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A Lortholary

Publications and source records attributed to A Lortholary.

At least 19 recordsLinked to original sources
PubMed2004

Patient preference for either the EORTC QLQ-C30 or the FACIT Quality Of Life (QOL) measures: a study performed in patients suffering from carcinoma of an unknown primary site (CUP).

The objective of this study was to examine and compare two core measures of Quality Of Life (QOL) used in cancer clinical trials: the European Organisation for Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) and the Functional Assessment of Chronic Illness Therapy (FACIT), in order to identify which one patients have the strongest preference for using. 68 patients suffering from Carcinomas of an Unknown Primary site (CUP) were recruited in a multicentric study; all of them completed both questionnaires, administered in a randomised manner. The criteria were the percentage of preferences, and four indicators of acceptability. The results indicated that an equal proportion of patients preferred the QLQ-C30 (19%) and FACIT (19%). 54% of patients felt both questionnaires were acceptable. All the indicators of acceptability favoured the QLQ-C30. Analysis of open-ended questions shed light on the difficulties encountered by the patients. As no significant preference was observed for one of the questionnaires, the QLQ-C30 was chosen on the basis of its significantly better acceptability criteria.

Adult↗
PubMed2003

Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer.

The purpose of the study was to determine the efficacy and safety of docetaxel plus continuous infusion of 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracyclines. A total of 41 patients with histologically proven metastatic breast cancer and performance status 0-2, who had received at least one anthracycline-containing regimen, received docetaxel 85 mg m(-2) followed by continuous infusion of 5-FU 750 mg m(-2) day(-1) for 5 days every 3 weeks for up to eight cycles. All patients received corticosteroid premedication, but there was no prophylactic colony-stimulating factor support. The most frequent metastatic sites were the liver (61%), bone (29%), and lung (29%). All 41 patients were assessable for toxicity and 30 were eligible and assessable for efficacy. The objective response rate was 70.0% (95% CI: 53.6-86.4%) for the per protocol group and 53.7% (95% CI: 38.4-68.9%) for the intent-to-treat (ITT) population. For the ITT population, median duration of response was 8.4 months (95% CI: 6.7-12.2 months), median time to progression was 6.7 months (95% CI 5.5-8.6 months), and median survival was 17 months (95% CI: 12.3-not recorded months). Grade 3/4 neutropenia occurred in 54% of patients, with febrile neutropenia in 24% of patients and 5% of cycles, but infections were rare. Stomatitis was frequent, grade 3 in 24% of patients and grade 4 in one patient (2%), but manageable. Diarrhoea was rare, grade 3 in 7% of patients and 1% of cycles. Other grade 3/4 nonhaematological toxicities were infrequent. In conclusion, this docetaxel/5-FU regimen is highly active and well tolerated in patients with anthracycline-pretreated metastatic breast cancer. The efficacy is particularly promising, as one-third of patients were either second-line and/or anthracycline-resistant/refractory.

Adenocarcinoma↗
PubMed2001

Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.

PURPOSE: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM). PATIENTS AND METHODS: Patients with moderate to severe HCM (corrected serum calcium [CSC] > or = 3.00 mmol/L [12.0 mg/dL]) were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. A protocol-specified pooled analysis of the two parallel trials was performed. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. RESULTS: Two hundred eighty-seven patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. CONCLUSION: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.

Adult↗
PubMed2001

[Tumor-induced hypercalcemia. Review of bisphosphonate treatment].

INTRODUCTION: The incidence of tumor-induced hypercalcemia is between 10 to 20%. New treatments justify this review article. CURRENT KNOWLEDGE AND KEY POINTS: Tumor-induced hypercalcemia (half of all hypercalcemia) is divided into two groups: hematological tumors (10%), and solid tumors (90%), with osteolytic hypercalcemia and humoral hypercalcemia of malignancy (HHM: mediators include PTHrP). The two most common causes of tumor-induced hypercalcemia are lung cancer and breast cancer. Tumor-induced hypercalcemia most commonly disturbs gastrointestinal, neurological, renal and cardiovascular functions. These symptoms may be erroneously attributed to the underlying malignancy or its therapy. Prognosis of tumor-induced hypercalcemia is very poor, with median survival being about 3 months. Bisphosphonates have emerged as the standard treatment of tumor-induced hypercalcemia. The intravenous administration of isotonic saline is the first step in the management of tumor-induced hypercalcemia. Specific treatment of cancer remains essential to prevent TIH relapse. FUTURE PROSPECTS AND PROJECTS: New bisphosphonates have appeared, the most potent known bisphosphonate today is zoledronate.

