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Biomedical subjects

Edgardo Rivera

Publications and source records attributed to Edgardo Rivera.

36 records · Page 2Linked to original sources
PubMed2003

Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer.

PURPOSE: We conducted a phase II clinical trial to determine the clinical efficacy and safety of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients were eligible if they had measurable disease, no prior chemotherapy for metastatic disease, and a performance status </= 2 on the Zubrod scale. Patients received pegylated liposomal doxorubicin 24 mg/m2 intravenously on day 1, plus gemcitabine 800 mg/m2 intravenously on days 1 and 8 of each 21-day cycle. RESULTS: Of 49 patients enrolled, 27 had received prior adjuvant chemotherapy (19 with an anthracycline). Prior median cumulative anthracycline dose was 240 mg/m2. In total, three complete responses and 21 partial responses were achieved in 46 assessable patients, for an overall response rate of 52% (95% confidence interval, 37% to 67%). Responses were observed in 11 (58%) of 19 patients with previous anthracycline exposure. Median response duration was 5.6 months, time to progression was 4.5 months, and overall survival was 16.1 months. Although the most common grade 3 to 4 toxicities were hematologic, few neutropenic complications resulted. The most frequent nonhematologic toxicities were nausea and vomiting, fatigue, stomatitis, and hand-foot syndrome. One patient previously treated with an anthracycline developed a transient decrease (21%) in the left ventricular ejection fraction, with cardiac function recovering within 2 months. CONCLUSION: Pegylated liposomal doxorubicin in combination with gemcitabine is active and well tolerated in patients with metastatic breast cancer. Median overall survival was 16.1 months, and approximately 78% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving front-line therapy for their metastatic breast cancer.

Adult↗
PubMed2003

Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy.

BACKGROUND: The current study was conducted to report the severity and management of canalicular and nasolacrimal duct stenosis as a side effect of docetaxel therapy and to report the outcomes of surgical intervention for this condition. METHODS: The records of 148 patients with epiphora associated with docetaxel therapy who were evaluated at the Ophthalmology Service at The University of Texas M. D. Anderson Cancer Center were reviewed. The frequency of docetaxel administration, the dose intensity, the cumulative dose of docetaxel, and any concomitant chemotherapeutic agents were recorded. Each patient underwent an ophthalmologic examination and in-office probing and irrigation. The patients either were treated with topical steroids or offered a surgical procedure for canalicular stenosis- (silicone intubation, dacryocystorhinostomy [DCR] with the placement of silicone tubes, or DCR with the placement of Pyrex glass tubes), depending on the severity of the canalicular stenosis. RESULTS: Docetaxel was given weekly in 71 patients, every 2 weeks in 5 patients, and every 3 weeks in 72 patients. Thirty patients (59 eyes) who received weekly docetaxel underwent surgery to correct epiphora. Twenty-three patients (39 eyes) were treated with temporary silicone tube placement, 9 patients (13 eyes) were treated with DCR with temporary silicone tube placement, and 4 patients (7 eyes) were treated with DCR with permanent Pyrex glass tube placement. Twenty-nine of the 30 patients who underwent surgery reported improvement or total resolution of epiphora after the procedure. Ten additional patients (20 eyes) who received weekly docetaxel had complete closure of their canaliculi but elected not to undergo surgery. Of special note were two patients who received weekly docetaxel in the neoadjuvant setting and developed complete closure of the canaliculi. Of the patients who received docetaxel every 2 or 3 weeks, only 3 required a surgical intervention to correct epiphora; none required Pyrex glass tube placement. CONCLUSIONS: Canalicular and nasolacrimal duct obstruction is a common side effect of weekly docetaxel therapy and can occur even when this drug is used in the neoadjuvant setting. The results of the current study indicate that early temporary silicone intubation in symptomatic patients receiving weekly docetaxel can prevent further closure of the lacrimal drainage apparatus and obviate more involved surgical interventions and permanent Pyrex glass tube placement. Cancer 2003;98:504-7.

Adult↗
PubMed2003

Targeted filgrastim support in patients with early-stage breast carcinoma: toward the implementation of a risk model.

