Photodynamic therapy for early oesophageal cancer.

BACKGROUND: Photodynamic therapy is an endoscopic treatment of early cancers based on the photosensitisation of neoplasms following the administration of a photosensitiser prior to laser light-induced tissue destruction. AIM: To assess the results of photodynamic therapy using Photofrin(Axcan Pharma Inc., Quebec, Canada) in patients with an early oesophageal cancer. PATIENTS: Twenty-four patients with early oesophageal cancer presenting as a not well-demarcated irregular dyschromic area of mucosa and unsuitable for any other treatment underwent photodynamic therapy. RESULTS.: Seventy-five per cent were successfully treated; three of them recurred and two died from head and neck cancer. To date, 54% of patients are alive without recurrence; the average follow-up is 21 months. There were one oesophageal lethal perforation and six stenosis. Results of photodynamic therapy were limited in this series by three failures, three recurrences and three deaths from previous head and neck cancers. CONCLUSION: This study provides some promising data for photodynamic therapy of oesophageal carcinomas in selected patients. It also emphasises the need for a best delivery device of laser light.

[Status of low-vision rehabilitation for age-related macular degeneration by orthoptists in the North of France]. / "Etat des lieux" en rééducation orthoptique Basse Vision dans la région Nord-Pas-de-Calais.

AIM OF THE STUDY: To evaluate the status of low-vision rehabilitation carried out by the orthoptists in the North of France. This study was a preliminary step in setting up a network between different vision professionals for the management of age-related macular degeneration (AMD) the North of France. METHODS: The ASO (Association Septentrionale d'Ophtalmologie) conducted a survey funded by the URCAM (Union Régionale des Caisses d'Assurance Maladie) with the FAQSV (fond d'aide à la qualité des soins de ville). The survey was based on the analysis of two forms sent to orthoptists of the North region of France. RESULTS: The survey analyzed 46 responses (a representative sample with 69% responses) providing a description of the orthoptists of the North of France: 19% males, 81% females whose mean professional experience was 13.3 years. Thirty-four percent of the orthoptists have had training in low-vision rehabilitation. This training was given during the university courses for 21% of responders and during a postgraduate course for 79%. Of the orthoptists surveyed, 64% worked in a private context, 9% in a public context, and 27% in both public and private contexts. Their main activity was in their own private practice for 60%, in an ophthalmologist's office for 20%, in a public institution for 16%, and a private institution for 4%. The mean number of patients treated was 70 per week per orthoptist, with 21% working mostly with children, 36% working mainly with adults between 16 and 60 years of age, and 7% with the elderly, whereas 36% reported no specificity related to patient age. The mean number of patients dealt with for low vision related to AMD was 4.1 per month per orthoptist. The average number of patients dealt with for low vision with no relation to AMD was 1.5 per month. The prescriber of low-vision rehabilitation was an ophthalmologist for 88.9% of the orthoptists and a general practitioner for 11.1%. Questions addressed to AMD patients: at the beginning of the survey, 83.8% of the patients did not have sufficient visual acuity to be able to read a text of current size (Parinaud 4); 40.4% of the patients required help for everyday life, and 59.6% were autonomous. For 7.1% of the patients, low-vision rehabilitation was carried out less than 1 month after the stabilization of retinal lesions, but in 35.3%, rehabilitation was carried out more than 2 years after lesions were stabilized. The main request of the patients involved improvement of near vision (89.9%). CONCLUSION: This survey will be a preliminary step in setting up a regional health network coordinating the ophthalmological and orthoptic management of AMD.

Quinine improves results of intensive chemotherapy (IC) in myelodysplastic syndromes (MDS) expressing P-glycoprotein (PGP). Updated results of a randomized study. Groupe Français des Myélodysplasies (GFM) and Groupe GOELAMS.

