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Biomedical subjects

V Valero

Publications and source records attributed to V Valero.

70 records · Page 4Linked to original sources
PubMed1996

Locally Advanced Breast Cancer.

Locally advanced breast cancer encompasses a heterogeneous collection of breast neoplasms and constitutes approximately 10%-20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. Patients with these tumors may be classified as stage IIB, III or IV breast cancer according to the American Joint Committee for Cancer Staging and End Results Reporting (TNM classification). Multidisciplinary therapy has become the treatment of choice for these patients. Primary or neoadjuvant chemotherapy followed by locoregional therapy, either surgery and/or radiotherapy, and postoperative systemic chemotherapy is now an accepted strategy. More than 70% of patients achieve an objective response (including pathological complete remission in 10%-25% of cases), and many patients experience downstaging through primary chemotherapy. Breast conservation is possible in 10%-40% of patients with locally advanced breast cancer; almost all patients initially are rendered disease-free, and long-term local control is achieved in over 70% of these patients. Primary chemotherapy is the initial choice of treatment for patients with locally advanced tumors, but it is unclear what the optimal sequence of subsequent therapies should be, whether one or two local treatment modalities are necessary, and whether any or different postoperative chemotherapy is needed. The efficacy of primary chemotherapy was demonstrated in several large prospective studies in patients with locally advanced breast cancer. The natural history of this disease was changed dramatically by the introduction of these combined modality therapies. Five-year disease-free survival rates of 35%-70% are commonly reported, and about 25%-40% of patients will survive beyond 10 years without recurrence. In summary, multidisciplinary therapy that includes primary chemotherapy provides appropriate local control and the possibility of breast conservation therapy; it increases surgical resectability and survival rates in patients with locally advanced breast cancer. The role of new innovative therapeutic strategies such as high-dose chemotherapy, with hematopoietic stem cell rescue, new cytotoxic agents and higher dose-intensity therapy is currently under evaluation in patients with locally advanced breast cancer.

Journal Article↗
PubMed1996

Treatment of patients resistant to paclitaxel therapy.

Although the taxoid drugs, paclitaxel (Taxol) and docetaxel (Taxotere) have a broadly similar mechanism of action, there are notable differences in their activities and they are distinct agents. Docetaxel is more potent than paclitaxel with regard to the promotion of the polymerization of tubulin and the inhibition of depolymerization, and has greater antitumour activity in many in vitro and in vivo tumour model systems. The development of drug resistance is a major problem in the treatment of metastatic breast cancer and observations indicating only partial cross-resistance between docetaxel and paclitaxel in vitro, combined with supporting clinical evidence of activity in patients with previously-treated tumours, including anthracycline-resistant breast cancer, led to the implementation of a prospective study of docetaxel treatment in patients with paclitaxel-resistant disease. Preliminary results in 27 patients recruited to this ongoing study indicate that docetaxel has activity in paclitaxel-resistant metastatic breast cancer.

Adult↗
PubMed1995

Phase I clinical and pharmacological study of suppression of human antimouse antibody response to monoclonal antibody L6 by deoxyspergualin.

Development of human antimouse antibody (HAMA) is a major limiting factor in the application of murine mAb for clinical use. A novel immunomodulatory drug, deoxyspergualin (DSG), has shown potential to suppress antimouse antibody response in preclinical model systems. We conducted a Phase I trial to determine the effect of DSG on HAMA response to murine mAb L6 administered to patients with advanced cancers (in previous trials, this antibody elicited HAMA in two-thirds of the treated patients). L6 mAb was administered at a fixed dose of 200 mg/m2 on days 1-5. DSG was administered at doses of 50 mg/m2 [dose level (dl) 1] or 150 mg/m2 (dls II and III) on days 1-7. Treatment courses were repeated every 6 weeks (dls I and II) or every 3 weeks (dl III). HAMAs were quantitated by a commercially available ELISA assay (ImmuSTRIP; anti-isotypic antibodies) and a radiometric assay (antiisotypic and anti-idiotypic antibodies). Pharmacokinetics of L6 and DSG was also studied in all consenting patients. Among 24 evaluable patients, 2 patients developed detectable HAMAs using the ELISA (one each at dls I and II) after a median follow-up of 122 days (P = 0.0001 as compared to historical controls). Even in the two patients who developed HAMA, the HAMA levels were quite low (160 and 181 ng/ml; historical experience, 70-38,744 ng/ml). The radiometric assay detected anti-L6 antibodies in 13 patients (4, 6, and 3 at dls I-III, respectively) after a median of 82 days. The median highest anti-L6 antibody level was 129 ng/ml (range, 21-2150). The highest anti-L6 antibody level at dl III was only 44 ng/ml. The results suggest suppression of anti-idiotypic response also. No clinical antitumor activity was observed, and no significant changes in T4/T8 subsets or immunoglobulins occurred (suggesting a lack of generalized immunosuppression). We conclude that DSG can suppress HAMA response to L6. A starting dose of 150 mg/m2/day is recommended for Phase II trials to confirm this observation.

