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Biomedical subjects

E Guardiola

Publications and source records attributed to E Guardiola.

At least 19 recordsLinked to original sources
PubMed2004

Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer.

We report the results of a randomised phase II trial of docetaxel tested as a single agent in patients with recurrent head and neck cancer using methotrexate as a control arm to validate the results. Eligibility criteria included: histologically-confirmed squamous cell carcinoma, measurable disease, adequate haematological, renal and hepatic functions, no prior chemotherapy for recurrent cancer, signed informed consent. 40 mg/m2 methotrexate was given as a short weekly bolus i.v. injection, and 40 mg/m2 docetaxel was administered as a one hour weekly infusion. A total of 57 patients were randomised based on a ratio of 2/1:37 and 20 patients received docetaxel and methotrexate, respectively. Patient characteristics included 49 males and 8 females; the median age was 59 years (range: 43-82 years). Twenty-eight patients had a local-regional relapse and 29 had distant metastasis, the median disease-free interval was 7.9 months (range: 0-165 months). For patients treated with docetaxel, the following grade 3-4 toxicities occurred: neutropenia (12.5%) with febrile neutropenia in one patient (1%), anaemia (19%) mucositis (9%) and ungueal toxicity (9%). In the methotrexate arm, the grade 3-4 toxicities were: anaemia (15%) and mucositis (5%). The response rate was significantly higher in the docetaxel arm with 27% (95% confidence interval (CI): 21.7-32.3%) of objective responses versus 15% (95% CI: 11.2-18.8%) in the methotrexate arm. Overall survival and time to progression were super-imposable between the docetaxel and methotrexate treatments. Docetaxel given as a weekly infusion has a high activity in patients with head and neck cancer. A phase III trial is needed to test if this translates into a survival benefit for docetaxel use.

Adult↗
PubMed2003

[Epidermal growth factor receptors (EGFR): a new target for anticancer therapy].

Epidermal Growth Factor receptor (EGFR) are a key factor for the tumoral proliferation and its tumoral over expression appears to be a powerful prognosis factor. Currently, 2 types of treatments are targeting EGFR: a monoclonal antibodies anti-EGFR and a specific inhibitors of the EGFR tyrosine kinase. The administration of these compound alone or in combination with chemotherapy gives some promising results. These targets as anti-cancer therapy had emerged to be a new perspective for oncology.

Antibodies, Monoclonal↗
PubMed2003

Results of randomised phase II studies comparing S16020 with methotrexate in patients with recurrent head and neck cancer.

BACKGROUND: The purpose of this study was to carry out two randomised phase II trials of S16020, a new olivacine derivative, tested as a single agent in patients with recurrent head and neck cancer, using methotrexate as the control arm to validate the results. PATIENTS AND METHODS: S16020 at either 80 or 100 mg/m2 was administered as a 3-h infusion every 3 weeks. Methotrexate, 40 or 50 mg/m2, was given by bolus injection, weekly for a minimum of 6 weeks. In total, 36 patients were entered in the randomised studies (25 in an initial study, 11 in a confirmatory study) of whom 24 received S16020 and 12 received methotrexate. RESULTS: A scheduled interim analysis showed one patient having a non-confirmed objective response with S16020 and three patients having a confirmed objective response with methotrexate. In the methotrexate group, there were no patients with severe non-haematological toxicity. With S16020, there was a high incidence of severe non-haematological toxicities, including asthenia, oedema of the face, oedema and pain at the tumour sites and erythematous rash; consequently, both studies were stopped. CONCLUSIONS: Both studies were stopped due to the poor anticipated benefit/risk ratio for S16020, although time to progression and overall survival time were similar in both treatment arms.

Adult↗
PubMed2003

Pharmacokinetics of low-dose carboplatin and applicability of a method of calculation for estimating individual drug clearance.

