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V Llorens

Publications and source records attributed to V Llorens.

17 recordsLinked to original sources
PubMed2001

A phase I and pharmacologic study of 9-aminocamptothecin administered as a 120-h infusion weekly to adult cancer patients.

PURPOSE: To define the toxicity profile and the recommended phase II doses of 9-aminocamptothecin (9-AC) administered as a weekly 120-h infusion. METHODS: 9-AC was administered over 120 h weekly to 55 adult cancer patients with solid tumors over doses ranging from 0.41 to 0.77 mg/m2 per day in a phase I and pharmacologic study. 9-AC formulated in dimethylacetamide/polyethylene glycol (DMA) was administered on a 3 of 4-week schedule, and the newer colloidal dispersion (CD) formulation was given on a 2 of 3-week schedule. RESULTS: Overall, 193 courses of therapy were administered over 122 dose levels. On the 3 of 4-week schedule, 9-AC DMA infused at > or = 0.6 mg/m2 per day for 120 h weekly produced dose-limiting neutropenia, thrombocytopenia, and diarrhea, or resulted in 1-2-week treatment delays. Shortening treatments to 2 of 3 weeks resulted in dose-limiting neutropenia and fatigue at infusion rates > 0.72 mg/m2 per day. The ratio of 9-AC lactone to total (carboxylate + lactone) drug plasma concentrations at steady-state was 0.15 +/- 0.07. Clinical toxicities and drug pharmacokinetics were not substantially different between the DMA and CD formulations. One objective response was observed in a patient with bladder cancer and minor responses were observed in patients with lung and colon cancers. Plasma area under the concentration versus time curve for 9-AC lactone modestly correlated with the degree of thrombocytopenia (r=0.51) using a sigmoid Emax pharmacodynamic model. CONCLUSION: The recommended phase II dose for the 9-AC DMA formulation is 0.48 mg/m2 per h over 120 h for 3 of 4 weeks and for the 9-AC CD formulation is 0.6 mg/m2 per day over 120 h for 2 of 3 weeks. Both regimens were well tolerated and feasible to administer.

Adult↗
PubMed2000

Phase I and pharmacologic study of irinotecan administered as a 96-hour infusion weekly to adult cancer patients.

PURPOSE: We conducted a phase I and pharmacologic study of a weekly 96-hour infusion of irinotecan to determine the maximum-tolerated dose, define the toxicity profile, and characterize the clinical pharmacology of irinotecan and its metabolites. PATIENTS AND METHODS: In 26 adult patients with solid tumors, the duration and dose rate of infusion were escalated in new patients until toxicity was observed. RESULTS: In 11 patients who were treated with irinotecan at 12.5 mg/m(2)/d for 4 days weekly for 2 of 3 weeks, dose-limiting grade 3 diarrhea occurred in three patients and grade 3 thrombocytopenia occurred in two patients. The recommended phase II dose is 10 mg/m(2)/d for 4 days given weekly for 2 of 3 weeks. At this dose, the steady-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +/- 1.10 nmol/L, and the Css of total irinotecan was 28.60 +/- 17.78 nmol/L. No patient experienced grade 3 or 4 neutropenia during any cycle. All other toxicities were mild to moderate. The systemic exposure to SN-38 relative to irinotecan was greater than anticipated, with a molar ratio of the area under the concentration curve (AUC) of SN-38 to irinotecan of 0.24 +/- 0.08. One objective response lasting 12 months in duration was observed in a patient with metastatic colon cancer. CONCLUSION: The recommended phase II dose of irinotecan of 10 mg/m(2)/d for 4 days weekly for 2 of 3 weeks was extremely well tolerated. Further efficacy testing of this pharmacologic strategy of administering intermittent low doses of irinotecan is warranted.

Adult↗
PubMed2000

Phase II trial of paclitaxel by 96-hour continuous infusion in combination with cisplatin for patients with advanced non-small cell lung cancer.

