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Biomedical subjects

V Valero

Publications and source records attributed to V Valero.

At least 55 records · Page 3Linked to original sources
PubMed1998

Hand-foot syndrome following prolonged infusion of high doses of vinorelbine.

BACKGROUND: The authors reviewed the incidence of toxic skin reactions in patients with metastatic breast carcinoma (MBC) treated with vinorelbine as a continuous infusion. METHODS: A Phase I/II protocol was designed in which vinorelbine was given as an 8-mg intravenous bolus followed by a 96-hour CI of 7-14 mg/m2/day. Sixty patients were enrolled in the study: all had MBC and had received prior chemotherapy, and they had no known dermatologic disorder. RESULTS: Hand-foot syndrome (HFS) developed in 4 of the 60 patients. Patient 1 started with vinorelbine at 12 mg/m2/day. She developed typical HFS. In the second course, her dose was decreased to 11 mg/m2/day, but again she experienced HFS. In the third course, dexamethasone was added to the regimen, and no HFS was observed in the remaining six courses. Patient 2 started with a dose of 9 mg/m2/ day. She received four courses without complications; but when the vinorelbine dose was escalated to 10 mg/m2/day, HFS developed. Patient 3 started with a vinorelbine dose of 14 mg/m2/day. She developed mucositis during the first two courses and HFS during the third. Patient 4 received vinorelbine at a dose of 13 mg/m2/day and developed significant HFS. All patients had complete dermatologic recovery. No toxic skin reactions were observed in 14 patients receiving vinorelbine doses of <10 mg/m2/day, whereas 4 of 46 treated at 10-14 mg/m2/day developed HFS, suggesting a relationship of dose to HFS occurrence. CONCLUSIONS: Longer infusions of vinorelbine are occasionally associated with HFS. The pathophysiology is not completely clear, but a relationship of HFS occurrence to dose is suggested. Steroids were effective as prophylaxis in one patient.

Adult↗
PubMed1998

Clinical course of breast cancer patients with metastases confined to the lungs treated with chemotherapy. The University of Texas M.D. Anderson Cancer Center experience and review of the literature.

PURPOSE: To evaluate the clinical course of patients with a metastatic breast cancer (MBC) confined to the lungs and treated with doxorubicin/cyclophosphamide-containing chemotherapy (DC-CT). PATIENTS AND METHODS: Between 1973 and 1985, 1581 patients with MBC were treated with DC-CT at M.D. Anderson Cancer Center. Data for 88 patients (5.6%) with metastases confined to the lungs were reviewed to correlate various clinical characteristics with response to treatment and survival. RESULTS: The overall response rate was 76% with 33% achieving complete response (CR). The median overall survival time was 22 months (range 1-210). The 10-year survival rate was 9%. The overall response and CR rates were higher for the patients with metastases confined to the lungs (76% and 33%. respectively) than for the remainder of MBC patients (64% and 14%; P < 0.01). The 10-year survival rate was also higher (9% versus 3%, P < 0.01), but there were no differences in median overall survival rate. CONCLUSIONS: This retrospective analysis demonstrated that patients with metastases confined to the lungs treated with DC-CT had a high objective response rate, especially high CR rates, and a median survival comparable to that of our entire population of MBC patients. A small but clinically significant percentage of patients had prolonged survival. Therefore, not all visceral sites are indicators of poor prognosis.

Adult↗
PubMed1998

Phase II study of ifosfamide and mesna in patients with metastatic breast cancer.

The aim of this paper is to evaluate the activity of ifosfamide in previously treated patients with metastatic breast cancer. From June 1991 through November 1992, 29 patients with metastatic breast cancer were treated with single-agent ifosfamide, 2 g/m2 intravenously daily for 5 days, with mesna support. All patients had previously received chemotherapy; all but one had previously received cyclophosphamide. The ifosfamide-mesna regimen was the first-line metastatic regimen in 15 patients, the second-line metastatic regimen in 13 patients, and the third-line metastatic regimen in one patient. Two partial remissions (7%) were observed; both occurred in the first-line metastatic group. The partial remissions were noted in patients who had completed adjuvant cyclophosphamide therapy 60 and 91 months earlier. Both responses were seen in lung metastases. The response durations were 5 and 8 months on continued therapy. The main adverse effects were granulocytopenia, fatigue, nausea, vomiting, and stomatitis. At the dose used in this study, ifosfamide and mesna given without growth-factor support resulted in significant myelosuppression and produced only two partial remissions (7%) in 29 patients. Further study of ifosfamide as an isolated agent in previously treated patients is not warranted.

Adult↗
PubMed1998

Daily oral etoposide in patients with heavily pretreated metastatic breast cancer.