BACKGROUND: Carboplatin is the only cancer drug for which conventional doses are individually adjusted according to estimated clearance and target area under the curve (AUC). The aim of this prospective study was (i) to evaluate intra- and interpatient variability of ultrafilterable (UF) carboplatin AUC(0-)(infinity) and (ii) to test whether the prediction of carboplatin clearance according to the Chatelut formula established for conventional carboplatin doses was accurate for low carboplatin doses. MATERIALS AND METHODS: Thirty-one head and neck cancer patients (29 men, two women, mean age 55.9 years) received concomitant radiotherapy (Rgamma 2 Gy/day) and chemotherapy (carboplatin 50 mg/m(2)/day i.v.) for 7 weeks: Rgamma was administered 5 days/week (days 1-5) and carboplatin 2 days/week (days 1 and 4). Pharmacokinetics was performed once per week. A limited sample strategy based on Bayesian analysis was first validated and blood was subsequently taken 1 and 4 h after the end of carboplatin administration. RESULTS: A total of 143 cycles was analyzed. Ultrafilterable carboplatin AUC(0-)(infinity) ranged from 0.360 to 4.200 mg.min/ml (mean 0.830, median 0.670). As a corollary, UF carboplatin clearance ranged from 19.1 to 244.7 ml/min. Ultrafilterable carboplatin concentrations were very stable over time: AUC(0-)(infinity) variability due to treatment duration contributed to <1% of the total variance, while interpatient variability contributed to 68.6%. Accordingly, intrasubject effect was not significant (P = 0.38) whereas intersubject effect was highly significant (P <0.001). These results suggest that optimal dosage for targeting a given AUC may vary within a 13-fold range between patients. The Chatelut formula, based on creatininemia, body weight, age and sex, over estimates carboplatin clearance by 40% on average (bias 95% CI 29.6% to 51.1%). No significant relationship was observed between either bone marrow toxicity or creatinine clearance decrease and carboplatin pharmacokinetics. CONCLUSIONS: The Chatelut carboplatin clearance model established for conventional carboplatin dosages (>100 mg/m(2)) is not applicable for targeting low AUC (<1 mg x min/ml).

Adult↗
PubMed2003

Phase I and pharmacokinetic study of the association of capecitabine-cisplatin in head and neck cancer patients.

The combination of cisplatin and 5-fluorouracil (5-FU) is considered to be the standard treatment in induction chemotherapy for patients with squamous cell carcinoma of the head and neck. Capecitabine (Xeloda) is an oral fluoropyrimidine that is preferentially activated at the tumoral level, exploiting the higher thymidine phosphorylase activity in tumoral tissue. This phase I trial was conducted in patients with locally recurrent or metastatic head and neck carcinoma. The treatment plan included cisplatin on day 1 every 21 days, followed by capecitabine twice daily from day 2 to day 15, with a 1-week rest period. Pharmacokinetic investigations concerned plasma measurement of unchanged capecitabine, 5'-deoxy-5-fluorocytidine, 5'-doxifluridine and 5-FU using an optimized high performance liquid chromatography method, and cisplatin measurement in plasma using a limited sampling procedure. Twenty-one patients were included (mean age 61 years, range 46-76 years). Dose (mg/m(2)) increments for cisplatin and capecitabine (b.i.d.), respectively, were as follows: level 1, 80 and 1000 (three patients); level 2, 100 and 1000 (12 patients); and level 3, 100 and 1125 (five patients). Dose-limiting toxicities occurring during the first cycle (grade >/= 3) were observed on level 2 (one patient with diarrhea, nausea, vomiting, hand-foot syndrome, one toxic death due to renal failure and neutropenia, one patient with neutropenia) and on level 3 (one patient with diarrhea, one patient with hand-foot syndrome and one patient with neutrothrombocytopenia). Due to delayed side-effects, 14 patients (67%) had repeated cycles every 28 days instead of 21 days as initially planned. Objective response was obtained in seven patients (three complete responses and four partial responses). There was no evidence of pharmacokinetic-pharmacodynamic relationships with the drugs and metabolites investigated. Combination of capecitabine and cisplatin is feasible, with a very promising response rate. The recommended doses for further phase II studies are those of level 2 with cisplatin 100 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) b.i.d. on days 1-14, every 28 days.

Administration, Oral↗
PubMed2001

Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and neck cancer patients: A long-term quality of life analysis.