Adult↗
PubMed1995

Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.

PURPOSE: To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.

Adult↗
PubMed1995

Review of docetaxel (Taxotere), a highly active new agent for the treatment of metastatic breast cancer.

Phase II studies have demonstrated that docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) is one of the most active single agents in the treatment of metastatic breast cancer. The overall response rate as front-line therapy for metastatic disease was 59% (95% confidence interval, 51% to 67%) in five phase II trials (four of which were multicenter) when 100 mg/m2 docetaxel was infused over 1 hour every 3 weeks. In the three phase II trials reported to date of patients with metastatic cancer who had failed previous frontline therapy, 100 mg/m2 docetaxel infused over 1 hour every 3 weeks produced an objective response rate of 49% (95% confidence interval, 40% to 58%). Two of these trials specifically included patients who had progressed while receiving either an anthracycline or an anthracenedione; the overall response rate in this subset of 83 patients was 48%. The most significant acute toxicity noted in these trials was neutropenia. Grade 4 neutropenia occurred in the majority of patients but rarely resulted in treatment delays. Hypersensitivity reactions also were common in nonpremedicated patients, but were rare after the institution of premedication with antihistamines and/or glucocorticoids. A novel toxicity observed in many patients was fluid retention syndrome, with onset at a median of four to five cycles. The fluid retention was of noncardiac or renal origin, was slowly progressive with additional cycles of therapy, was reversible after cessation of the drug, and could be largely ameliorated by oral diuretics and glucocorticoid premedication. Phase III studies to further define docetaxel's role in the treatment of breast cancer are now under way.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Phase II study of deoxyspergualin in metastatic breast cancer.

We conducted a phase II trial of the novel immunomodulatory/cytotoxic agent 15-deoxyspergualin in patients with metastatic breast cancer who had failed treatment with front-line chemotherapy. Thirty-eight courses of treatment were administered to fourteen patients enrolled in this trial, 25 at a dose of 1800 mg/m2/d (dose level 0) and 13 at a dose of 2150 mg/m2/d (dose level +1) administered by continuous intravenous infusion for 5 days. Treatment was well tolerated with neuromuscular side-effects (myalgias, paresthesias) and granulocytopenia (nadir granulocyte count of 0.50-0.99 x 10(9)/l) in two and three courses, respectively, as the only grade III toxicities. The neuromuscular toxicity of deoxyspergualin is probably related to the occurrence of hypomagnesemia. No partial or complete responses were observed in this study. One patient achieved a minor response but had progressive disease 65 weeks after enrollment. The response was observed coincident with an increase in T4/T8 ratio in the peripheral blood. The median time to progression for the entire cohort was eight weeks (range, 4-65 weeks). There was no clinical evidence of immunosuppression and no decrease in total peripheral blood lymphocyte counts or helper T-cells was observed. At the doses and schedule employed in this trial, deoxyspergualin does not appear to have significant activity against metastatic breast cancer resistant to front-line chemotherapy. The correlation between hypomagnesemia and neuromuscular toxicity of deoxyspergualin is an intriguing, previously unknown observation and requires further investigation.

Adult↗
PubMed1994

Bioequivalence of 20-mg once-daily tamoxifen relative to 10-mg twice-daily tamoxifen regimens for breast cancer.