The objective of this phase II study was to evaluate the activity and toxicity of oral etoposide (50 mg/m2 daily for 21 days in 28-day cycles) in patients with heavily pretreated metastatic breast cancer. Thirty patients were entered into the study; all had clinical or radiologic evidence of disease progression, median age was 51 years, and the majority of patients (82%) had a Zubrod performance status equal to or lower than 1 and a median of 3 disease sites. All patients had received chemotherapy, and more than 80% had received 3 or more regimens. More than 70% of the patients had received taxanes as one of their previous therapies. Twenty-four and 28 patients were evaluable for tumor response and toxicity, respectively. One partial response was seen (<4%), and seven patients (25%) demonstrated stable disease with a median duration of four months. There was significant hematologic toxicity. In two patients therapy had to be stopped because of excessive toxicity, and five patients required hospitalization for neutropenic fever. Overall, 57% of patients experienced grade 2 or higher degree of neutropenia including two patients with grade 4 toxicity. Seventeen percent of patients developed grade 2 or greater thrombocytopenia, including one patient who experienced grade 4 toxicity, and 71% of the patients had grade 2 or more severe anemia including two patients with grade 4 toxicity. Oral etoposide has limited activity as third- or fourth-line agent and produces significant hematologic toxicity in patients with heavily pretreated metastatic breast cancer.

Administration, Oral↗
PubMed1998

Docetaxel and cyclophosphamide induced remission in platinum and paclitaxel refractory ovarian cancer.

Platinum-based chemotherapy is the standard treatment for advanced ovarian cancer, with response rates of 40-60%. In patients who fail platinum treatment, paclitaxel has resulted in response rates of 10-48%. Docetaxel has partial non-cross-resistance with and is twice as potent in vitro as paclitaxel in inhibiting microtubule disaggregation. The combination of docetaxel and cyclophosphamide is synergistic in pre-clinical studies and clinically active in breast cancer. We present the case of a patient with platinum and paclitaxel refractory ovarian cancer who achieved a remission with docetaxel and cyclophosphamide.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer.

PURPOSE: The population pharmacokinetic/pharmacodynamic (PK/PD) approach was prospectively integrated in the clinical development of docetaxel to assess the PK profile in a large population of patients and investigate systemic exposure as a prognostic factor for clinical outcome. PATIENTS AND METHODS: PK analysis was performed at first course in 24 phase II studies of docetaxel monotherapy using four randomized limited-sampling schedules. Bayesian estimates of clearance (CL), area under the concentration-time curve (AUC), and peak and duration of plasma levels greater than threshold levels were used as measures of exposure. PD data included for efficacy, response rate, time to first response, and time to progression (TTP) in breast cancer and non-small-cell lung cancer (NSCLC), and for toxicity, grade 4 neutropenia, and febrile neutropenia at first course and time to onset of fluid retention. PK/PD analysis was conducted using logistic and Cox multivariate regression models. RESULTS: PK protocol implementation was successful. Most of the patients registered (721 of 936, 77%) were sampled and 68% were assessable for PK (640 patients). First-course docetaxel AUC was a significant predictor (P = .0232) of TTP in NSCLC (n = 151). Docetaxel CL was a strong independent predictor (P < .0001) of both grade 4 neutropenia and febrile neutropenia (n = 582). Cumulative dose was the strongest predictor (P < .0001) of the time to onset of fluid retention (n = 631). However, the duration of exposure over 0.20 micromol/L (0.16 microg/mL) at first course was an independent predictor (P = .0029). Few patients (n = 25, 4%) received the recommended dexamethasone premedication. CONCLUSION: First-course docetaxel PK is a predictor of first-course hematologic toxicity, but also of fluid retention, which is cumulative in nature. Patients with elevated hepatic enzymes have a 27% reduction in docetaxel CL and are at a higher risk of toxicity. A starting dose of 75 mg/m2 is currently being evaluated in this population. Prospective implementation of large-scale population PK/PD evaluation is feasible in early drug development and this approach generates clinically relevant findings.

Adult↗
PubMed1998

A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer.

PURPOSE: To evaluate the efficacy and safety of docetaxel in patients with paclitaxel-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered at four centers. Patients had previously received < or = two chemotherapy regimens for MBC. All patients had progressive disease while receiving paclitaxel therapy. Treatment was repeated until there was evidence of disease progression or for a maximum of three cycles after best response. RESULTS: Objective responses were seen in eight of 44 assessable patients (18.1%; 95% confidence interval [CI], 6.7% to 29.5%). Seven patients had partial responses and one patient responded completely. Response rates were not significantly different by previously received paclitaxel dose or resistance. No responses were seen in 12 patients who had previously received paclitaxel by 24-hour infusion, but the response rate in 32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The median response duration was 29 weeks and the median time to disease progression was 10 weeks. Median survival was 10.5 months. Clinically significant (severe) adverse events included neutropenic fever (24% of patients), asthenia (22%), infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and diarrhea (7%). CONCLUSION: Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.