We designed a randomized trial of IC with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < or = 65 years with high risk MDS. Patients were randomized to receive Mitoxantrone 12 mg/m2/d d2-5 + AraC 1 g/m2/12 h d1-5, with (Q+) or without (Q-) quinine (30 mg/kg/day). 131 patients were included. PGP expression analysis was successfully made in 91 patients and 42 patients (46%) had positive PGP expression. In PGP positive cases, 13 of the 25 (52%) patients who received quinine achieved CR, as compared to 3 of the 17 (18%) patients treated with chemotherapy alone (p = 0.02). In PGP negative cases, the CR rate was 35% and 49%, respectively in patients who received quinine or chemotherapy alone (difference not significant). In the 42 PGP positive patients, median Kaplan-Meier (KM) survival was 13 months in patients allocated to the quinine group, and 8 months in patients treated with chemotherapy alone (p = 0.01). In PGP negative patients, median KM survival was 14 months in patients allocated to the quinine group, and 14 months in patients treated with chemotherapy alone. Side effects of quinine mainly included vertigo and tinnitus that generally disappeared with dose reduction. Mucositis was significantly more frequently observed in the quinine group. No life threatening cardiac toxicity was observed. In conclusion, results of this randomized study show that quinine increases the CR rate and survival in PGP positive MDS cases treated with IC. The fact that quinine had no effect on the response rate and survival of PGP negative MDS suggests a specific effect on PGP mediated drug resistance rather than, for instance, a simple effect on the metabolism of Mitoxantrone and/or AraC.

Non-invasive estimation of the circadian rhythm in serum cortisol in patients with ovarian or colorectal cancer.

The variability in toxicity or efficacy of cancer chronotherapy among patients may be due to differences in circadian rhythm. Adequate assessment of circadian rhythm often requires repeated blood sampling over at least a 24-hr period; this cannot be a routine procedure. We attempted to assess the reliability of a 2-timepoint estimate of the 24-hr rhythm of serum cortisol in 19 healthy subjects, 19 women with ovarian cancer and 18 patients with metastatic colorectal cancer. The difference between daily maximum and minimum values (MAX-MIN) was compared with that observed between values at 08.00 and at 16.00 (H8-H16). As significant correlations were found between both variables in all groups, we conclude that the magnitude of circadian changes in serum cortisol may be estimated from blood samples collected at 08.00 and at 16.00. The clinical relevance and the prognostic value of this method of assessment are currently under evaluation in a larger-scale clinical trial.

[Information for patients with cancer of the colon: results of a survey of gastroenterologists, surgeons, and oncologists of the North region]. / L'information des patients atteints d'un cancer du côlon: résultats d'une enquête réalisée auprès des gastroentérologues, chirurgiens et cancérologues de la région Nord.

This regional survey was aimed to detect hypothetical variations in attitudes among truth telling in colon cancer by an anonymous questionnaire sent to the 290 gastroenterologists, surgeons and oncologists of the Northern France area. The answers were assessed as always (A), often (O), rarely and never. Diagnosis was revealed to the patient (whether or not he asked the question) or to his spouse in 83%, 40% and 93% of the cases, respectively. The diagnosis of diffuse metastasis was revealed (A + O) to the patient or to his spouse in 23% and 95% of the cases, respectively. Only 3% of the physicians told (A + O) the patient that his condition was incurable while this aspect was A + O revealed to the patient's spouse in 34% of the cases. Most of the time, the diagnosis of colon cancer was revealed by oncologists rather than by surgeons or gastroenterologists. Conversely the full truth was more commonly told to the family by surgeons and gastroenterologists than by oncologists. We found variation in attitudes towards truth telling in colon cancer which depend on the physician's specialty. It seems to us that the magnitude of the full truth told to the patient or his family in Northern France area, is somewhat intermediate between the attitude of doctors in Northern Europe and in Latin Mediterranean or Eastern Europe countries.

What do gastroenterologists, surgeons and oncologists tell patients with colon cancer ? results of a survey from the northern france area

This regional survey was aimed to detect hypothetical variations in attitudes among truth telling in colon cancer by an anonymous questionnaire sent to the 290 gastroenterologists, surgeons and oncologists of the Northern France area. The answers were assessed as always (A), often (O), rarely and never. Diagnosis was revealed to the patient (whether or not he asked the question) or to his spouse in 83%, 40% and 93% of the cases, respectively. The diagnosis of diffuse metastasis was revealed (A + O) to the patient or to his spouse in 23% and 95% of the cases, respectively. Only 3% of the physicians told (A + O) the patient that his condition was incurable while this aspect was A + O revealed to the patient's spouse in 34% of the cases. Most of the time, the diagnosis of colon cancer was revealed by oncologists rather than by surgeons or gastroenterologists. Conversely the full truth was more commonly told to the family by surgeons and gastroenterologists than by oncologists. We found variation in attitudes towards truth telling in colon cancer which depend on the physician's speciality. It seems to us that the magnitude of the full truth told to the patient or his family in Northern France area, is somewhat intermediate between the attitude of doctors in Northern Europe and in Latin Mediterranean or Eastern Europe countries.

