Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attempting to develop a new active, convenient regimen, we initiated a phase I study of paclitaxel (Taxol; Bristol-Myers squibb Company, Princeton, NJ) combined with epirubicin (Farmitalia Carlo Erba, Milan, Italy) in patients with metastatic breast cancer. In addition to standard eligibility criteria, patients with chemotherapy-naive metastasis and at least one measurable lesion had to have left ventricular ejection fractions of at least 50%; the metastatic relapse had to have occurred more than 6 months after adjuvant treatment. Anthracycline-pretreated patients could not have received cumulative doses of more than 300 mg/m2 doxorubicin, 450 mg/m2 epirubicin, or 70 mg/m2 mitoxantrone. An intravenous bolus dose of epirubicin was followed by a 3-hour paclitaxel infusion, with courses repeated every 3 weeks. To date, seven dose levels have been investigated and 31 patients have been treated, 19 of whom had already received anthracyclines. Grades 3 and 4 neutropenia occurred in 37% and 19% of 123 courses, respectively, with five episodes of febrile neutropenia. Grade 2 or 3 neurotoxicity has been observed in 42% of patients and cardiac toxicity in four patients (13%), all of whom had already received anthracyclines. One patient experienced transient myocardial ischemia, one had an asymptomatic decrease in ejection fraction, and two patients had clinical heart failure that required treatment. Dose-limiting toxicity was reached at dose level 5 (paclitaxel 200 mg/m2 plus epirubicin 60 mg/m2), with two of three patients experiencing febrile neutropenia. Reducing the epirubicin dose to 50 mg/m2, however, allowed the paclitaxel dose to be escalated to 250 mg/m2. At this dose level, only one of six patients experienced febrile neutropenia. At a preliminary response evaluation (dose levels 1 to 6), 11 patients (44%) had partial responses, 12 patients (48%) had stable disease, and disease progressed in two patients. We conclude that the combination paclitaxel/epirubicin is safe for patients with metastatic breast cancer and, at this early evaluation, shows promising antitumor activity. Additional patients will be treated at dose level 5 to confirm whether dose-limiting toxicity occurs at this step. Indeed, we took into consideration that dose-limiting toxicity observed at this particular dose level in two of three patients might be due to hazard, since paclitaxel dose escalation up to 250 mg/m2 was further possible in association with 50 mg/m2 epirubicin.
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PMID:Phase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety. 862 32

In an attempt to develop new, active, and convenient outpatient combination-chemotherapy regimens for patients with metastatic breast cancer, we performed two phase I studies combining paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus anthracycline for the first-line treatment of metastatic disease, without the use of hematopoietic growth factors. Study I was designed to test the tolerability and antitumor activity of a 3-hour infusion of paclitaxel in combination with an epirubicin intravenous bolus. Study 2 explored a three-drug chemotherapy regimen: a 3-hour paclitaxel infusion with epirubicin and cyclophosphamide. Courses were repeated every 3 weeks. If any dose-limiting events occurred in two or more of six patients in the first course of a given dose level, that dose level was defined as the maximum tolerated dose. Dose-limiting criteria included the following: neutrophils less than 0.25 x 10(9)/L lasting for > or = 5 days, any febrile neutropenia, World Health Organization grade 4 thrombocytopenia, World Health Organization grade > or = 3 nonhematologic toxicity or grade > or = 3 mucositis for more than 5 days, and absence of hematologic recovery at day 35. In both studies, paclitaxel doses were escalated in subsequent groups of three to six patients. For study I, the initial dose level consisted of paclitaxel (110 mg/m2)/epirubicin (50 mg/m2). To date 40 patients have entered the study at eight dose levels. Of the 181 cycles evaluated, grade 3 or 4 neutropenic episodes were observed in 63% of courses, with only five episodes of febrile neutropenia. Grade 2 or 3 neurotoxicity was observed in 43% of patients. Two patients experienced clinical heart failure. The dose-limiting toxicity has not been reached so far. At dose level 7 (paclitaxel [250 mg/m2]/epirubicin [50 mg/m2]), only one patient of six experienced febrile neutropenia. We are currently testing paclitaxel (200 mg/m2)/epirubicin (75 mg/m2). Preliminary evaluation of response documents two complete and 16 partial responses in 37 evaluable patients (48% overall response rate). In study 2, the initial dose level consisted of paclitaxel (150 mg/m2)/epirubicin (50 mg/m2)/cyclophosphamide (500 mg/m2). To date, three dose levels have been investigated in 16 evaluable patients (82 cycles). Grade 3 or 4 neutropenic episodes were observed in 80% of courses, and five episodes were associated with neutropenic fever. Grade 2 neurotoxicity was observed in 28% of patients. The dose-limiting toxicity has not been reached, and we are currently investigating dose level 4 (paclitaxel 225 mg/m2). These trials confirm the tolerability of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide. The antitumor activity is encouraging.
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PMID:Phase I studies of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide in patients with metastatic offast cancer: the French experience. 907 33