Diagnosis, Differential↗
PubMed2001

[Cancers of unknown origin: 311 cases].

Carcinoma of unknown primary site has been defined as a metastatic disease without known primary site (upon clinical, radiological or endoscopic examination) at the initial therapeutic decision. The incidence of such carcinomas is between 1.6 and 15% of all adult's tumors. The goals of this retrospective and monocentric study were 1) the incidence of these carcinoma; 2) the utility to identify the primary site; 3) the efficacy of treatment in terms of survival; and 4) the prognostic factors to optimize strategic choices. Between January 1980 to December 1995, 311 cases were identified; this represents 1.6% of all cases treated in our center. Histological analyses of metastases revealed adenocarcinoma: 164 cases (92 males, 72 females; 29 well differentiated, 11 poorly differentiated and 41 undifferentiated); squamous cell carcinoma: 90 cases (78 males, 12 females); undifferentiated carcinoma: 27 cases (21 males, 6 females); neuro-endocrine tumor: 10 cases; and others: 20 cases. Median age was 61.1 years (30-94). Half of the patients had a PS between 0 and 1. The carcinoma was revealed by only one site of metastases in 35% of the cases (lymph node 72.9%, bone 35.5%, liver 19.4% and lung 16.5%). The primary carcinoma was found in only 6% of the cases. Median survival of all patients was only 9 months. Multivariate analyses by the Cox method show four positive prognostic factors: sex (female), performance status (PS < 2), histological analyses (squamous cell carcinoma), only one site of metastases.

Adenocarcinoma↗
PubMed2001

[PTHrP and breast cancer].

Parathyroid hormone-related peptide (PTHrP) has a high homology with the N-terminal portion of the parathyroid hormone (PTH). The gene of PTHrP is complex and can generate by alternative splicing at least three mature peptides containing 139, 141 and 173 amino acids. PTHrP acts via a common receptor with PTH but also via specific receptors. In physiological circumstances, PTHrP is produced locally in many normal tissues where it has autocrine/paracrine functions, particularly during embryonic development, growth regulation and differentiation of many cellular types. PTHrP has endocrine action on bone and kidney. The humoral hypercalcemia of malignancy is mainly mediated by PTHrP. Most hypercalcemic patients with solid tumors have increased plasma PTHrP, whereas PTHrP is not detectable in healthy subjects. During treatment with bisphosphonates, elevated plasma levels of PTHrP are associated with a weak response. PTHrP has also a significant role in the pathophysiology of bone metastases. PTHrP can induce a local osteolysis near the bone metastases, which favours their progression and thus participates in the autocrine regulation of tumor growth. In breast cancer, PTHrP is detected in about 60% of primary tumors and in more than 70% of bone metastases, whereas only 17% of nonbone metastases express PTHrP. A higher expression of PTHrP and its mRNA 1-139, is positively correlated with an invasive tumor phenotype and the development of bone metastases. PTHrP is an effector of transforming growth factor (TGFbeta) in the development and progression of osteolytic bone metastases. TGFbeta, which is released in bone matrix during osteolytic resorption, enhances tumor cells PTHrP production. Then, PTHrP stimulates bone resorption and develops tumor cells metastatic potential. Thus a feedback loop exists between carcinoma cells and the bone microenvironment, leading to a vicious circle.

Bone Neoplasms↗
PubMed2000

Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study.

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.

Adult↗
PubMed2000

[Case report forum: the example of French sarcoma group multidisciplinary discussion tools. Sarcomes de la FNCLCC].