Short term response of circulating leptin to feeding and fasting in man: influence of circadian cycle.

OBJECTIVE: To investigate whether acute feeding induces changes in circulating leptin levels in humans and whether these changes vary according to nycthemeral cycle. METHODS: First experiment. Eighteen male subjects were given a fatty meal at 08.00 h. Blood sampling was performed for 10 h following this meal. Second experiment. Thirteen male subjects were given either a mixed meal or remained fasting either at night (starting at 01.00 h) or during the day (starting at 13.00 h). Blood samples were drawn every hour for a period of 8 h. RESULTS: First experiment. Serum leptin levels increased progressively from a mean (s.d.) baseline of 3.8 +/- 2.2 ng/ml to a value of 4.5 +/- 2.7 ng/ml (P < 0.01) 8 h after the fatty meal. Second experiment. During the day, serum leptin levels increased progressively from 2.65 +/- 1.7 to 3.34 +/- 2.2 ng/ml (P < 0.001) 6 h after the test-meal and decreased from 2.68 +/- 1.5 to 1.9 +/- 1.1 ng/ml (P < 0.001) 8 h after the beginning of the fasting experiment. Similar results were obtained at night. No statistically significant differences in leptin levels were observed between day and night sessions in response to feeding (mean area under the curve: 3.0 +/- 4.1 vs 4.1 +/- 4.1 ng/ml) and fasting (-2.9 +/- 2.2 vs -1.5 +/- 2.2 ng/ml). CONCLUSION: In two independent experiments, human serum leptin levels increase following food intake. This response is not influenced by nycthemeral cycle.

Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study.

Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < or = 65 years with high-risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m2/d days 2-5 + AraC 1 g/m2/12 h days 1-5, with (Q+) or without (Q-) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP-positive cases, 13/25 (52%) patients in the Q+ group achieved CR, compared to 3/17 (18%) patients in the Q- group (P = 0.02) and median Kaplan-Meier survival was 13 months in the Q+ group, and 8 months in the Q- group (P = 0.01). No life-threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP-positive MDS cases treated with intensive chemotherapy.

The time-pattern of rises and falls in proliferation fades with senescence of mortal lines and is perpetuated in immortal rat hepatoma Fao cell line.

Immortal cells perpetuate the rises and falls of proliferation that are progressively damped in mortal long-term cultured cells. For immortal rat hepatoma Fao cells, similar waves of proliferation occurred about every 3-4 wk. Under the same conditions, embryonic human fibroblasts and transformed but not immortalized embryonic fibroblasts display similarly recurring proliferation waves that progressively decrease in amplitude until senescence of the lines. In addition, strains of diploid normal human skin fibroblasts cultured under different culture conditions display a similar time-pattern of proliferation. Although the amplitude and baseline of these fluctuations are characteristic for each cell line, a common point was marked slow down in proliferation after every sequence of about 25 population doublings for all cells. Renewed proliferation waves of Fao cells allow about 22-23 additional population doublings each. Normal embryonic fibroblast culture and its transformed counterpart accumulate about 30 and 60 population doublings, respectively, before senescence. Normal fibroblast strains accumulate about 25 population doublings over their entire life spans. This halt in proliferation after every stretch of about 25 population doublings may correspond to a structural or functional stop following attrition of telomeric DNA. This putative stop may be bypassed once in transformed embryonic cells and repetitively in immortal cells. In support of this hypothesis, we observed rapid telomere shortening, in two steps, during divisions of mortal embryonic cells, and maintenance of long telomeres in immortal Fao cells, which may indicate episodic repair of telomeres. Alternatively, such maintenance of long telomeres may reflect survival and successive clonal growth of rare cells with long telomeres. We suggest that the balance between telomere attrition and repair processes regulates the waves of proliferation.

Pharmacologic modulation of reduced glutathione circadian rhythms with buthionine sulfoximine: relationship with cisplatin toxicity in mice.