BACKGROUND: Severe neutropenia, a common consequence of chemotherapy, may result in infectious complications and hospitalizations. Preventive treatment with colony-stimulating factors is limited because of the inability to predict which patients will develop neutropenic complications. To the authors' knowledge, the current study is the first large prospective validation of a risk model in patients with early-stage breast carcinoma. METHODS: Patients with Stage I-III breast carcinoma who were receiving adjuvant chemotherapy (n=624) were assigned to risk groups based on first-cycle absolute neutrophil count (ANC) nadirs of <0.5 x 10(9)/L. Filgrastim (a recombinant human granulocyte-colony-stimulating factor) was administered from Cycle 2 onward to high-risk patients. Dose intensity and rates of neutropenic complications, including febrile neutropenia and hospitalization resulting from it, were calculated for each group and compared. High-risk patients were matched by chemotherapy regimen, stage of disease, age, and baseline ANC to historic-control patients and outcomes were compared within the matched pairs. RESULTS: Both risk groups were found to have a similar proportion of patients receiving >85% of the dose intensity (95.8% vs. 94.4%). The rate of febrile neutropenia and hospitalization in the low-risk group (n=264) was 2.6% (95% confidence interval [95% CI], 0.7-4.5%) and 0.8 (95% CI, -0.3-1.9%), respectively. The high-risk group was 2.6 times more likely to receive a full dose of chemotherapy, but no higher risk of neutropenic complications was reported compared with the matched controls. CONCLUSIONS: The risk-related prophylactic administration of filgrastim facilitated the delivery of planned chemotherapy to the high-risk group of patients. However, further research is needed to confirm the results obtained in the current study in a randomized trial, if feasible, and in other chemotherapy and disease settings.

Adult↗
PubMed2003

First-cycle absolute neutrophil count can be used to improve chemotherapy-dose delivery and reduce the risk of febrile neutropenia in patients receiving adjuvant therapy: a validation study.

BACKGROUND: The nadir value of the absolute neutrophil count (ANC) in the first cycle of chemotherapy is an effective predictor of subsequent neutropenic events. This study was designed to validate an earlier published study based on a retrospective data analysis from a prospective randomized clinical trial. METHODS: The original published model was applied to a trial of 143 patients to cross-validate the model. We also tested the specification of the model on our data by using a logistic regression model with several variables, including first-cycle nadir ANC, age, menopausal status, hormone-receptor status, previous radiotherapy, and first-cycle decrease in hemoglobin concentration. Patients received fluorouracil, doxorubicin, and cyclophosphamide every 21 or 28 days for six cycles without hematopoietic support from colony-stimulating factor. RESULTS: In the cross-validation analysis, the original model successfully classified patients by risk of neutropenic events (C = 0.78). When the model specification was tested, first-cycle nadir ANC was the sole significant (P < 0.0001) predictor of neutropenic events and the model had a good predictive power (C = 0.78). The estimated relative risk of 4.8 did not differ from the risk cited in the original model (P = 0.91). A significantly higher percentage of our patients with a low first-cycle nadir ANC of 0.25 x 10(9)/liter or less experienced febrile neutropenia (30% versus 10%, P = 0.04) and received at least 85% of the planned dose intensity (55% versus 32%, P = 0.05). CONCLUSIONS: The original risk model used to predict neutropenic events was validated by our study. This information can be used to target high-risk patients for prophylactic treatment with filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) in chemotherapy cycles 2 to 6.

Antineoplastic Agents↗
PubMed2003

Cost of chemotherapy-induced thrombocytopenia among patients with lymphoma or solid tumors.

BACKGROUND: The purpose of this study was to estimate the mean incremental cost of chemotherapy-induced thrombocytopenia and the drivers of cost. Another goal was to estimate the impact of depth and duration of thrombocytopenia on the cost of thrombocytopenia. METHODS: A retrospective cohort, consisting of a random sample of 75 solid tumor or lymphoma patients who developed chemotherapy-induced thrombocytopenia (</= 50,000 platelets per microl), was chosen. The number of each type of resource used during 217 cycles with and 300 cycles without thrombocytopenia were multiplied by the cost of each resource and summed to yield the total cost of care (in 1999 dollars from the provider's perspective). RESULTS: Compared with cycles without thrombocytopenia, the mean incremental cost of thrombocytopenia was $1037 per cycle. However, 60% of cycles were usual cost, with a mean cost of thrombocytopenia of $43 per cycle less than control cycles. Twelve percent of cycles were high cost (mean incremental cost = $612 per cycle); 28% were very high cost (mean incremental cost = $3519). The excess cost during high-cost cycles was due to high consumption of prophylactic platelet transfusions and during very high-cost cycles to both higher platelet transfusion consumption and to a high incidence of major bleeding episodes. CONCLUSIONS: Although thrombocytopenia is a common complication of chemotherapy, only 40% of cycles with thrombocytopenia would be considered high or very high cost. Interventions targeted at this subset of cycles could significantly reduce the cost of thrombocytopenia provided they are initiated early enough in the chemotherapy experience to be effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Liposomal anthracyclines in metastatic breast cancer: clinical update.