PURPOSE: We studied the bioequivalence of a new once-daily regimen of tamoxifen citrate relative to the standard twice-daily regimen of tamoxifen citrate, an established antiestrogenic treatment for breast cancer. PATIENTS AND METHODS: Of 30 women with breast cancer, 27 completed this open, two-period, crossover randomized trial. During one 3-month period, patients took one standard 10-mg tamoxifen tablet twice daily; during the preceding or following 3-month period, patients took one of the new 20-mg tablets once daily. Pharmacokinetic profiles and safety parameters were assessed at the end of each 3-month treatment period. RESULTS: Overall, measured concentrations of tamoxifen and its principal active metabolite, N-desmethyltamoxifen, remained relatively constant over the 24-hour sampling periods at the end of each treatment sequence. For both compounds, the percentage differences of the geometric means for all pharmacokinetic parameters indicated bioequivalence of the once-daily regimen of tamoxifen relative to the standard twice-daily regimen. Both treatment sequences were well tolerated; reported adverse events occurred at similar frequencies with the two treatment regimens. CONCLUSION: The 20-mg tamoxifen tablet taken once daily was bioequivalent to the 10-mg tamoxifen tablet taken twice daily, with no difference in relative risk. The once-daily treatment is a simpler regimen and may facilitate compliance, which may enhance therapeutic outcomes during long-term treatment of breast cancer.

Administration, Oral↗
PubMed1993

The M. D. Anderson Cancer Center experience with Taxol in metastatic breast cancer.

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)

Adult↗
PubMed1992

The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity.

This paper reports the results of the first field study performed to assess the safety, immunogenicity and protectivity of the synthetic malaria vaccine SPf66 directed against the asexual blood stages of Plasmodium falciparum. Clinical and laboratory tests were performed on all volunteers prior to and after each immunization, demonstrating that no detectable alteration was induced by the immunization process. The vaccines were grouped as high, intermediate or low responders according to their antibody titres directed against the SPf66 molecule. Two of the 185 (1.08%) SPf66-vaccinated and nine of the 214 (4.20%) placebo-vaccinated volunteers developed P. falciparum malaria. The efficacy of the vaccine was calculated as 82.3% against P. falciparum and 60.6% against Plasmodium vivax.

Amino Acid Sequence↗
PubMed1991

Genetic control of the immune response to a synthetic vaccine against Plasmodium falciparum.

Two independent vaccination trials using a hybrid synthetic polypeptide containing epitopes from four proteins of Plasmodium falciparum were performed. In the first trial 63 and in the second 122 volunteers were vaccinated, using different immunization schedules. The analysis of the humoral response to the vaccine, measured by IgG antibody titres to the polypeptide showed a bimodal distribution in both cases suggesting genetic control of the immune response to this protein. There was a small group of low or non-responders and a large group of good responders. HLA phenotyping of the two groups disclosed an association of the low responders to HLA-DR4 antigens with chi-square P value of 0.00039 when compared with the good responders group. These findings provide evidence for the genetic control of the immune response to the synthetic vaccine by the association of this response with particular alleles of the HLA class II antigens; such findings may lead to an explanation of the mechanism involved in disease susceptibility and need to be used in the design of a totally effective vaccine.

Adolescent↗
PubMed1985

Liver abscess complicating Crohn's disease presenting as thoracic empyema. Case report and review of the literature.

A 28-year-old man with a history of Crohn's disease presented with right pleuritic pain and dyspnea. Chest radiography showed a right pleural effusion. Thoracocentesis yielded purulent fluid that subsequently grew Enterobacter aerogenes. Computed axial tomography of the abdomen revealed right subphrenic abscess and right hepatic lobe abscess. Antibiotic therapy and surgical drainage resulted in complete recovery. A review of the English literature produced 18 cases of liver abscess complicating Crohn's disease. Details of 14 of these cases are summarized.

Adult↗
PubMedDate not supplied

Salmonella focal intracranial infections: review of the world literature (1884-1984) and report of an unusual case.

Focal intracranial infections are unusual manifestations of salmonellosis. Forty-three such infections have been reported in the world literature. The clinical data for 34 well-documented cases are reviewed. Eleven patients had brain abscess, 19 had subdural empyema, three had epidural abscess, and one had both subdural empyema and brain abscess. Brain abscess occurred more often in adults; in contrast, subdural empyema presented more often in children. Fever, signs and symptoms of increased intracranial pressure, change in mental status, seizures, and focal neurologic deficits were the commonest clinical features. Salmonella serotypes typhi, typhimurium, and enteritidis occurred most frequently. The precipitating factors of these infections included meningitis, trauma, and intracranial hematoma. Surgical drainage combined with systemic antibiotic therapy resulted in the recovery of 21 of 25 patients. A case of embryonal carcinoma plus seminoma of the testis with brain metastases complicated by a salmonella brain abscess is also reported. This is the first report in the world literature of a focal salmonella infection in a neoplastic lesion within the central nervous system.

