Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty patients with locally advanced or metastatic breast cancer were treated with four cycles of ifosfamide/mesna 5 g m-2 and epirubicin 60 mg m-2 every 14 days with granulocyte colony-stimulating factor (G-CSF, Filgrastim). Complete remission occurred in six out of the 20 patients (30%, 95% confidence interval 12-54%) and there were 12 partial responders (60%, 95% confidence interval 37-81%), thus giving an overall response rate of 90% (95% confidence interval 63-97%). Two patients had progressive disease. The median duration of response for those patients with metastatic disease was 7.3 (1.3-20.1+) months. The median survival time for these patients was 15 (5.3-27.9+) months. Of the four patients treated with locally advanced disease three achieved a complete clinical response and one a partial response. Three out of four of these patients subsequently underwent a mastectomy, and in one of these no viable tumour was seen. Our conclusion is that this regimen is excellent palliation for metastatic disease and possibly useful neoadjuvant treatment.
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PMID:The use of granulocyte colony-stimulating factor to deliver four cycles of ifosfamide and epirubicin every 14 days in women with advanced or metastatic breast cancer. 753 18

We report about a patient with metastatic breast cancer treated with chemotherapy regime (CMF), who developed a febril leukopenia as well as a hyperuricemia. A single subcutaneous application of 300 micrograms Filgrastim led to a severe overstimulation with leukocytosis of max. 50,000 for about 8 days and hyperuricemia.
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PMID:[Persistent granulocytosis and hyperuricemia after a single G-CSF injection (Filgrastim) in treatment of chemotherapy-induced myelosuppression in metastatic breast carcinoma]. 754 54

Taxol was evaluated in metastatic breast cancer in three trials. In the first, a phase II study, 25 patients who had received only one prior regimen of chemotherapy received Taxol (starting dose of 250 mg/m2). The response rates were 12% complete, 44% partial, and 32% minor. The median duration of response was 9 months (range, 3 to 19 months). The median survival was 20 months (range, 5 to 29+ months). Toxic effects were granulocytopenia less than 500/mm3 in 85% of all courses but serious infection in only 6% of courses, myalgias, and cumulative neuropathy. The second trial was a phase I study of Taxol by 24-hour infusion sequenced with doxorubicin by 48-hour infusion as initial chemotherapy for metastatic disease. In arm 1, Taxol preceded doxorubicin. The starting doses were 125 mg/m2 Taxol, 60 mg/m2 doxorubicin. Neupogen (5 micrograms/kg) was given subcutaneously on days 5 through 19. Ten patients received 96 courses. The maximum tolerated dose was defined by mucositis and infection at the starting dose. Cumulative thrombocytopenia occurred in subsequent courses. The unexpectedly severe toxic effects at doses that were low by comparison to other studies suggested schedule-related toxicity. Therefore, in arm 2 the sequence has been reversed: doxorubicin precedes Taxol. Doses have been escalated to 180 mg/m2 Taxol with 60 mg/m2 doxorubicin without dose-limiting toxic effects occurring. The third trial, a phase II study in patients who have received three or more prior chemotherapy regimens, is ongoing. Twenty-one of a planned 35 patients have been entered. Taxol has shown significant antitumor activity in minimally pretreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The M. D. Anderson Cancer Center experience with Taxol in metastatic breast cancer. 791 22

The impact of filgrastim on the use of health care resources during recovery from autologous bone marrow transplantation (ABMT) was studied. The charts for patients with metastatic breast cancer treated with ABMT at a general hospital between November 1989 and July 1993 were reviewed by Blue Cross of Western Pennsylvania. The 58 patients were divided into five groups: group 1-bone marrow purged, no filgrastim therapy; group 2-bone marrow not purged, no filgrastim therapy; group 3-bone marrow purged, filgrastim therapy after ABMT; group 4-bone marrow not purged, filgrastim therapy after ABMT; and group 5-peripheral blood stem cells (PBSCs) given, followed by filgrastim therapy. The groups were compared for total length of stay (LOS), number of days the absolute neutrophil count (ANC) was < 500/cu mm, total number of days of filgrastim therapy, and total number of cumulative unit days of antimicrobial use. Total LOS was shorter for patients who received filgrastim (groups 3-5) than for patients who did not. Filgrastim was associated with fewer days of ANC < 500/cu mm in groups 4 and 5. The total number of cumulative unit days of antimicrobial use was lower in filgrastim recipients. Patients who received PBSCs needed fewer days of filgrastim therapy than the other filgrastim recipients. The health insurance company determined that, as a result of filgrastim therapy and PBSC transplantation, ABMT costs to the company have dropped by more than 50% since 1990. Patients now have available an alternative to conventional therapy for metastatic breast cancer without prejudice or penalty from their payer.
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PMID:Cost-effectiveness of autologous bone marrow transplantation. 884 40

Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2; III, 24 mg/m2; IV, 32 mg/m2; and LV, 300 mg, followed by FU, 350 mg/m2, on days 1-3. Filgrastim was given at 5 micrograms/kg/day subcutaneously on days 4-13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as the dose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts: IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts < or = 20,000/microL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%) achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.
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PMID:Mitoxantrone dose augmentation utilizing filgrastim support in combination with fixed-dose 5-fluorouracil and leucovorin in women with metastatic breast cancer. 915 Aug 98