Anthracyclines are a mainstay of therapy for patients with metastatic breast cancer. However, their use has been limited by associated toxicities, including myelosuppression, alopecia, nausea and vomiting, stomatitis, and most importantly, cardiotoxicity. Liposomal anthracyclines were developed to increase the therapeutic index of conventional anthracyclines by maintaining antitumor efficacy while improving the safety profile. There are currently three liposomal formulations: liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin. Only one phase I study has been conducted with liposomal daunorubicin for metastatic breast cancer. Liposomal doxorubicin has shown comparable efficacy with conventional doxorubicin and less toxicity. Pegylated liposomal doxorubicin is the most widely studied of the liposomal anthracyclines and has demonstrated similar efficacy to conventional doxorubicin and a better safety profile, including significantly less cardiotoxicity, in patients with metastatic breast cancer. Pegylated liposomal doxorubicin has shown efficacy as a single agent and in combination with many agents, including cyclophosphamide, paclitaxel, docetaxel, and gemcitabine, with response rates ranging from 33%-75%. Growing evidence supports the use of pegylated liposomal doxorubicin as first-line treatment for patients with metastatic breast cancer, owing to its antitumor activity in both anthracycline-naïve patients and in patients with previous anthracycline exposure.

Anthracyclines↗
PubMed2003

Current status of liposomal anthracycline therapy in metastatic breast cancer.

Doxorubicin is a mainstay for the treatment of metastatic breast cancer (MBC); however, its use is limited by toxicity, particularly cardiotoxicity. Novel drug delivery systems using liposomes have been developed to maintain the clinical utility of conventional doxorubicin while minimizing cardiotoxicity. Three liposomal anthracyclines have been developed: liposomal daunorubicin, nonpegylated liposomal doxorubicin, and pegylated liposomal doxorubicin. Liposomal daunorubicin, currently approved in the United States for the treatment of AIDS-related Kaposi sarcoma, has shown preliminary activity in MBC in a phase I trial; further investigation is ongoing. Nonpegylated liposomal doxorubicin, which is not available in the United States, has demonstrated activity similar to that of conventional doxorubicin (both as a single agent and in combinations). Pegylated liposomal doxorubicin has demonstrated activity in phase II and III trials when used alone or in combination with other chemotherapeutic agents in patients with MBC. It is currently approved in the United States and Europe for AIDS-related Kaposi sarcoma and platinum/paclitaxel-refractory ovarian carcinoma; in Europe and Canada, it is also approved as monotherapy for MBC. In addition, accumulating evidence suggests that the combination of liposomal anthracyclines (pegylated and nonpegylated) and trastuzumab is active, with acceptable toxicity. Based on these encouraging experiences, randomized clinical trials are ongoing or planned to further assess the therapeutic potential of pegylated liposomal doxorubicin as a single agent and in combination with other chemotherapeutic agents and targeted agents, such as trastuzumab, for MBC.

Antibiotics, Antineoplastic↗
PubMed2002

Phase II study of liposomal annamycin in the treatment of doxorubicin-resistant breast cancer.

Liposomal annamycin (L-AN) has shown antitumor activity in preclinical studies. It may selectively target tumors and bypass MDR-1 resistance. A total of 13 women with doxorubicin-resistant breast cancer were treated on this phase II study. The median number of prior chemotherapy regimens was two, and six patients had two or more organ sites of involvement. L-AN was administered at 190-250 mg/m(2) as an i.v. infusion over 1-2 h every 3 weeks. No responses were observed. Of the 13 patients, 12 had clear deterioration and new tumor growth after one or two courses. The 13th patient had prolonged grade 2 thrombocytopenia after one course, and was taken off study when the lung metastases increased 62 days after treatment. L-AN at this dose and on this schedule had no detectable antitumor activity in patients with doxorubicin-resistant metastatic breast cancer.

Adult↗
PubMed2002

Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma.