BACKGROUND: The purpose of this study is to make a comparative analysis between acute toxicity with late toxicity. This study is based upon a French quality of life (QoL) questionnaire in a cohort of advanced head and neck (H&N) cancer patients treated by concomitant twice-a-day continuous radiotherapy with no acceleration and chemotherapy with cisplatin and 5-fluorouracil. METHODS: From September 1992 to November 1997, a prospective data bank of 91 patients was constituted. In November 1999, 31 patients were still alive and followed for more than 3 years. All patients had stage IV strictly unresectable squamous cell carcinoma of oropharynx or hypopharynx. A French specific H&N cancer QoL questionnaire was used at the end of radiotherapy and at the last date of follow-up of each patient (during 1999). p values reflect comparison of percentages obtained at the end of treatment with percentages at long-term follow-up. Statistical analysis was performed using chi(2) test (p <.05 considered as significant). Percentages obtained by the QoL questionnaire correspond to moderate-severe problems only. RESULTS: Twenty-nine of 31 (94%) patients participated in the QoL study. Acute treatment toxicities were severe with declines in virtually all QoL and functional domains. Globally, with an average long-term follow-up of 4.5 years (range 3-7 years after treatment), there is a statistical improvement in the following symptoms: dry mouth and sticky saliva (97% versus 55%, p <.05); tasting problems (35% versus 21%, not significant); swallowing problems (77% versus 36%, p <.05); and H&N pain (86% versus 9%, p <.05). Financial problems were not improved (21% versus 14%, not significant), and psychological problems (59% versus 5%) were statistically significant. Fourteen of 29 (48%) patients were drinking and 8 of 29 (28%) were smoking at long-term follow-up; at the diagnosis they were 86% and 90%, respectively. At long-term follow-up 22 of 29 presented good or very good QoL, and 25 of 29 said they had improved their initial QoL. CONCLUSION: The interest of twice-a-day radiotherapy with concomitant chemotherapy is to increase total radiotherapy equivalent dose without increasing late toxicity and also to improve locoregional control, survival, and long-term QoL/effectiveness ratio. Best supportive care is recommended to obtain both good QoL and cancer control in a long-term follow-up.

Adult↗
PubMed2001

The relationship of epidermal growth factor receptor levels to the prognosis of unresectable pharyngeal cancer patients treated by chemo-radiotherapy.

The aim of this study was to analyse prognostic factors for time to treatment failure (TTF) and overall survival (OS) in patients with unresectable cancer of the pharynx. A twice daily (b.i.d.) radiotherapy with concomitant cisplatin-5-fluorouracil chemotherapy was administered to 77 consecutive patients (68 males, 9 females; median age: 56 years). The studied factors were: age, gender, tumour differentiation, tumour volume, initial hemoglobin level, karnofsky index (KI), primary tumour location, T, N, epidermal growth factor receptor (EGFR) level in the tumour (fmol/mg protein). KI and EGFR level were significant predictors in a multivariate analysis for TTF (P=0.004 and P=0.0001) and OS (P=0.004 and P=0.0001). In order to select subgroups with different outcomes, a stratification of patients was performed based on the EGFR value: patients with tumour EGFR levels <35 fmol/mg protein, between 35 and 275 fmol/mg protein and >275 fmol/mg protein had 95%, 51% and 16% 3 year OS rates, respectively (log rank test; P=0.0001). Interestingly, for patients exhibiting a complete response (CR) after concomitant b.i.d. chemo-radiotherapy, patients with EGFR levels <35 fmol/mg protein were all alive at 3 years; in contrast, there was only 70 and 13% 3 year survival rates for patients with EGFR tumour levels between 35 and 275 fmol/mg protein and above 275 fmol/mg protein, respectively. EGFR determination appears to be a powerful prognostic parameter in unresectable pharyngeal cancer patients treated by concomitant chemo-radiotherapy.

Adult↗
PubMed2001

Combination of cisplatin-doxorubicin-cyclophosphamide in adenocarcinoma of unknown primary site: a phase II trial.