This phase I dose-finding study examined the effects of the combination of doxorubicin and docetaxel (Taxotere) in 42 women with metastatic breast cancer. The combination was studied at six different dosing levels. The maximum tolerated doses were defined as doxorubicin, 50 mg/m2, and docetaxel, 85 mg/m2, with sepsis as the dose-limiting toxicity. Activity was observed at all dose levels, especially at the highest dose levels (50/60, 50/75, 50/85, and 60/60 mg/m2), with a response rate of 81% (95%; confidence interval, 62.5% to 92.5%) in patients treated at these dose levels. The response rate in patients with visceral disease was 74%, and 82% in patients with liver metastasis. Adjuvant chemotherapy with or without anthracyclines did not affect the response rate. The recommended doses were doxorubicin, 50 mg/m2, and docetaxel, 75 mg/m2, or 60 mg/m2 of both drugs, administered on day 1 every 3 weeks, without granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]) support. Neutropenia was the only grade 3 or 4 adverse event. There were no cases of congestive heart failure, a significant decrease in left-ventricular ejection fraction, or interruption of treatment because of fluid retention.
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PMID:Docetaxel in combination with doxorubicin: a phase I dose-finding study. 921 22

A pilot phase II study examined the feasibility of 75 mg/m2 of docetaxel (Taxotere) in combination with 50 mg/m2 of doxorubicin and 500 mg/m2 of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation. Patients were divided into three groups: one group received 8 courses of docetaxel/doxorubicin/cyclophosphamide; the second received 4 to 6 courses of the same combination with cell sampling, followed by high-dose chemotherapy with autologous peripheral blood stem-cell transplantation; and the third group's regimen was identical to that of the second, with additional granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]). Of 28 patients (149 courses) evaluable for toxicity and response, the overall response rate was 82%, with 5 (18%) complete responses and 18 (64%) partial responses. The most frequent hematologic toxicity was neutropenia; grade 4 neutropenia occurred in 86% of patients, with febrile neutropenia in 9 patients (18%). There was no incidence of infection, possibly because of the administration of oral ciprofloxacin (Cipro) from days 5 to 15 of each cycle. Nonhematologic adverse events were not severe; there was no significant cardiotoxicity. Future randomized trials of docetaxel/doxorubicin/cyclophosphamide as first-line adjuvant therapy of high-risk patients and as induction chemotherapy are in development.
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PMID:Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. 921 24

Preclinical studies show that docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) are synergistic against MA 13/C mammary adenocarcinoma. Both agents are highly active as monotherapy in a number of tumors, including metastatic breast cancer. Therefore, we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors. A total of 45 patients were enrolled and received cyclophosphamide followed by docetaxel, both administered as 1-hour intravenous infusions once every 3 weeks. The dose levels of cyclophosphamide/docetaxel were 600/60 mg/m2 (group 0), 600/75 mg/m2 (group I), 700/75 mg/m2 (group 2), 800/75 mg/m2 (group 3), 800/85 mg/m2 (group 4), 800/75 mg/m2 (group 5), and 800/85 mg/m2 (group 6). Patients with dose-limiting neutropenia in groups 5 and 6 received 300 micrograms of granulocyte colony-stimulating factor (G-CSF) (filgrastim [Neupogen]) support on days 2 through 9 during subsequent cycles of chemotherapy. All patients received premedication with 8 mg of dexamethasone twice daily for 5 days, beginning 1 day prior to chemotherapy. The dose-limiting toxicity was neutropenia fever. The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m2 in previously treated patients and 800/75 mg/m2 in previously untreated patients. G-CSF support did not allow for further dose escalation. Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69% in 32 patients with metastatic breast cancer (including 3 patients who achieved complete responses).
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PMID:Combination docetaxel/cyclophosphamide in patients with advanced solid tumors. 936 40

Paclitaxel is active in metastatic breast cancer. Combination studies have demonstrated complex interactions between paclitaxel and other cytotoxic agents, including sequence-dependent cytotoxic, toxicological, and pharmacological effects. The principal objectives of this study were to determine the maximum tolerated doses of paclitaxel (3-h infusion) and cyclophosphamide (1-h infusion) administered every 3 weeks with granulocyte colony-stimulating factor (Filgrastim) and to determine if the sequence-dependent toxicological effects that have previously been observed with this combination when paclitaxel was administered over 24 h were evident when paclitaxel was administered over 3 h. Fifteen women with metastatic breast cancer were treated. Starting doses were 200 mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, with granulocyte colony-stimulating factor (5 micrograms/kg/day) given s.c. beginning 24 h after chemotherapy. Doses of both drugs were escalated in cohorts of at least four patients. The sequence of drug administration was alternated with each consecutive patient and with each subsequent course of therapy in each individual patient, enabling the evaluation of sequence-dependent toxicological and pharmacological effects. Severe myelosuppression was the principal dose-limiting toxicity for this regimen, precluding dose escalation above 200 mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, the maximum tolerated dose for this combination on this schedule. As has been previously demonstrated with this combination, when paclitaxel is administered over 24 h, the hematopoietic toxicity was sequence dependent. Paired analysis of toxicity data using each patient as her own control indicated more severe hematological toxicity in courses in which paclitaxel was administered first. There was no evidence of sequence-dependent effects on the pharmacokinetics of these drugs that might account for this phenomenon. The impact of drug sequencing on toxicity should be considered in the further development of combination therapy containing alkylating agents and paclitaxel, when the latter is administered over 3 h.
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PMID:Sequence-dependent hematological toxicity associated with the 3-hour paclitaxel/cyclophosphamide doublet. 951 22

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


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