubicin of doses of 75, 90, 105, and 120 mg/m2 in groups of 6 or more patients to test for response, maximum tolerated dose, and toxicity. Thirteen patients had received prior doxorubicin and were included in the dose findings part of the study only. Staging was I (1), II (5), and III (34). Partial responses were seen in 5 patients (18.5%) (duration 1.5, 2, 2.5, 10, and 18 months) not previously treated with doxorubicin. No responses were seen in patients treated with prior anthracycline. Responses were not dependent upon dose level of epirubicin. Median nadir white blood cell count at the four-dose levels were 2,300, 1,000, 1,600, and 1,700/mm3 with median nadir granulocyte counts of 897, 720, 688, and 192/mm3. Fever/neutropenia was infrequently observed at the three lower dose levels but occurred in 6 of 10 patients at 120 mg/m2. Platelet nadirs were 110,000, 83,000, 169,000, and 42,000/mm3. Nonhematological toxicity was not dose dependent and included alopecia (100%), nausea/vomiting (40%), and stomatitis (25%). Six patients had greater than or equal to 0.10 changes in the resting ejection fraction with one patient developing congestive heart failure that responded to medical management. This patient had received prior doxorubicin and had a history of myocardial infarction. Epirubicin can produce remissions in patients with previously treated myeloma who have not received prior doxorubicin. Since the response rate was not enhanced at 120/m2 and since fever/neutropenia was seen regularly at this dose level, the recommended dose for further study is 105 mg/m2.
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PMID:Phase I-II study of epirubicin in multiple myeloma. 316 70

A 74-year-old woman with refractory congestive heart failure due to long-standing calcific mitral stenosis who refused surgical intervention was treated with percutaneous balloon valvuloplasty. After an uneventful procedure, hemodynamic results were satisfactory with an increase in the mitral valve area from 0.4 to 1.1 cm2. Five hours after the procedure, the patient had a bout of vomiting followed by pulmonary aspiration. Electrocardiography, and in the further course, creatine kinase MB elevation, showed anterior myocardial infarction. Necropsy disclosed embolic material in the mid left anterior descending artery which unequivocally consisted of valvular material. This case demonstrates embolism of valvular debris as a life-threatening, procedure-related complication of percutaneous valvuloplasty of calcific mitral stenosis.
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PMID:Coronary arterial embolism due to valvular debris after percutaneous valvuloplasty of calcific mitral stenosis. 323 8

Propafenone, an anti-arrhythmic medication recently introduced in class lc, was tested in a multicentric open study including 3,687 patients (mean age: 60 years), presenting a supra ventricular (n = 2,146, 59 p. cent), nodal (n = 351, 10 p. cent) or ventricular (n = 1,613, 44 p. cent) arrhythmia, in order to study its efficacy and tolerance. After exclusion of the patients on whom there was a contra-indications to the use of anti-arrhythmic drugs, Propafenone was administered orally, on a long-term basis, at the usual dose of 600-900 mg per 24 hours. The efficacy and tolerance were evaluated according to the usual clinical and paraclinical criteria (EKG, Holter) on the 15th day, then every month during the treatment period. The efficacy of the treatment was evaluated as very good in 54 p. cent of the cases, good in 25 p. cent of the cases, average in 8 p. cent of the patients and non-existent or non significant for 13 p. cent of the patients. Electrocardiographic alterations under Propafenone are already described: CF, PR, QRS. A cardiac undesirable side effect occurred 102 times, most often a sinus bradycardia type (n = 26), atrio-ventricular conduction disorders (n = 22) or intraventricular conduction disorders (n = 26), disorders of cardiac decompensation (n = 10) or arrhythmogenic effect (n = 18). Other side effects are gastro-intestinal in nature (taste alterations, nausea, vomiting, gastralgia) for 23 p. cent of the patients treated, neuro-sensorial in origin (dizziness, visual disorders, tremors) for 13 p. cent of the patients or of another nature for 5 p. cent of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Efficacy and tolerance of propafenone in the treatment of cardiac rhythm disorders. Evaluation of a multicenter open trial on 3,687 patients]. 329 28