The relationship between the rhythm in reduced glutathione (GSH) and that in cisplatin (CDDP) toxicity was investigated in a total of 560 male B6D2F1 mice, using buthionine sulfoximine (BSO). GSH was measured by high-performance liquid chromatography (HPLC) in four tissues, at each of six sampling times, 4 hr apart. A significant 24-hr rhythm was statistically validated in liver, jejunum, and colon, but not in bone marrow. Relative to liver, glutathione content was 56% in colon, 38% in bone marrow, 25% in jejunum, and negligible in kidney, where cysteine, a final product of GSH catabolism, displayed a 12-hr rhythmic variation. This rhythm may reflect that in the activity of GSH-degrading enzymes. BSO (450 mg/kg ip, 4 hr before sampling) reduced liver GSH threefold and kidney cysteine content was halved, but this pretreatment had no significant effect upon GSH content in the other organs. Furthermore, the period of the physiologic liver GSH rhythm changed from 24 hr to a composite (24 + 12 hr) period. This change in the period may result from an unmasking of the 12-hr rhythm in GSH-degrading enzyme activity by GSH synthesis blockade. Maximal values occurred in the mid-rest span and in the mid-active span after BSO administration. In the other tissues, the 24-hr period remained unchanged. BSO injection largely enhanced CDDP toxicity (as assessed by survival, leukopenia, and histologic lesions in kidney and bone marrow) and kidney mean platinum concentration. Furthermore, BSO pretreatment modified the period of CDDP toxicity rhythm: survival followed a significant 12-hr-rhythm, instead of a 24-hr rhythm. The cycling of GSH concentration results from a balance between synthesis and catabolism and likely constitutes one of the main components of the circadian rhythm in CDDP toxicity in mice.

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin.

A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Français des Myélodysplasies and European CMML Group.

We performed a randomized study of hydroxyurea (HY) versus VP16 in advanced chronic myelomonocytic leukemia (CMML) patients with CMML (according to French-American-British group criteria) and either documented visceral involvement (excluding liver and spleen infiltration) or at least 2 of the following: (1) neutrophils > 16 x 10(9)/I (2) Hemoglobin < 10 g/dL (3) platelets < 100 x 10(9)/L (4) marrow blasts > 5% (5) spleen > 5 cm below costal margin were eligible for this trial. Initial dosage was 1 g/d for HY and 150 mg/week for VP16, orally (doubled in case of visceral involvement). Doses were scheduled to be escalated up to HY 4 g/d and VP16 600 mg/week in the absence of response, and finally adjusted to maintain white blood cells (WBCs) between 5 and 10 x 10(9)/L. Crossing over was scheduled only in case of life threatening visceral involvement or major progression. The major endpoint of the study was survival. The study was closed on first interim analysis that showed a superiority of HY over VP16, after inclusion of 105 pts (HY arm: 53, VP16 arm: 52). Results of the second interim analysis, performed 7 months later, are presented here. Median age was 71 (range 38 to 91), median WBC count 20.10(9)/L (range 10 to 187). Thirteen pts had visceral involvement (3 serous effusions, 8 cutaneous infiltrations, 1 kidney, 1 bone infiltrations). Initial characteristics were similar in the HY and VP16 groups. Median follow up was 11 months in both groups (range 1 to 43+). Response to treatment was seen in 60% of the pts in the HY group, versus 36%, respectively, in the VP16 group (P = .02). Time to response was significantly shorter in the HY group (2.1 v 3.5 months, in the VP16 group, P = .003) and response duration was significantly longer in the HY group (median 24 v 9 months, in the VP16 group, P = .0004). The response rate of patients with visceral involvement was 3 out of 7 in the VP16 arm versus 5 out of 6 in the HY group. Three of the 10 pts crossed over from HY to VP16 responded as compared to 6 pts of the 11 pts crossed over from VP16 to HY. HY yielded better response on leukocytosis (P = .002). The effect on splenomegaly platelets, on hemoglobin level and transfusion requirement was similar in the 2 treatment groups. A significantly higher incidence of alopecia was noted in the VP16 arm (20% v 3%, P = .03). Fourteen (27%) and 20 (38%) patients in the HY and the VP16 group respectively, progressed to acute myeloid leukemia (difference NS). Twenty five (53%) and 44 (83%) patients in the HY and the VP16 group, respectively, had died (P = .002). Median actuarial survival was 20 months in the HY arm, versus 9 months in the VP16 arm (P < 10(-4)). Main factors associated with poor survival were allocation to the VP16 arm, "unfavorable" karyotype (ie, monosomy 7 or complex abnormalities) and anemia. In the HY group, unfavorable karyotype (P = .006), and low hemoglobin level (P = .004) were significantly associated with low response rates. Prognostic factors for poor survival in the HY group were also unfavorable karyotype (P = .001), and low hemoglobin level (P < 10(-4). In conclusion, we found that HY gave higher response rates and better survival than VP16 in advanced CMML. However, even with HY responses were only partial and survival was generally poor. This stresses the need for new agents in the treatment of CMML, that will have to be compared with HY in future randomized studies.