PURPOSE: The authors conducted a single-institution Phase I clinical trial to determine the maximum tolerated doses and to define the toxic effects of oral eniluracil and oral 5-fluorouracil (5-FU) combined with docetaxel in patients with metastatic breast carcinoma. PATIENTS AND METHODS: Patients with metastatic breast carcinoma were eligible if they had disease progression after anthracycline-based therapy and had never been exposed to taxanes. The starting doses of oral eniluracil and oral 5-FU were 11.5 mg/m(2) and 1.15 mg/m(2), respectively, twice daily on Days 1-14. Docetaxel was given intravenously at a starting dose of 50 mg/m(2) on Day 1 only. The dose of docetaxel was escalated among cohorts until a maximum tolerated dose was reached. Courses were repeated every 21 days. RESULTS: The authors treated 19 patients with Stage IV breast carcinoma, of whom 5 had received prior chemotherapy for their metastatic disease. Fifty-three percent had a performance status of 1, and 53% had bone or soft tissue involvement as the dominant site of disease. All patients had received prior therapy with doxorubicin. The dose-limiting toxicity was neutropenic fever. No episodes of sepsis were observed. Significant antitumor activity was observed with a total of two complete and nine partial responses. The recommended doses for Phase II studies are 72 mg/m(2) docetaxel on Day 1 and 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice daily for a total of 14 days, with courses being repeated every 21 days. CONCLUSIONS: The combination of oral eniluracil/5-FU and intravenous docetaxel is a safe and well tolerated regimen. Significant antitumor activity is associated with this combination.

Administration, Oral↗
PubMed2002

Multicenter phase II study of a 28-day regimen of orally administered eniluracil and fluorouracil in the treatment of patients with anthracycline- and taxane-resistant advanced breast cancer.

PURPOSE: Eniluracil (776C85), a potent inactivator of dihydropyrimidine dehydrogenase, allows fluorouracil (5-FU) to be administered orally on a schedule that simulates continuous-infusion 5-FU. The primary objective of this study was to estimate the objective tumor response rate of orally administered eniluracil and 5-FU in the treatment of anthracycline- and taxane-resistant advanced breast cancer. PATIENTS AND METHODS: Patients with anthracycline- and taxane-resistant advanced breast cancer were enrolled onto this open-label, phase II, multicenter study. Patients received orally administered 5-FU 1.0 mg/m(2) with eniluracil given in a 10:1 ratio (eniluracil:5-FU) twice daily for the first 28 days of each 35-day cycle. RESULTS: Eighty-four patients were enrolled. Eight partial responses were observed in 84 patients (10%; 95% confidence interval [CI], 4.2% to 17.9%), and 20 patients (24%) had stable disease. The median duration of partial response was 20.1 weeks (95% CI, 12 to 26.7 weeks). The median duration of progression-free survival and overall survival for all patients was 9.9 weeks and 40.4 weeks, respectively. Most adverse events were grade 1 or 2 in intensity. Diarrhea, nausea, malaise/fatigue, vomiting, and mucositis were the most common treatment-related nonhematologic adverse events. The most frequently occurring grade 3 or 4 treatment-related adverse events were malaise/fatigue and diarrhea, occurring in 17% and 7% of patients, respectively. The incidence of grade 3 or 4 hematologic toxicity was low. Grade 3 or 4 hyperbilirubinemia occurred in 17% of patients. CONCLUSION: Eniluracil-5-FU has modest antitumor activity and an acceptable safety profile in anthracycline- and taxane-resistant breast cancer. Treatment was convenient, and patient compliance was high.

Administration, Oral↗
PubMed2002

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer.

PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.

Adult↗
PubMed2002

Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel.

PURPOSE: ABI-007 is a novel Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. The absence of Cremophor EL may permit ABI-007 to be administered without the premedications used routinely for the prevention of hypersensitivity reactions. Furthermore, this novel formulation permits a higher paclitaxel concentration in solution and, thus, a decreased infusion volume and time. This Phase I study examines the toxicity profile, maximum tolerated dose (MTD), and pharmacokinetics of ABI-007. EXPERIMENTAL DESIGN: ABI-007 was administered in the outpatient setting, as a 30-min infusion without premedications. Doses of ABI-007 ranged from 135 (level 0) to 375 mg/m2 (level 3). Sixteen patients participated in pharmacokinetic studies. RESULTS: Nineteen patients were treated. No acute hypersensitivity reactions were observed during the infusion period. Hematological toxicity was mild and not cumulative. Dose-limiting toxicity, which occurred in 3 of 6 patients treated at level 3 (375 mg/m2), consisted of sensory neuropathy (3 patients), stomatitis (2 patients), and superficial keratopathy (2 patients). The MTD was thus determined to be 300 mg/m2 (level 2). Pharmacokinetic analyses revealed paclitaxel C(max) and area under the curve(inf) values to increase linearly over the ABI-007 dose range of 135-300 mg/m2. C(max) and area under the curve(inf) values for individual patients correlated well with toxicity. CONCLUSIONS: ABI-007 offers several features of clinical interest, including rapid infusion rate, absence of requirement for premedication, and a high paclitaxel MTD. Our results provide support for Phase II trials to determine the antitumor activity of this drug.

