[Nutritional workshops for cancer patients: a pilot approach]. / Les ateliers de nutrition en oncologie médicale: une expérience pilote.

The authors describe an original experience with 3 years of a nutritional workshop for cancer patients. This intervention combine an information about nutritional aspects of cancer with psychosocial support, to buffer psychological and nutritional consequences of cancer. The workshop, leaded by two specialized teams, one in medical oncology, the other in public health, is proposed to patients during and after a specific treatment. In one day, it provided information about nutrition and cancer, diet education and psychosocial support with supportive-expressive group. At this day, the evaluation of this intervention is only subjective. Fifty-six patients participated in at least one workshop, with majority of women (91%). Nineteen workshops were leaded with average participant number of 7 per workshop the third year. The authors believe that nutritional workshops are of great help for cancer patients, by enhancing social reinsertion, giving opportunity of emotional expression and humanizing the treatment. Our experience show it is possible to propose psychosocial intervention in institution in the context of Mediterranean country. We are leading currently a study that will permit a more systematic evaluation of the effects of this intervention.

[Clinical pilot study on repeated use of heparin, vancomycin, colimycine locked flush solution for central intravenous implanted catheter in oncology]. / Etude clinique pilote de l'utilisation repétée dune solution héparine, vancomycine, colimycine en verrouillage systématique des chambres implantables avec cathéter centeral en cancérologie.

With an anti-infectious and an antithrombotic prophylaxis aims, a locked flush solution including heparin and vancomycin, was used systematically for implantable venous access system for each patient, from january to april 1995. Since the 6th of april 1995, in order to widen the antibiotic spectrum on Gram negative bacteriae, we added colimycin at the flush solution. In 1995, 342 hospitalised patients held this type of venous access and received chemotherapy and/or radiochemotherapy for cancer. Two thousand six hundred thirty three manipulations were done, 575 with the first flush solution, 2058 with the second. During the year, 15 implantable access system (4.4%) were considered as infected, only 3 (0.9%) were removed, in the first period. THe infectious rate seemed to be stable, but the bacterial assessment to be modified between the two periods. The Gram negative bacterial infections seemed to decrease with colimycin addition (33% versus 50%). These results must be confirmed by a long term and/or randomized study.

A Bayesian dosing method for carboplatin given by continuous infusion for 120 h.

Carboplatin (CBDCA), an analogue of cisplatin, exhibits reduced toxicity but wide interpatient variability of its pharmacokinetic parameters. Individualization of the CBDCA dose is therefore necessary. Although various formulas have been developed for this purpose, major side effects have been reported on CBDCA administration by short-term infusion (0.5 or 1 h). We therefore propose a new schedule of CBDCA administration. Instead of a dosing method based on the estimation of renal function when a classic administration schedule is used, we propose a pharmacokinetic dosing method (Bayesian method), whereby CBDCA is given by continuous infusion for 120 h. First, CBDCA was given to 21 patients to determine the population pharmacokinetic parameters of carboplatin. Then, on the basis of total platinum plasma concentration measurements and Bayesian estimation of pharmacokinetic parameters, it was possible to individualize the CBDCA dose within the first 24 h of the infusion. This new protocol for CBDCA administration was evaluated in 36 new patients (60 courses). Three theoretical end points at the end of the infusion were considered. For a given theoretical end point, 20 courses were taken into account. The theoretical end points (i.e., 1, 1.5, and 1.8 mg/l) were compared with the concentrations measured at the end of the infusion, which were 0.99 +/- 0.10, 1.41 +/- 0.13, and 1.72 +/- 0.20 mg/l, respectively. This Bayesian dosing method can easily be used in clinical practice, and the determination of predictive performances has shown that the method is precise and unbiased. With no more toxicity or practical difficulties than those produced by other methods, and with acceptable tolerance, it was possible to reach a median dose that was 20% higher than the usual dose (484 +/- 190 mg/m2 as compared with 400 mg/m2). In conclusion, this new schedule of CBDCA administration appears to be interesting in terms of tolerance. However, new studies are required to confirm that this new scheme leads to equal or better efficacy than the classic protocol.