To exploit possible different non-cross-resistant mechanisms of cytotoxicity, 25 patients with advanced breast cancer were given combination chemotherapy consisting of iv mitoxantrone (7 mg/m2) and doxorubicin (30 mg/m2) every 3-4 weeks. The patients had predominantly visceral disease and received a median of six (range, one to 12) cycles of therapy. There were no complete responders, but 13 patients (52%) achieved partial remission lasting a median of 8 months (range, 4-21+). Three patients (12%) had disease stabilization and nine (36%) had disease progression. Hematologic toxicity was generally mild, with median wbc count and platelet count nadirs of 1900/mm3 (range, 700-3100) and 160,000/mm3 (range, 49,000-406,000), respectively. One patient may have died from treatment-related sepsis (pneumonia), but lymphangitic lung disease was not excluded. Hair loss progressing to severe alopecia over several treatment cycles was relatively common, affecting seven of 16 evaluable patients (44%). Vomiting was mild or absent in 17 (71%) of 24 evaluable patients. Three of 15 patients in whom serial measurements of left ventricular ejection fraction were performed developed significant reductions compatible with anthracycline-induced cardiotoxicity. Two of these patients also had pericardial effusions and one developed congestive heart failure. In conclusion, mitoxantrone and doxorubicin is an active, well-tolerated drug combination for the treatment of advanced breast cancer but may have appreciable cardiotoxicity.
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PMID:Phase II trial of a combination of doxorubicin and mitoxantrone in metastatic breast cancer. 330 79

We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 evaluable children 1-19 years old. Twenty-seven had leukemia and 15 had various solid tumors. The drug was administered in escalating doses of 10 to 40 mg/m2/course in 3 equal fractions over 3 consecutive days at 14- to 21-day intervals. Myelosuppression and mucositis were the limiting toxicities for short-term administration. Nausea, vomiting, and elevation of liver enzymes and bilirubin were the other toxicities encountered. Peak toxicity occurred 2 weeks after drug administration with median recovery by day 24. All but 4 patients with solid tumors had prior anthracyclines. Mild cardiac function changes without clinical symptoms were observed in 17 of 35 patients measured by serial cardiac evaluations. In addition, there were 4 patients with congestive heart failure. On postmortem examination, 4 patients had changes consistent with anthracycline cardiomyopathy at a prior median total anthracycline dose of 175 mg/m2. The maximum tolerated dose for patients with solid tumors was 15 mg/m2 course in 3 divided doses. Patients with leukemia tolerated 30 mg/m2/course. Six of 15 evaluable patients with acute lymphoblastic leukemia who received greater than or equal to 30 mg/m2 idarubicin achieved a remission (M1 marrow status). The plasma clearance of idarubicin fits a 3-compartment model with a harmonic mean half-life of 2.4 min, 0.6 h, and 11.3 h for alpha, beta, and gamma phases, respectively. Idarubicinol was the only metabolite detected in the plasma and it accumulated during the 3 days of therapy. Idarubicin is similar to daunorubicin in pharmacology and toxicity. While the cardiotoxic dose still must be delineated, the complete remission achieved in multiple relapsed patients with acute lymphoblastic leukemia indicate promising activity in at least that disease.
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PMID:Phase I and clinical pharmacological study of 4-demethoxydaunorubicin (idarubicin) in children with advanced cancer. 347 21

High-dose doxorubicin has shown considerable activity in both previously treated and previously untreated patients with lymphoma. Because of the toxicities of doxorubicin at high dose, we elected to study a new anthracycline at doses comparable to doxorubicin at high dose, to assess response and toxicity. Epirubicin was administered at doses of 120 mg/m2, 150 mg/m2, and 180 mg/m2 every 3 weeks (maximum four doses) to groups of six patients with previously treated intermediate- and high-grade lymphoma. Sixteen of the patients had received significant prior therapy with an anthracycline and/or anthracenedione. At all dose levels, myelosuppression was severe, with median granulocyte nadirs less than 504/mm3. Hematological recovery occurred by day 21 at the 120 mg/m2 and 150 mg/m2 dose levels, allowing for the next cycle of therapy. However, at the 180 mg/m2 dose level, the majority of patients failed to have hematological recovery by the day of the next scheduled therapy. Forty-two % of patients (eight patients) had fever/neutropenia, and required antibiotics. One treatment-related septic death occurred (at 150 mg/m2). Alopecia (68%), fever immediately following treatment (63%), mild/moderate stomatitis (58%), and nausea/vomiting (53%) were the most common nonhematological toxicities. These toxicities were independent of the dose levels and were not dose limiting. A significant change (greater than or equal to 0.10) in the radionuclide ejection (EF) was seen in seven patients. The median of the entire group of patients fell from 0.63 to 0.56. No patient developed clinical or radiological evidence of congestive heart failure. A response rate of 58% (two complete responses, nine partial responses) was achieved with a median duration of 5 months (range, 1-15+). High-dose epirubicin can be successfully utilized in patients with previously treated lymphoma. The only dose-limiting toxicity observed at these dose levels was the lack of hematological recovery by day 21 with 180 mg/m2. Since epirubicin at high dose will be incorporated into high-dose anthracycline regimens in previously untreated patients utilizing a 3-week treatment cycle, 150-180 mg/m2 may be the maximally tolerated dose for such studies.
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PMID:Phase I-II trial of high-dose epirubicin in patients with lymphoma. 347 45