Adult↗
PubMed2002

Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial.

PURPOSE: Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy. In this prospective randomized trial, the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer. EXPERIMENTAL DESIGN: Five hundred twenty-four patients were randomized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil, Adriamycin, and cyclophosphamide (Pac/FAC) or with 8 cycles of FAC alone. Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting. Planned duration of therapy was the same in all patients. After completion of 8 cycles of chemotherapy, those patients who were > or =50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years. RESULTS: Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5-89 months. Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group. The difference between the two groups was not statistically significant (P = 0.09). The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66. CONCLUSION: Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence; however, differences were not statistically significant. At the time of this analysis, there have been 47 deaths. The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Docetaxel secretion in tears: association with lacrimal drainage obstruction.

OBJECTIVE: To test the hypothesis that docetaxel may be secreted in tears after intravenous infusion. DESIGN: Prospective pilot trial. PATIENTS AND METHODS: Tear fluid was collected from 4 patients receiving docetaxel weekly and 2 patients receiving docetaxel every 3 weeks as a single agent for the treatment of metastatic breast cancer. Tear samples were collected once prior to and again within 30 minutes following the end of the 1-hour docetaxel infusion. A blood sample was also obtained after infusion. The tear and plasma samples were analyzed for drug content using high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Docetaxel was found in the tear samples collected from all 6 patients. CONCLUSION: The secretion of docetaxel in tears may be a mechanism for canalicular inflammation and tear drainage obstruction, which are known to occur as an adverse effect of the drug.

Aged↗
PubMed2002

A detailed evaluation of cardiac toxicity: a phase II study of doxorubicin and one- or three-hour-infusion paclitaxel in patients with metastatic breast cancer.

PURPOSE: This Phase II study was designed to determine the efficacy and toxicity of combination doxorubicin and paclitaxel as front-line treatment for metastatic breast cancer. EXPERIMENTAL DESIGN: Eligible patients had no prior anthracycline or taxane therapy and normal cardiac function. They were treated with bolus doxorubicin 60 mg/m2, followed by paclitaxel 200 mg/m2, as either 1- or 3-h infusions for six to seven cycles. Single-agent paclitaxel was continued thereafter. Serial multiple gated acquisition scans were performed, and endomyocardial biopsies were performed for consenting patients. RESULTS: Eighty-two patients were enrolled with a median age of 53 years (range, 32-78 years). Of 79 evaluable patients, 58.2% had an objective response (3.8% complete response + 54.4% partial response), 34.2% had stable disease, and 7.6% had progressive disease. With median follow-up of 37.5 months, median time to progression was 7 months; median survival was 31 months. Multiple gated acquisition scans were performed in 82 of 82 patients at baseline, 75 of 82 patients at a total doxorubicin dose of 60-180 mg/m2, 62 of 68 patients at 200-300 mg/m2, 18 of 52 patients at 310-360 mg/m2, and 4 of 8 patients at 420 mg/m2. Median ejection fractions were 62.5, 60, 57.5, 52.5, and 32%, respectively. Fifteen of 82 (18.3%) patients had a decrease in ejection fraction > or = 15% to an absolute ejection fraction < or = 50%. Eight of these 15 patients (53%) developed clinical congestive heart failure: 4 of 8 (50%) who received a total doxorubicin dose of 420 mg/m2 versus 4 of 74 (5.4%) who received a dose < or = 360 mg/m2 (P = 0.002). CONCLUSIONS: When the doxorubicin dose exceeds 360 mg/m2, the combination of bolus doxorubicin and paclitaxel presents unacceptable cardiac risk.

Adult↗
PubMed2001

Lack of activity of stealth liposomal doxorubicin in the treatment of patients with anthracycline-resistant breast cancer.