Adult↗
PubMed1998

[Neurotransmitter release: a process of membrane fusion occurring in fractions of milliseconds].

INTRODUCTION: The physiological mechanisms involved in neurotransmitter release were established thanks to the pioneer work of Katz, Del Castillo and Miledi at the neuromuscular junction. They termed their work as the quantal hypothesis of synaptic transmission. This hypothesis was further established morphologically by the work of Heuser and Reese. However, the molecular events underlying this process are poorly understood. We are starting to know which proteins interact between the vesicle and plasma membrane to promote fusion and to identify which molecules participate in the sensing of cytosolic calcium. DEVELOPMENT: Thanks to the combination of molecular biology, electrophysiology and microfluorometry, a huge amount of new information is been obtained on the mechanisms participating in synaptic transmission. This data deals with processes concerning to different pools of synaptic vesicles and their availability to reach the presynaptic membrane; the molecular events responsible for the targeting of these vesicles with the plasma membrane; the sensitivity to calcium at the presynaptic membrane; the fusion of membranes required to release the vesicle contents, and the mechanisms responsible for membrane retrieval needed for presynaptic homeostasis. CONCLUSIONS: In this review we discuss new data regarding synaptic function. However, some key points are still a matter of controversy. Meanwhile the quantal hypothesis is valid, the precise processes by which channels and vesicles interact, membrane is recycled and vesicles reused are still controversial. New techniques should be developed to address these points.

Calcium Channels↗
PubMed1997

Docetaxel and cyclophosphamide in patients with advanced solid tumors.

This trial was designed to determine the recommended maximum tolerated dose (MTD), toxicity, pharmacokinetics, and efficacy of docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) for phase II studies. Both drugs were administered to 39 patients with advanced solid tumors, 26 of whom had breast cancer. Docetaxel doses ranged from 60 to 85 mg/m2 and cyclophosphamide doses ranged from 600 to 800 mg/m2. All patients received steroid prophylaxis. The MTDs for patients with a history of prior chemotherapy were 75 mg/m2 of docetaxel and 700 mg/m2 of cyclophosphamide. For patients with no prior chemotherapy, the MTDs were 75 mg/m2 of docetaxel and 800 mg/m2 of cyclophosphamide. The dose-limiting toxicity was neutropenic fever, observed in 41% of patients and 13% of cycles. Addition of granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) did not permit further dose escalation, although it did result in briefer periods of neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Docetaxel as single-agent therapy in metastatic breast cancer: clinical efficacy.

The potential importance of docetaxel as a chemotherapeutic agent for the treatment of metastatic breast cancer has been documented in approximately 575 patients enrolled in phase II clinical studies in North America, Europe, and Japan. First-line treatment with docetaxel 100 mg/m2 intravenously over 1 hour every 3 weeks produced objective responses in 59% of patients (intent-to-treat). In patients with anthracycline-resistant disease (disease that responded initially but then progressed or relapsed during treatment with an anthracycline), an overall intent-to-treat response rate of 41% was achieved. A 37% response rate was observed in anthracycline-refractory patients (those who had never achieved an objective response to anthracycline-based chemotherapy). Febrile neutropenia is the major dose-limiting toxicity of docetaxel; the neutropenia nadir typically has an early onset and short duration, with rapid recovery of the neutrophil count. Other hematologic effects are rare. Skin and hypersensitivity reactions can be minimized by premedication with corticosteroids. Reversible fluid retention, related to the cumulative dose of docetaxel, is also lessened by corticosteroid prophylaxis. In summary, docetaxel has shown impressive antitumor activity in the treatment of metastatic breast cancer, including the challenging population of patients whose disease progressed during treatment with an anthracycline or anthracenedione. Most of the adverse events related to docetaxel use can be circumvented or ameliorated by careful patient selection and routine premedication with corticosteroids, and improved methods of managing side effects are being actively studied. Docetaxel is thus expected to play an increasingly prominent role in the management of patients with metastatic breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Combination docetaxel/cyclophosphamide in patients with advanced solid tumors.

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).

Adenocarcinoma↗
PubMed1997

Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer.