Adolescent↗
PubMedDate not supplied

Factors predictive of outcome in patients with breast cancer refractory to neoadjuvant chemotherapy.

PURPOSE: The purpose of this study was to determine the clinical, pathological, and treatment factors that are predictive of local-regional recurrence and overall survival for patients with breast cancer that is refractory to neoadjuvant chemotherapy. PATIENTS AND METHODS: This study analyzed the data of the 177 breast cancer patients treated on our institutional protocols who had less than a partial response to neoadjuvant chemotherapy. The initial clinical stage of disease was II in 27%, III in 69%, and IV (supraclavicular lymph node involvement) in 4%. Surgery was performed in 94% of the patients, and 77% of these patients also received adjuvant chemotherapy. RESULTS: After a median follow-up of 5.2 years, 106 patients experienced disease recurrence, with 98 of these having distant metastases and 45 having local-regional recurrence. The 5- and 10-year overall survivals for the entire group were 56% and 33%, respectively. The factors that were independently associated with a statistically significant poorer overall survival in a Cox regression analysis were pathologically involved lymph nodes after surgery, estrogen receptor-negative disease, and progressive disease during neoadjuvant chemotherapy. The 5-year overall survival for patients with pathologically negative lymph nodes ranged from 84% (estrogen receptor-positive disease) to 75% (estrogen re-ceptor-negative disease), compared with rates for patients with pathologically positive lymph nodes of 66% (estrogen receptor-positive disease) and 40% (estrogen receptor-negative disease). The 5-year survival of patients with progressive disease was only 19%. The 5- and 10-year local-regional recurrence rates for the 177 patients were 27% and 34%, respectively. Significant factors on Cox analysis that predicted for local-regional recurrence were four or more pathologically involved lymph nodes and estrogen receptor-negative disease. For the 105 patients treated with surgery and postoperative radiation therapy, the 10-year local-regional recurrence rates for the subgroups with 0, 1, or 2 of these factors were 12%, 25%, and 44%, respectively. CONCLUSIONS: For patients with a poor response to neoadjuvant chemotherapy, conventional treatments achieve reasonable outcomes in those with lymph node-negative disease or estrogen receptor-positive disease. However, more active systemic and local therapies are needed for patients with estrogen receptor-negative disease and positive lymph nodes and for those with clinical evidence of progressive disease during neoadjuvant chemotherapy.

Adult↗
PubMedDate not supplied

A study of aspirin induced changes in bleeding time, platelet aggregation, and Sonoclot coagulation analysis in humans.

The purpose of this study was to determine whether or not a newer test of platelet function, Sonoclot coagulation analysis, can identify the patients who develop significant prolongation of bleeding time after aspirin ingestion. Template bleeding time, platelet aggregation in response to arachidonic acid, collagen, epinephrine, adenosine diphosphate, and ristocetin, and Sonoclot coagulation analysis were performed before and after ingestion of aspirin in 22 adult volunteers. Mean bleeding time increased from 5.32 +/- 2.16 min to 7.34 +/- 2.1 min, but remained within normal range (2.5 to 9 min). There was marked intersubject variability in the effect of aspirin on bleeding time, and difference between men and women was not significant. There was significant decrease in platelet aggregation in response to arachidonic acid, collagen and epinephrine. Sonoclot coagulation analysis did not show significant effect of aspirin administration. There was no correlation among changes in bleeding time, platelet aggregation, and Sonoclot coagulation analysis. Five patients with known platelet function disorders and prolonged bleeding times (mean = 18.5 min, range 14 to 22) without any other coagulation abnormalities were also studied. In four of these patients who had normal platelet count, Sonoclot graphs were morphologically similar to those in the volunteers with normal bleeding times, but in one patient with thrombocytopenia, morphology was altered. It is our conclusion that Sonoclot coagulation analysis is unlikely to identify patients with prolonged bleeding time in whom platelet count and other coagulation factors are normal.

Adult↗