The purpose of this report is to evaluate toxicity, response, and survival of the cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy regimen in patients with adenocarcinoma of unknown primary site (ACUP). Twenty-two patients with ACUP were eligible for this study between June 1992 and April 1999. There were 13 men (59%) and 9 women (41%) with a median age of 53.5 years (range: 29--78 years). Lung (seven), liver (six), vertebral bone site (six), and abdominal nodes (six) were the most common metastatic sites. Treatment consisted of doxorubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and cisplatin 100 mg/m(2) (CAP), administered every 3 weeks; a total of six courses were planned. Twenty-two patients were assessable for toxicity and 20 patients were assessable for response. Grade III to IV neutropenia was observed in 14 patients (64%); febrile neutropenia occurred in 6 patients (27%) and in 10 cycles (12.5%). Grade III to IV anemia and thrombocytopenia were found in 12 (54.5%) and 9 patients (41%), respectively. Grade III to IV nausea and vomiting was observed in 9 patients (41%). Ten patients, 50% of the assessable population, obtained an objective response, including 3 complete (15%) and 7 partial (35%) responses. The median response duration was 3.9 months (range: 0.5--13.3 months). One patient (5%) had stable disease and 5 patients (25%) had progressive disease. The median overall survival and the median time to progression were 10.7 months (range: 0.4--56.9 months) and 8.8 months (range: 6.6--16.5 months), respectively. The CAP regimen in patients with ACUP had significant activity. This chemotherapy regimen induced a high level of grade III to IV toxicities and could not be considered as a treatment of reference. However, the emergence of long-term survivors among responder patients highlighted the need to search for an active treatment for patients with ACUP.

Adenocarcinoma↗
PubMed2001

An analysis of articles on neonatal pain published from 1965 to 1999.

OBJECTIVE: To analyze articles on neonatal pain indexed in MEDLINE from 1965 to 1999. METHODS: Papers published since 1965 and indexed in Medline (PubMed ) were considered. The search strategy was: 'pain' (MeSH terms) OR 'pain' (Title word) OR 'pain' (All Fields), AND 'infant, newborn' (MeSH terms). After the search was completed, a printed copy of the references was obtained, and each reference was reviewed to establish its pertinence to the study's objective. For each article, the year of publication, the journal of publication, the language of the journal, the country of the first author, the type of article and the subject were analyzed. RESULTS: Only 545 of 2490 references identified by the MEDLINE search were considered to deal with neonatal pain. Few articles on neonatal pain were published from 1965 to 1985, but the number of articles published on this topic increased sharply after 1985. Most of the papers were published in English (84.6%). The United States, Canada and the United Kingdom were the main countries that published neonatal pain articles (38.6%, 14.2% and 13.3%, respectively). Clinical research articles (31.7%) were published most frequently; the main subjects of all the articles were pain related to colic (20.4%), general neonatal pain issues (13.6%) and procedural pain (13.4%). Pediatrics and Archives of Diseases in Childhood were the journals that published the most articles on neonatal pain (27 and 22, respectively). CONCLUSIONS: Pain in neonates was a neglected subject of publication until the mid-1980s, and, currently, only a few countries seem interested in this type of pain. This lack of interest may be related to the undertreatment of pain in the neonatal period.

Demography↗
PubMed2001

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck.

OBJECTIVE: Twenty-seven patients with recurrent squamous cell carcinoma of the head and neck were entered in a multicenter study to determine the efficacy of the paclitaxel-carboplatin association. METHODS: Standard eligibility criteria applied, i.e. measurable disease, and chemotherapy given as induction treatment or concomitant chemoradiotherapy was allowed if completed more than 6 months prior to the study. Every 21 days, paclitaxel 175 mg/m(2) and carboplatin AUC 6 were administered. The patient group included 3 females and 24 males with a median age of 61 years (range 39-75 years). RESULTS: All patients were assessable for toxicity and 24 for responses. Main grade 3-4 toxicities were: neutropenia (62.9%), febrile neutropenia (18.5%), anemia (11.1%), thrombocytopenia (14.8%), mucositis (7.4%) and vomiting (7.4%). Among the intent-to-treat population, 29.6% of patients had an objective response, with a median response duration of 4.2 months (range 1-5.7 months). Stable and progressive disease were observed in 11.1 and 48.1% of patients, respectively. The median overall survival was 7.2 months (range 0.5-10.9 months). CONCLUSION: From these data, paclitaxel-carboplatin seems to have an activity in recurrent squamous cell carcinoma of the head and neck, but the high level of toxicity highlights the need to search for a safer chemotherapy combination.