[Predictive value of the hemogram for myelotoxicity induced by the association of carboplatin-fluorouracil on the 4th day of the therapeutic regimen]. / Valeur prédictive de l'hémogramme du 4e jour pour la myélotoxicité induite par l'association carboplatine-5-fluorouracile.

The aim of this study was to determine the value of haematological counts at the 4th day of a chemotherapy cycle, in order to foresee neutro and/or thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed for 42 patients with locally advanced but non metastatic squamous cell carcinoma of head and neck, without prior chemotherapy. Lymphocyte counts were significantly decreased at the 4th day but normalized at the 8th day (P < 10(-6)). Decreases of lymphocyte and neutrophil counts at the 4th day were significantly correlated to grade > 2 neutropenia. The positive predictive value of lymphocyte or neutrophil counts is about 50% for some cut-off values but not high enough, with the schedule of chemotherapy in our study, to justify the systematic prophylactic therapy with haematopoietic growth factors.

[Unidimensionality of a functional measure for patient with an injured upper limb]. / Unidimensionnalité d'une mesure fonctionnelle pour des malades ayant une lésion du membre supérieur.

The construction of an instrument including a number of tests requires an analysis of its structure and its unidimensionality (which allows calculation of global score), and the determination of the difficulty level of various tests. This study examined a tool including 67 tests designed to evaluate the functional ability of patients with an injured upper limb. The patients seen in a rehabilitation centre during 12 months (173 subjects) were evaluated by the occupational therapists familiar with the tool. The statistical analyses were made using the principal component analysis method (PCAM), the Cronbach's coefficient and the Rasch model. The PCAM showed 3 principal factors which explained 44%, 10% and 4% of the total variance respectively in the case of patients with injured dominant limb. The predominance of the first axis and the high ratio of first by second eigenvalues suggested the unidimensionality of the tool. The Cronbach's value of 0.97 attested the good congruence of the items. The results obtained with the Rasch model seemed to be consistent with the hypothesis of the unidimensionality of the tool. This analysis also provided the difficulty scale of various tests. Similar results were obtained in patients with injured non dominant limb or with all the sample. The methods used provide complementary results.

Does induction chemotherapy with a mitoxantrone/vinorelbine regimen allow a breast-conservative treatment in patients with operable locoregional breast cancer? A French Northern Oncology Group trial in 105 patients. French Northern Oncology Group.

BACKGROUND: In recent years, induction chemotherapy has been tested by several investigators in the management of operable breast cancer. PATIENTS AND METHODS: Our current study was aimed to evaluate, pragmatically, in patients (74 stage II and 30 stage III) whose treatment would have been mastectomy, the percentage of them in whom a conservative treatment can be performed if primarily treated with a mitoxantrone/vinorelbine regimen. RESULTS: 67/104 patients (64%; 95% CI: 55-74%) had a conservative treatment (lumpectomy: 54, radiation therapy: 12, radiation therapy then lumpectomy: 1) Neutropenia was the major dose-limiting side effect, with grade 3 or 4 neutropenia registered in 83% of patients and 53.3% of the 442 cycles. Overall, a grade 3 or 4 non hematologic side effect occurred in 19.8% of patients and in 9.1% of cycles. One toxic death was observed after 2 cycles in a patient with aplasia who developped septicemia. Seventy one per cent of the patients experienced nausea and vomiting but grade 3 were observed in only 12% of the patients. Other side effects, including stomatitis, asthenia, alopecia, and constipation, were generally mild and uncommon. CONCLUSIONS: This mitoxantrone/vinorelbine regimen is an efficient induction treatment with only neutropenia as a noticeable side effect. It allows 64% of conservative treatment in patients whose treatment would have been mastectomy.

Granisetron (IV) compared with ondansetron (IV plus oral) in the prevention of nausea and vomiting induced by moderately-emetogenic chemotherapy. A cross-over study.