PURPOSE: We conducted a single-institution phase II clinical trial to determine the objective response rate, duration of response, time to progression, and overall survival in patients with anthracycline-resistant breast cancer treated with Doxil. PATIENTS AND METHODS: Patients with metastatic breast cancer were eligible if they had disease progression while receiving an anthracycline-containing regimen or developed evidence of metastatic disease during or within 6 months after the last cycle of an anthracycline-containing adjuvant regimen. Prior treatment with liposomal doxorubicin was not allowed. Patients received a dose of 50 mg/m(2) infused every 4 weeks via a peripheral vein or central line. Doxil was administered for a total of six cycles or until disease progression. RESULTS: We treated 11 patients with stage IV breast cancer of whom two had never received chemotherapy for their metastatic disease. Most had a performance status of 1 and had visceral involvement as their dominant site of disease. All patients had received prior therapy with doxorubicin. No clinical evidence of congestive heart failure or cardiac toxicity was observed. The most common toxicities were nonhematologic and were mostly grade 1/2. These included fatigue, nausea, vomiting, and stomatitis. Significant myelosuppression was only observed in one patient. No complete or partial response was observed. There were two patients who had a minimal response and two other patients who had evidence of stable disease. CONCLUSION: Doxil was well tolerated with minimal toxicity. However, the lack of antitumor activity in anthracycline-resistant breast cancer patients indicates that further evaluation in this patient population is not warranted.

Adult↗
PubMedDate not supplied

Outcomes and cost of deep venous thrombosis among patients with cancer.

BACKGROUND: Although deep venous thrombosis (DVT) often complicates the clinical course in patients with cancer, few studies of the outcomes of DVT in this population have been published. Furthermore, the cost of DVT is largely undescribed. We herein report the largest study of DVT in this population to date. METHODS: We reviewed the medical records of 529 consecutive cancer patients in whom DVT developed from January 1, 1994, through December 31, 1997, and followed up these patients through December 31, 2000, for outcomes. The cost of hospitalization was obtained from our hospital's cost-accounting system and inflated to 2002 US dollars using the Consumer Price Index for Medical Care. Logistic regression was used to identify factors that were associated with a high risk of poor outcomes. RESULTS: The most common complication of DVT was bleeding, which occurred in 13% of patients. Pulmonary embolus occurred in 4%. Five patients (1%) died of complications of DVT and 5 (1%) of complications of anticoagulation. Recurrence of DVT was common (17% overall), particularly among those who had inferior vena cava filters (32%; P<.001) or a previous episode of DVT (P =.03). All but 4 patients were hospitalized for initial anticoagulation therapy, for a mean of 11 days. The mean cost of hospitalization was 2002 US $20 065. CONCLUSIONS: Among patients with cancer, DVT frequently is associated with serious clinical outcomes. Its treatment is resource intensive and costly. More effective agents and less costly management strategies could have a significant impact on the outcomes and cost of DVT in this population.

Aged↗
PubMedDate not supplied

Fluorouracil, doxorubicin, and cyclophosphamide followed by tamoxifen as adjuvant treatment for patients with stage IV breast cancer with no evidence of disease.

We conducted a single-institution study to determine whether local therapy plus six cycles of chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) followed by 5 years of tamoxifen is superior to local treatment alone in terms of disease-free survival (DFS) and overall survival (OS) in patients with stage IV breast cancer with no evidence of disease (stage IV-NED breast cancer). Patients with breast cancer were eligible if they had histologic proof of a locoregional or distant recurrence that had been curatively resected, irradiated, or both and had no other evidence of disease. Patients who had received prior anthracycline therapy were not eligible. All patients received six cycles of intravenous FAC, with cycles repeated every 3 weeks. After completion of chemotherapy, patients whose tumors had not previously demonstrated resistance to tamoxifen and had positive or unknown estrogen receptor status received tamoxifen 20 mg by mouth daily for 5 years. Patients in this study were compared with a historical control population (patients with stage IV-NED breast cancer who never received systemic therapy) as well as with the patients in two previously reported trials of chemotherapy for stage IV-NED disease. Forty-seven patients were registered, but only 45 were evaluable. There was a highly statistically significant difference ( p < 0.001) in OS and DFS among the four groups, with patients in our most recent study having the best OS and DFS at 3 years compared with the control group (84% vs. 55% and 66% vs. 11%, respectively). When patients in all four groups were analyzed together in search of prognostic factors, we found that patients whose primary tumors had negative axillary lymph nodes had a statistically significant improvement in OS and DFS ( p < 0.01) compared with patients with positive axillary lymph nodes. No survival differences were found between patients with positive and those with negative hormone receptor status. This study demonstrates a benefit in terms of OS and DFS for patients with stage IV-NED breast cancer who receive doxorubicin-based adjuvant chemotherapy. The benefit was greater on patients with node-negative primary tumors. In patients with stage IV-NED disease, doxorubicin-based chemotherapy should be considered standard treatment after adequate local control is achieved.

Administration, Oral↗