Adult↗
PubMed2001

Clinical prognostic factors for patients with recurrent head and neck cancer: implications for randomized trials.

The purpose of our study was to determine the clinical prognostic factors for the duration of the overall survival from recurrence (OSR) in patients with recurrent head and neck squamous-cell carcinoma. We performed a retrospective analysis on 496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The significant favorable prognostic factors for the OSR were: initial T(1-2) (p = 0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of disease-free interval (DFI; p = 0.0001), performance status (PS) 0-1 (p = 0.004) and local-regional recurrence (p = 0.001). In the multivariate analysis, the apparent nonsignificance of all factors apart from the DFI suggested that relevant prognostic factors could be embedded in the DFI. Multivariate analysis was performed after excluding the DFI. The results indicated that local-regional recurrence, PS 0-1 and no initial chemotherapy exposure remained significant favorable prognostic factors for the OSR. The advantages of taking into account such prognostic factors are to eliminate the patient selection bias and to ensure a fairer comparative evaluation of new or already existing agents in recurrent head and neck cancer.

Adult↗
PubMed2000

An analysis of potential factors allowing an individual prediction of cisplatin-induced anaemia.

Severe cisplatin (CP)-induced anaemia significantly impairs the patient's quality of life. Prevention based on erythropoietin (EPO) administration would be cost-effective providing that individual predictive factors of anaemia are identified. The aim of the present study was to identify parameters able to predict the occurrence of CP-related anaemia. This prospective study was conducted on 40 head and neck cancer patients receiving a CP (100 mg/m(2), intravenous (i. v.) on day 1) - 5-fluorouracil (5-FU, 1 g/m(2)/dx5 days by continuous infusion) induction chemotherapy. Three cycles were given at 3-weekly intervals. Platinum pharmacokinetics (total and ultrafilterable plasma platinum concentration measured 16 h after CP administration) and 5-FU pharmacokinetics (full-cycle plasma area under the curve, (AUC(0-105h)30 g/l) occurred in 15 patients (38%) and 3 of them also received a blood transfusion. Patient age, 5-FU AUC(0-105h) and total platinum concentration were unrelated to Hb loss. In contrast, ultrafilterable (UF) platinum concentration was significantly correlated to Hb loss: the higher the UF platinum concentration, the greater the Hb loss (P=0.015). A discriminant analysis allowed a cut-off value for UF platinum to be proposed to identify patients developing significant loss of Hb: 91% of patients exhibiting a UF platinum concentration above 50 ng/ml developed significant loss of Hb in contrast to 18% in the group of patients with a UF platinum concentration below 50 ng/ml (odds ratio (95% confidence interval, CI) of 46 (4.7-446)). In conclusion, the present platinum pharmacokinetic survey may be proposed as a valuable approach to identify patients at risk for developing severe anaemia.

Adult↗
PubMed1998

[Books on anesthesiology and resuscitation published in Spain. An approach to their study].

INTRODUCTION: Few authors have examined the publication of medical books. Our aim was to analyze the nature of books published in Spain on anesthesiology and recovery. MATERIAL AND METHODS: Books listed by the Spanish ISBN agency were selected if they included anestesi* or reanima* in any field. Duplicates were removed. Multiple editions or references were considered single books, with data for the oldest edition entered into analysis. Multiple volume collections were grouped as complete works. Data analyzed for each book were year of publication, language (of publication and the original), subject (according to ISBN classification) and place of publication. Nine subject classifications were applied: general, recovery, anesthetic techniques, pharmacology, obstetrics/gynecology, pediatrics, veterinary anesthesia, dental anesthesia and miscellaneous. RESULTS: We analyzed 216 books. Years that saw publication of the greatest number of books were 1988 (17), 1993 (16) and 1979 (15), and the five-year period in which the most books were published was 1985 to 1989 (48 books, 22.2%). Most books (114, 52.8%) were originally written in English, Spanish being the second most common original language (58, 26.8%). All books were published in Spanish. The Spanish ISBN classification system identified 11 categories: general diseases/clinical medicine/therapy (161, 74.5%); drugs/pharmacology/physical therapy/toxicology (20, 9.3%); gynecology/obstetrics (9, 4.2%), veterinary medicine (9, 4.2%) and medicine (8, 3.7%). Classification by specific subjects showed a predominance of monographs or treatises on general aspects (42, 19.4%) followed by books on recovery (37, 17.1%), anesthetic techniques (25, 11.6%) and pharmacology (17, 7.9%). Most books were published in Barcelona (142, 65.7%), Madrid (36, 16.7%) or Saragossa (10, 4.6%). CONCLUSIONS: Spanish publication of books on anesthesiology and recovery has increased in recent years. Most books are translations usually from English. Spanish ISBN agency data, although it has limitations, can be useful for locating books published in Spain on anesthesiology and recovery. It would be useful to introduce keywords into the ISBN data base so that books on specific subjects could be classified and retrieved.