Within the Rubis 4th framework of European project is led a pilot experiment of tools and services for health professionals in prospect for the Aquitanian healthcare network. The sarcoma group of the FNCLCC (47 people) uses on its web site a multidisciplinary dialogue with a specific discussion forum. This service allows the anonymous publication of a imaging clinical case and to start a take care discussion. 87 cases were published in 13 months involving 261 answers from February 1999 to February 2000. A case is published every 4 days on average and the deadlines for replies regularly drop (15 days in February 1999 down 1.1 day in February 2000). The cases are published either for a diagnosis or treatment request (30%) or for the physical preparation of meeting or for the continuous medical training (70%). There are many advantages in comparison with the other possibilities of discussion: availability, autonomy of publication, cost, number of experts participating. These NTIC services will be developing within the regional healthcare oncology networks and are already tested by other regional groups (Lymphoma) considering the simplicity of use, management and training of the functionality.

Community Networks↗
PubMed1999

Four years analysis of cancer genetic clinics activity in France from 1994 to 1997: a survey on 801 patients. French Cooperative Network/Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer.

AIM: In order to evaluate the characteristics and the evolution of cancer genetics activity in France, a survey was conducted at the national level during a period of 4 years from 1994 to 1997 through the French Cooperative Network, a multidisciplinary group formed to investigate inherited tumors. METHOD: A questionnaire was sent to all the 29 French non-specialized cancer genetic clinics to evaluate activity during a period of 4 consecutive weeks each year from 1994 to 1997. Items concerning the cancer genetic clinics, the consultees and the types of consultation were explored. RESULTS: A total number of 801 consultees were seen during the period of analysis. Some prominent characteristics of patients attending cancer genetic clinics were found. The majority of these are women (88%), and the mean age of consultees is 48 years. Fifty five percent of consultees are affected with cancer, and breast (personal and/or family history) is the most frequent site involved (63%). A genetic predisposition is certain or likely in about 53% of cases and unlikely in only 13% of consultations. The majority of consultations are devoted to new families (71%). The mean duration of consultations is 50 minutes, but 40% have a duration of at least 1 hour. Variations of several parameters during the 4 years period were observed and analyzed. Finally, since duration of consultations (more or equal to 1 hour) and personal or family history of breast/ovarian cancer appeared as pivotal elements in our study and consequently may affect the organization of clinics and the structuring as well as the evolution of cancer genetic activity in France, we analyzed more precisely the factors significantly associated with these 2 elements. CONCLUSION: Study compliance was fair (60% of centers) and these results give a good measure of cancer genetic activity in France. The variation of parameters from one year to another may reflect modifications in medical practice (medical orientation rather than research focus and content of cancer genetic clinics) and/or scientific breakthroughs in cancer genetics such as identification of genes predisposing to cancer.

Adult↗
PubMed1999

Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage.

PURPOSE: Patients with genetic fluorouracil (5-FU) catabolic deficiencies are at high risk for severe toxicity. To predict 5-FU catabolic deficiencies and toxic side effects, we conducted a prospective study of patients treated for advanced colorectal cancer by high-dose 5-FU. PATIENTS AND METHODS: Eighty-one patients were treated with weekly infusions of 5-FU and folinic acid. The initial 5-FU dose of 1,300 mg/m(2) was individually adjusted according to a dose-adjustment chart. Plasma concentrations of uracil (U) and its dihydrogenated metabolite, dihydrouracil (UH(2)), were measured before treatment, and the ratio of UH(2) to U was calculated. Pharmacokinetic and pharmacodynamic studies were conducted to look for a relationship between the ratio of UH(2) to U and 5-FU metabolic outcome and tolerance. RESULTS: The UH(2)-U ratios were normally distributed (mean value, 2.82; range, 0.35 to 7.13) and were highly correlated to (1) 5-FU plasma levels after the first course of treatment (r =.58), (2) 5-FU plasma clearance (r =.639), and (3) individual optimal therapeutic 5-FU dose (r =.65). Toxic side effects were observed only in patients with initial UH(2)-U ratios of less than 1.8. No adverse effects were noted in patients with UH(2)-U ratios of greater than 2.25. CONCLUSION: The UH(2)-U ratio, easily determined before treatment, could help to identify patients with metabolic deficiency and, therefore, a risk of toxicity.

Adult↗
PubMed1999

A dose-finding study of zoledronate in hypercalcemic cancer patients.