A multicenter nonrandomized study was designed to assess the efficacy (response rate and duration of relapse-free survival) and safety of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 200 mg/m2 given as a 3-hour intravenous infusion with premedication every 3 weeks, followed by mitoxantrone 12 mg/m2, given as an intravenous push every 3 weeks, in patients with metastatic breast carcinoma. So far, 30 patients have entered the study and 27 are evaluable for response. All patients had advanced metastatic breast cancer and have been extensively pretreated with chemotherapy (28 patients), radiotherapy (13 patients), and hormonotherapy (24 patients). Fourteen patients (46.7%) have been previously treated with anthracyclines, and disease progressed in seven (23.3%) during anthracycline treatment. One patient had a complete remission and 14 a partial remission for a total remission rate of 55.6%. One of the 15 patients entering remission developed heart failure and was withdrawn from the protocol after 4 months in remission. She then relapsed and died 9 months after entering protocol. The remaining 14 patients continue to respond and their remission durations range from 4+ to 12+ months (mean, 9 months; 95% confidence interval [CI] 7.96 to 10.04). Eleven patients (40.7%) developed minor responses or disease stabilization lasting from 1.5 to 11.4+ (mean, 3.5 months; 95% CI, 1.9 to 6.0) and one of them had disease progression after 3.5 months and is still alive whereas another one who had disease progression died at 1.5 months. Four patients failed to respond and their disease progressed during protocol treatment; two of them died at 6.7 months while the other two are alive at 3.4 and 9.8 months. Overall survival ranged from 1.5 to 13+ months (mean, 6.7 months; 95% CI, 5.5 to 7.9). In the group of 14 anthracycline-pretreated patients, seven showed a partial remission, six a minor response or disease stabilization, and one had disease progression. Response duration ranged from 1.5 to 12+ months (mean, 6.1 months; 95% CI, 4.2 to 8.0); the three patients whose disease progressed died at 1.5, 6.7, and 8.8 months. Bone marrow toxicity was dose-limiting and caused treatment delays as well as dose de-escalation of both drugs in eight patients.
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PMID:Treatment of advanced and relapsing breast cancer with a combination of paclitaxel and mitoxantrone. South-Central Hellenic Oncology Group. 907 35

This ongoing phase II trial was designed to determine the antitumor activity and cardiotoxicity of a combination of doxorubicin (50 mg/m2) and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 to 225 mg/m2 over 3 hours) as first-line chemotherapy for metastatic breast cancer. Of 76 patients entered so far, 57 who had received at least three courses of chemotherapy are assessable for efficacy and cardiac toxicity. A slight majority (57%) of the patients entered had prior adjuvant chemotherapy, including 33% with anthracycline-containing combinations. An objective response was achieved by 70% of patients, with 18% complete responders. The main noncardiac toxicities were alopecia, neutropenia, mucositis, and peripheral neuropathy. Overall, after a median cumulative doxorubicin dose of 350 mg/m2, the evolution of left ventricular ejection fraction (LVEF) values did not significantly decrease from baseline to the sixth course of therapy. However, LVEF values decreased significantly in eight patients (14%). The LVEF decreased by more than 14% over basal values in three patients, although the final determination was still above the lower limits of normal. The remaining five patients had LVEF decreases that fell below the lower limits of normal (33% to 48%). None of the patients developed clinically evident heart failure. Our results indicate that the combination of doxorubicin (50 mg/m2) plus paclitaxel (175 to 225 mg/m2) is effective and does not induce a clinically relevant cardiotoxicity.
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PMID:Paclitaxel plus doxorubicin in metastatic breast cancer: preliminary analysis of cardiotoxicity. 937 88

The case concerns a 56 year old male with the diagnosis of squamous cell carcinoma, which clinically presented as a rapidly increasing cardiac tamponade. The patient underwent a pericardio-centesis. Due to the expansion of the process within the bronchus, the patient underwent chemotherapy according to the Taxol + Carboplatine scheme. After 8 months of treatment the patient was hospitalized again due to a further increase in fluid in the pericardium, and symptoms of cardiac insufficiency which lead to patient death. Autopsy revealed neoplastic change within the pericardium (fibrinous-hemorrhagic pericarditis and hemopericardium). Cardiac tumors occur rarely, they may be primary or secondary. Squamous cell carcinoma metastases may be the cause of pericardial effusion, which is associated with poor prognosis.
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PMID:[Cardiac tamponade as the first clinical manifestation of squamous cell carcinoma]. 1215 50