Relapse following complete remission achieved with a single course of high-dose chemotherapy continues to be the main cause of treatment failure in patients with metastatic breast cancer. A phase I/II trial was initiated that combined the two most active drugs against breast cancer, doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with cyclophosphamide, and delivered four cycles of these drugs with peripheral blood progenitor cells (PBPCs) and granulocyte colony-stimulating factor support in an outpatient setting. Patients with untreated metastatic breast cancer received two cycles of doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2. During recovery from the second cycle, PBPCs were harvested. Responding patients were then admitted for a day to receive escalating-dose doxorubicin, paclitaxel, and cyclophosphamide followed by PBPC reinfusion on day 3 as outpatients. Seventeen patients have been enrolled to date. Ten patients completed treatment and received 34 cycles of high-dose chemotherapy every 21 days (range, 21 to 28 days). The median age was 47 years (range, 26 to 56 years) and the median number of metastatic sites was two (range, one to three). Five patients had received adjuvant chemotherapy (four cyclophosphamide/methotrexate/5-fluorouracil and one mitoxantrone-based). The most common toxic reactions were nausea and vomiting (75% of courses) and neurosensory (50% of courses). No patients had a decreased ejection fraction or overt congestive heart failure. Ten patients underwent cardiac biopsy (median doxorubicin, 253 mg/m2; range, 120 to 312 mg/m2); only one showed grade 1 cytotoxic changes with doxorubicin 240 mg/ m2. Six patients were admitted for neutropenic fever. Eight of 10 patients responded (two pathologically confirmed complete remissions in liver). At these doses, four cycles of doxorubicin, paclitaxel, and cyclophosphamide with PBPC and granulocyte colony-stimulating factor support every 21 days was well tolerated and showed evidence of activity. Enrollment at higher dose levels continues so that maximum tolerated dose can be defined.

Adult↗
PubMed1996

A randomized trial of minoxidil in chemotherapy-induced alopecia.

BACKGROUND: Hair loss is a side effect of many chemotherapeutic agents, and patients have even refused possibly palliative or lifesaving drugs because they could not accept temporary or prolonged baldness. Topical minoxidil has been shown to be effective for androgenetic alopecia and alopecia areata. OBJECTIVE: Our purpose was to investigate the value and safety of minoxidil in chemotherapy-induced hair loss. METHODS: Twenty-two women who were facing adjuvant chemotherapy after breast surgery were registered in a protocol that used a 2% minoxidil topical solution or a placebo in a randomized double-blind trial. RESULTS: There was a statistically significant difference (favoring minoxidil) in the interval from maximal hair loss to first regrowth. Thus the period of baldness was shortened (mean, 50.2 days) in the minoxidil group. CONCLUSION: Minoxidil decreased the duration of alopecia caused by chemotherapy. There were no significant side effects.

Administration, Cutaneous↗
PubMed1996

Sequence-dependent alteration of doxorubicin pharmacokinetics by paclitaxel in a phase I study of paclitaxel and doxorubicin in patients with metastatic breast cancer.

PURPOSE: To determine whether a schedule-dependent interaction occurs when paclitaxel and doxorubicin are administered sequentially. PATIENTS AND METHODS: Ten patients with metastatic breast cancer received paclitaxel 125 mg/m2 over 24 hours either immediately before or after doxorubicin 48 mg/m2 over 48 hours as the initial chemotherapy treatment. Two such courses were given, and the sequence of administration was reversed after course 1. In cohort 1, paclitaxel preceded doxorubicin for course 1. In cohort 2, doxorubicin preceded paclitaxel for course 1. Doxorubicin levels were measured serially during the infusion and for 24 hours following it. Patients were assessed clinically for the occurrence of stomatitis and infection and granulocyte counts were measured twice weekly. RESULTS: Eight patients had complete pharmacokinetic sampling for both courses. The mean end-of-infusion plasma doxorubicin concentrations (Cmax) were 70% higher in the paclitaxel-doxorubicin sequence compared with the reverse sequence (45 +/- 8 ng/mL v 26 +/- 5 ng/ mL). The mean doxorubicin clearance was 32% lower in the paclitaxel-doxorubicin sequence (34.3 +/- 10.3 L/h v 51.6 +/- 16.1 L/h, P < .01). Clinically, hematologic and mucosal toxic effects were worse in the paclitaxel-doxorubicin sequence. The median absolute granulocyte count was 0.2/microL in the paclitaxel-doxorubicin sequence and 1.3/microL in the doxorubicin-paclitaxel sequence. Seven of 10 patients who received the paclitaxel-doxorubicin sequence had grade 2 (n = 4) or 3 (n = 3) stomatitis, while only one of 10 patients who received the doxorubicin-paclitaxel sequence had grade 2 stomatitis and none had grade 3. CONCLUSION: When paclitaxel by 24-hour infusion precedes doxorubicin by 48-hour infusion, doxorubicin clearance is reduced by nearly one third, which results in grade 2 and 3 stomatitis. To prevent this effect when paclitaxel (by 24-hour infusion) and doxorubicin are administered sequentially, doxorubicin should be given first. The mechanisms for this effect are under investigation.

Adult↗