Zoledronate is a new heterocyclic imidazole bisphosphonate that is the most potent bisphosphonate administered in humans because it is 100-850 times more potent than pamidronate, according to in vitro or animal models of bone resorption. We conducted an open-label, dose-finding, single-dose phase I study in tumor-induced hypercalcemia (TIH), which has been similarly used as a model to determine the active doses of other bisphosphonates. The primary objective was to determine, with a dose escalation schedule, two nontoxic dose levels of zoledronate able to induce normocalcemia in at least 80% of patients with TIH after rehydration (corrected Ca for albumin levels >/=2.75 mmol/l). Based on estimates of potency, the starting dose was 0.002 mg/kg, and further tested doses were 0. 005, 0.01, 0.02, and 0.04 mg/kg. To obtain a more precise estimate of the response rate, we treated 10 more patients at the highest of the two effective dose levels. The median infusion time of zoledronate was 30 minutes. Thirty out of the 33 treated patients were evaluable for efficacy. Thirty percent of the patients had breast cancer and 54% had metastatic bone involvement. For all groups combined, mean Ca levels at baseline was 3.0 mmol/l. The two effective dose levels were 0.02 mg/kg and 0.04 mg/kg. Five out of five patients became normocalcemic after 0.02 mg of zoledronate/kg and 14 out of 15 after 0.04 mg of zoledronate/kg. The success rate of the latter dose was thus 93% (95% confidence interval [CI] 68-100%). At this dose, the first day of normocalcemia was day 2 or 3 for all but one patient. The duration of normocalcemia for the two effective doses could be assessed in nine patients; seven patients remained normocalcemic throughout the trial (32-39 days). The fall in serum Ca was accompanied by a marked fall in fasting urinary Ca excretion. Zoledronate was well tolerated: 7 out of 33 patients developed transient hypophosphatemia, and 3 developed transient hypocalcemia. The only clinically detectable side effect was an increase in body temperature occurring in 10 (30%) patients. In summary, very low doses of zoledronate (0.02 mg/kg and 0.04 mg/kg, i. e., 1.2 mg and 2.4 mg for a 60-kg individual, respectively) administered by a short-time infusion effectively treated patients with TIH. The fall in serum Ca was rapid, and normocalcemia was often maintained for several weeks. Zoledronate was well tolerated. Future trials will determine whether prolonged treatment with this potent compound can have greater effects on the skeletal morbidity rate in patients with tumor bone disease than can be achieved with currently available bisphosphonates.

Adult↗
PubMed1999

Systematic sequencing of the BRCA-1 coding region for germ-line mutation detection in 70 French high-risk families.

Seventy French high-risk families were screened for germ-line BRCA-1 mutations. The BRCA-1 coding region and the exon-intron boundaries were sequenced, except when pre-screening by PTT revealed a truncated protein in exon 11. Germ-line BRCA-1 mutations were detected in 24% of families. The number of breast and ovarian cancers per family, a relative young age at ovarian cancer diagnosis, and the occurrence of breast and ovarian cancer in the same patient significantly predicted the presence of a BRCA-1 mutation. The low BRCA-1 mutation frequency suggested that some alterations were not detected and some families were probably BRCA-2 or BRCAx carriers.

Adult↗
PubMed1999

[Mutation by deletion-insertion in BRCA-1 gene in three unrelated French breast/ovarian cancer families: possible implication of a mobile element].

A new type of mutation by deletion-insertion in BRCA-1 gene is found in three unrelated French breast/ovarian cancer families. Surprisingly, deletion and insertion occurred at the same nucleotide position at the end of exon 11 (3958del5ins4), thus generating a truncated protein. This original mutation consists in a deletion of 5 bp (CTCAG) and in an insertion of 4 different bp (AGGC). Here, we proposed two hypothesis to explain this phenomenom. The first hypothesis is the formation of a hairpin stem-loop structure comprising the mutational site and the sequence corresponding to the duplication insertion 2 nucleotides before the mutation. The second hypothesis, more speculative, consists in an abortive integration of a human mobile element as a human transposon (tigger 1) which involved a deletion of 5 bp during its excision and an insertion of 4 bases corresponding to the 5' extremity of the transposon.

Adult↗