Anesthesiology↗
PubMed1996

[Books published in Spain on smoking].

Tobacco dependence, considered for a long time as a habit and, more recently, as an addiction, has many bad effects in health. The objective of this study was to analyse books published in this field in Spain. Books indexed in the ISBN Spanish database in CD-ROM (updated to 1993) dealing with addiction to tobacco, that included one of the following words: tabac*, tabak*, tabaq*, fuma*, fumad*, nicotine*, alquitran*, antitabac*, antitabaq*, cigarro*, cigarri*, exfumad*, pipa*, puro*, picadura* or filtro, were included in the study. Authors, ISBN classification, year of publication, language (of publication and original) and publishers were descriptively analysed. One hundred and four books were analysed. The highest number was published during the period 1990-1993 (42%); being 1993 (n = 15) and 1991 (n = 14) the most productive years. A big increase was observed from 1985. A great number (76% of books, n = 79) was written by personal authors and the 14% (n = 14) by public organizations. Most of the books (n = 88; 85%); were published in Spanish, followed by Catalan (n = 13; 13%); 21 books (20%) were translations: most of them from English (n = 12; 60%) or from French (n = 3; 14%). Forty six per cent of books was published by trade publishers and 31% by public organizations. According to the ISBN classification, these books were grouped in 20 different topics; but, most of them (70%) were included in three of these topics: hygiene (n = 42, 40%), pharmacology-toxicology-drugs (n = 18, 17%) and pathology-diseases and medical/therapeutical clinical practice (n = 14; 13%). The number of books published in Spain dealing with tobacco dependence has increased very much from 1985; it suggests that interest in this area in SPain has also increased. Most of the books are published in Spanish, and the most frequently translated language is English. These books are basically published by trade publishers and public organizations. These results have to be considered taking into account that fighting against consumption of tobacco and tobacco dependence is a relatively new area of research and study.

Bibliographies as Topic↗
PubMed1995

[Published books on pain and its treatment in Spain. Analysis with the ISBN database].

INTRODUCTION: Although analyses have been done on the publishing of scientific articles on pain in Spanish, book publications in the field have not been studied. This article fills that gap. MATERIAL AND METHODS: A bibliography of books with pain approached from a medical standpoint was compiled from ISBN CD-ROM database (updated for 1993). Books going into more than one edition were considered single titles. Multi-volume collections were considered single books. We analyzed type of book, subject, ISBN classification, year, language (of publication and original), publisher and place of publication. RESULTS: Two hundred books were studied. Over 60% had been published within the previous 10 years. The year that showed the most books published was 1990 (19) followed by 1989 (16) and 1988 (16). Output has been rising steadily. One hundred ninety-eight books were published in Spanish and 2 in Catalan. The original language was Spanish in 114 cases, English in 51 cases, French in 21 and German in 7. By ISBN classification, most (146) covered pathology, disease and medical/therapeutic clinical practice. By topic, 51 books were general, 41 treated lumbalgia, sciatica or back pain and 35 covered headaches in general or migraine. Most of the books were issued by trade publishers. The cities most often involved were Barcelona and Madrid. CONCLUSIONS: An increased number of books about pain are being published in Spain, coinciding with a rise in the publication of scientific articles on the subject.

Databases, Bibliographic↗