The French Northern Oncology Group carried out a randomised, cross-over study comparing two anti-emetic treatment strategies in 150 chemotherapy-naive patients, receiving their first two courses of moderately-emetogenic drugs. Nausea and vomiting were assessed using a self-administered questionnaire for five days. Anti-emetic treatments consisted of granisetron (G) 3 mg intravenously (iv) before chemotherapy or ondansetron (O) 8 mg intravenously, followed by 8 mg orally every eight hours for the next three days (for a total of 9 tablets). No significant difference was detected between treatment regimens in terms of their ability to control either acute vomiting (no vomiting - G = 72%; O = 77%) or acute nausea (no nausea - G = 54%; O = 47%), nor in terms of the number of total responders, (no emesis and no nausea) on day 1 (G = 52%; O = 45%) or on days 1- 5 ( mean G - 37%; O = 32%). Furthermore, there was also no significant difference between patient preference for the two treatments, either with regard to efficacy (G = 39%; O = 34%) or tolerability (G = 29%; O = 27%). In conclusion, no difference was observed between the two treatments.

[Contribution of computers to pharmacokinetics, Bayesian approach and population pharmacokinetics]. / Apport de l'informatique à la pharmacocinétique, approche bayesienne, pharmacocinétique de population.

A major objective for pharmacokineticians is to help practicians to define drug administration protocols. Protocols are generally designed for all the patients but inter individual variability would need monitoring for each patient. Computers are widely used to determine pharmacokinetic parameters and to try to individualize drug administration. Severals examples are summarily described: terminal half-life determination by regression; model fitting to experimental data; Bayesian statistics for individual dose adaptation; population pharmacokinetic methods for parameter evaluation. These methods do not replace the pharmacokinetician thought but could make possible drug administration taking into account individual characteristics.

Epilarynx: pharynx or larynx?

BACKGROUND: As a general rule, epilarynx is studied as a part of supraglottis. On the contrary, in France, due to its particular natural history, it is often studied separately. METHODS: To assess the value of this French classification, we compared from an epidemiologic point of view, in one study, 86 cases of epilarynx squamous cell carcinoma (SCC) with 431 oropharynx, 339 hypopharynx, and 89 vestibule SCC. In another study, we compared, from a clinical point of view, 232 epilarynx SCC with 1351 oropharynx, 652 hypopharynx, and 372 vestibule SCC. RESULTS: Epilarynx patients appeared to be much heavier drinkers than larynx patients and similar to pharynx patients but tobacco consumption did not differ. The patterns of nodal involvement were similar for pharynx and epilarynx SCC. For stages I and II, patterns of failures were similar, but for stages III and IV, there were fewer locoregional failures in vestibule patients; distant metastases were equally frequent for these tumors. From the standpoint of multiple primaries, epilarynx SCC appeared to be more akin to pharynx than to larynx SCC with a much lower incidence of lung cancers. Finally, the outcome after treatment was different for vestibule, epilarynx, and pharynx SCC, with a 5-year survival of 43%, 27%, and 13%, respectively. CONCLUSIONS: These data support the identification of epilarynx as a real entity that should be taken into account for stratification in clinical trials.

[Breast neoplasms: information in question(s). A survey of patients and physicians at a cancer treatment center]. / Cancer du sein: l'information en question(s). Enquête auprès des patientes et des médecins d'un Centre de lutte contre le cancer.

OBJECTIVE: The aim of this study was to know the wishes of our patients for information and to compare them with the point of view of our colleagues in a cancer center. METHODS: We gave 100 consecutive new patients with breast cancer a questionnaire about their needs. The same questionnaire was given in duplicate to all our colleagues in the cancer center (n = 53) asking: 1) their own needs of information if they had breast cancer 2) how they thought the patients would answer. RESULTS: Seventy-five percent of the patients and 81% of the doctors returned the questionnaire (28 were men and 15 women; 81% were involved in the management of breast cancer). On one hand, concerning information about the disease and about the treatment, there was no difference between the needs expressed by patients of doctors (as patients). As expected, the two groups wanted to be well informed. On the other hand, there was always a statistically significant difference between the needs expressed by patients and the opinion of doctors who systematically underestimated them. Concerning information to the family, 21% of doctors and only 4% of patients didn't want any information to be given to their family. Interestingly, 67% of the patients thought the decision had to be taken together with the doctor and 56% of the doctors (as patients) wished the decision to be taken by the doctor. CONCLUSION: Patients and physicians if they were patients, expressed the same high level need of information, but the patients needs seemed underestimated by the majority of doctors.