Our purpose was to determine the antitumor efficacy and safety profile of the combination of paclitaxel administered by 96-h continuous i.v. infusion followed by bolus cisplatin in patients with untreated advanced non-small cell lung cancer (NSCLC). Fifty-eight patients with untreated advanced or recurrent NSCLC were enrolled between October 1995 and December 1998. The median patient age was 60 years (age range, 34-75 years). Twenty-four patients were female. The majority of patients (n = 52) had an Eastern Cooperative Oncology Group performance status of 0/1. Twelve patients had stage IIIB NSCLC, 43 had stage IV disease, and 3 had recurrent disease after prior resection. Seven patients had received cranial irradiation for brain metastases, and 5 patients had received bone irradiation before enrollment. Patients were treated with paclitaxel (120 mg/m2/96 h) by continuous i.v. infusion followed by cisplatin (80 mg/m2) on day 5. Therapy was administered every 3 weeks as tolerated until disease progression or a maximum of six cycles. A total of 264 cycles of therapy were administered. Twenty-nine patients received all six cycles. Forty-six patients had measurable disease, with 20 patients achieving a partial response, and no complete responses were seen (overall response rate, 43%; 95% confidence interval, 29-60%). The median progression-free survival was 5.5 months. At a median potential follow-up of 27.2 months, the median survival for all 58 enrolled patients was 8.5 months, and the actuarial 1-year survival was 37% (95% confidence interval, 25.9-50.5%). This is the most extensive evaluation of prolonged continuous infusional paclitaxel in patients with advanced-stage cancer. In contrast to predictions from in vitro cytotoxicity models, the regimen does not appear to be obviously superior to shorter infusion times in the clinical setting. Additional trials of this regimen in patients with NSCLC are therefore of low priority.

Adult↗
PubMed1997

Diaschisis and neuropsychological performance after cerebellar stroke.

The cerebellum has been implicated in higher-order behavior. Blood flow studies (SPECT) have shown that cerebral diaschisis can appear after cerebellar lesions and this phenomenon could serve as a basis for a potential neuropsychological derangement after cerebellar insults. Our objectives in this study were to delineate the neuropsychological profile after cerebellar stroke, to evaluate cerebral diaschisis as measured by SPECT and to correlate the findings. We prospectively studied 26 patients with cerebellar stroke and 16 subjects matched for age, sex and educational level as a control group. A neuropsychological battery test, MRI and cerebral SPECT were performed in both groups. We found that cerebellar stroke results in motor control impairment and mild naming deficit, whereas no dysfunction in declarative memory, language, visuospatial or executive abilities is evident. The anatomical distribution of the lesion does not seem relevant in terms of neuropsychological impairment or diaschisis. Both ipsilateral and contralateral diaschisis as a result of a cerebellar stroke are found, but this phenomenon does not seem to result in overt neuropsychological derangement.

Adult↗
PubMed1994

[The gammagraphic diagnosis of acute pulmonary thromboembolism].

We aimed to determine the prevalence of acute pulmonary embolism (APE) in our population and to establish the diagnostic reliability of pulmonary scintigraphy (PS), as well as the influence of the clinical context (CC). During a 2-year prospective study, patients were diagnosed by either pulmonary angiography or normal-perfusion PS. A diagnosis of APE was made in 73 (75%) of a total of 97 patients. In the group of 58 patients diagnosed by ventilation/perfusion (V/Q) PS, 33 were classified as "highly probably" having APE; 32 of these in fact had the syndrome (sensitivity 88%, specificity 94%). Combining the "highly probable" patients with the "highly suspected" patients diagnosed by ventilation/perfusion PS, we obtained a sensitivity of 51% and specificity of 100%. Ventilation scintigrams were unobtainable in 28 older patients with greater dyspnea and tachypnea, who were unable to perform the maneuvers. Of the 21 "highly probable" patients as assessed by PS, 19 were diagnosed as having APE (sensitivity 86%, specificity 85%). Combining the "highly probable" patients with the "highly suspected" group, we obtained a sensitivity of 32% and specificity of 100%. Normal perfusion PS excludes clinically relevant APE. "Intermediate" or "slight" probability PS results, even when combined with CC, have no diagnostic validity.

Acute Disease↗
PubMed1994

Neuropsychological differences but comparable regional cerebral blood changes in asymptomatic HIV-1-positive and -negative drug addicts.

The objective of this study was to characterize the cognitive status of a population of asymptomatic HIV-positive drug addicts (patient group) to document the relationship between neuropsychological results and cerebral blood flow defects as measured by single photon emission computed tomography. As a control group we employed an age-matched population of HIV-seronegative drug addicts. Some neuropsychological differences were found between patients and controls and between drug addicts and normal population. We could not detect any difference in cerebral blood flow rates among HIV-1-positive and -negative drug addicts.

AIDS Dementia Complex↗