Ninety patients with breast cancer refractory to cyclophosphamide/fluorouracil/methotrexate (CMF) have been randomized in their treatment, receiving either doxorubicin or mitoxantrone. Seventy-nine have received two full courses of therapy. Twelve of the 40 (30%) who initially received doxorubicin responded, whereas eight of the 47 (17%) who received mitoxantrone responded. These rates are not statistically different. The degree of myelosuppression was equivalent. Patients who received mitoxantrone had less nausea, vomiting, alopecia, and fatigue. Controllable clinical congestive heart failure developed in seven patients, and four others had a deterioration of noninvasive measures of cardiac function without clinical failure. One patient with clinical heart failure developing received only doxorubicin and one, only mitoxantrone, whereas the others received both agents. The duration of remission and time lapsed before disease progression were almost identical for the two regimens. This study included a crossover design. Two of 22 (10%) patients receiving doxorubicin and five of 24 (21%) receiving mitoxantrone as secondary therapy responded. This suggests that there is not absolute cross-resistance between these agents. We conclude that the efficacy of these two drugs is comparable in patients refractory to CMF, though the nonhematologic side effects of mitoxantrone are less.
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PMID:A comparison of mitoxantrone and doxorubicin in breast cancer. 351 41

Patients with metastasized breast cancer are incurable. Remissions with longer survival can be induced by chemotherapy in 50 to 80%, with 10 to 20% complete remissions, however, recurrence is unavoidable. Therefore the strategy of therapy in breast cancer must include two aspects: first prolongation of overall survival by multiple remissions with regimes that are not cross-resistant and secondly conservation of quality of life by minimization of therapy conditioned side-effects. Epirubicin, the new anthracycline derivate and analogue of doxorubicin (probably the most active chemotherapeutic agent against breast cancer) exhibits the same high activity but lower side-effects compared with the parent compound. Complete and partial remissions in 33% of 313 breast cancer patients could be achieved with epirubicin. In three other studies the efficacy and side-effects of epirubicin were compared with the established drug doxorubicin. The remission rate was nearly the same but the side-effects such as nausea, vomiting, stomatitis, bone marrow toxicity and congestive heart failure were lower. Five different studies with epirubicin in combination with other cytostatics have shown comparable results as adriamycin combinations. In a randomized multicenter study, 520 patients were treated with epirubicin or doxorubicin in combination with cyclophosphamide and fluorouracil. The remission rates were 52 vs. 54%, respectively, but the toxicity of the epirubicin combination group was significantly lower.
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PMID:[Epirubicin--results in breast cancer]. 352 68

239 patients were evaluable: 116 in the FAC arm, 123 in the FEC arm. There is no significant difference in the therapeutic responses between 2 regimens: 52 +/- 9% vs 49 +/- 9%. Duration of responses (273 vs 303 d) and overall survival were also similar. FEC appears less myelotoxic, less toxic also in terms nausea, vomiting and grade 3 alopecia than the adriamycin combination. 9 patients required treatment cessation due to grade 2 cardiac dysfunction with 3 CHF, against no case in the epirubicin regimen.
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PMID:[French FAC vs FEC study in advanced breast cancer]. 352 69

Seven hundred and ninety-six consecutive patients with operable primary breast cancer treated with doxorubicin-containing postoperative adjuvant chemotherapy between 1974 and 1982 were evaluated for assessment of the acute and long-term toxicities of the program. Most patients experienced nausea, vomiting, and alopecia, side effects that were totally reversible. Doxorubicin skin infiltration was observed in 6% of the patients. Hematologic toxicity was moderate, and only 26% of the patients had a granulocyte nadir of less than 1000 cells/ml. Febrile or infectious complications occurred in 6% of patients, of which 3% required hospitalization for observation and antibiotic treatment. No long-term hematologic changes were observed. Amenorrhea was reported by 80% of premenopausal patients. However, none of the patients under 30 years of age had menstrual abnormalities, whereas 96% of those 40-49 years of age developed amenorrhea. Amenorrhea was permanent for most women over 40, but for 50% of patients under 40 years of age, it was reversible. Endocrinologic studies showed that amenorrhea was a result of primary ovarian failure. The incidence of second malignant neoplasms was lower (1.3%) in the group treated with 5-fluorouracil, doxorubicin, and cyclophosphamide than in the historical control group (4.8%). Cardiac toxicity data was evaluated in 460 patients. When up to a cumulative dose of 300 mg/m2 was given, 1% of the patients developed congestive heart failure. In 4 of these 5, adequate control was achieved with medical treatment; 1 patient died as a consequence of cardiac toxicity.
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PMID:Immediate and long-term toxicity of adjuvant chemotherapy regimens containing doxorubicin in trials at M.D. Anderson Hospital and Tumor Institute. 353 81


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