[Individual dose adjustment of high-dose methotrexate in clinical practice]. / Adaptation individuelle de posologie du méthotrexate à haute dose (MTX-HD) en pratique clinique courante.

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, the concept of high-dose methotrexate has been proposed. The use of rescue by folinic acid, as well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted us to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. Individual adaptation of posology, calculated using the test dose or according to population pharmacokinetic with a Bayesian method of parameter estimation (which allows us to adjust the dose of high-dose methotrexate during its infusion) permits control of inter and intra-individual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by high-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogeneous group of patients). Theoretical maximum concentration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum security for the patient with no serious side effects (no grade 4 toxicity according to WHO classification), while receiving an optimum dose of methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on average 65% more than the usual dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).

Immunomodulation by NPT 15392 in cancer patients under chemotherapy.

A clinical trial of NPT 15392, a purine derivative, was run in ten head and neck cancer patients presenting signs of immunosuppression and undergoing repeated chemotherapy. A battery of ten tests was used to assess the immune status of the subjects. Those tests included skin tests, lymphocyte investigations (count, E-rosetting, membrane fluorescence and lymphoblastic transformation) and determination of serum levels of C'3 fraction of complement and IgA. The drug induced transitory, immune stimulation during or after treatment without any side effects. NPT 15392 seemed to selectively exert an action on T lymphocytes. Inasmuch as transitory, immune stimulation and secondary immune depression were noted after treatment, the therapeutic protocol for use of this drug should be reexamined.

[Incidence, prognosis and prevention of septicaemias in patients under treatment for acute leukaemia (author's transl)]. / Incidence, pronostic et prévention des septicémies chez les malades traités pour leucémies aiguës.

Septicaemias are frequent and severe in patients with acute leukaemia under aplastic treatment. The present study concerns 69 such patients: 29 with acute lymphoblastic leukaemia (ALL), and 40 with acute non-lymphoblastic leukaemia (ANLL). All were treated in single rooms in the same hospital and in similar conditions. The overall incidence of septicaemia was 62%; it was 60% in patients with recently diagnosed ALL and 68% during relapses. More than 34% of ALL patients and 82.5% of ANLL patients had one or several episodes of septicaemia. Among the 74 pathogens isolated 50% were Gram-positive organisms, 45% Gram-negative organisms and 5% Candida spp.. The first episodes of septicaemias were predominantly caused by Gram-positive spp. (61%) and the subsequent ones by Gram-negative spp. (60%). The primary infection could only be diagnosed in 19% of the cases and was most frequently located in the digestive tract or perineal region. The most common focal complications were lung infections (18 cases), skin infections (12 cases) and septic shock (15 cases). Seventy-four p. cent of the patients survived with prompt and potent antibiotic therapy. Death occurred in 26% and was clearly related to the following factors: chemotherapy of relapsed leukaemia and/or blastic aplasia and/or successive episodes of septicaemia. The incidence and severity of septicaemias in leukaemic patients will only be reduced by improved prophylactic measures against infection and by less pronounced and shorter chemotherapy-induced granulocytopenia.

Maintenance chemoimmunotherapy of nonlymphoblastic acute leukemias.

A trial of maintenance chemotherapy of nonlymphoblastic acute leukemia led to a comparison of two groups of patients in complete remission. Group 1 (14 patients) received only monthly reinduction chemotherapy. Group 2 (17 patients) received identical chemotherapy together with weekly immunotherapy combining BCG and irradiated leukemic cells. While the duration of the first complete remission was unmodified, the overall survival time and, above all, survival after the first relapse were prolonged in group 2 chemoimmunotherapy. These results were all the more marked when a homogeneous group of patients having received the same induction chemotherapy were considered.

High-dose methotrexate: a clinical and pharmacokinetic evaluation. Treatment of advanced squamous cell carcinoma of the head and neck using a prospective mathematical model and pharmacokinetic surveillance.

Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in the frequency and severity of toxicity. The onset of clinical toxic manifestations was significantly correlated with a poor therapeutic response and poor prognosis. The patients were classified in to three groups according to poor, intermediate, and good pharmacokinetic parameters calculated after an intravenous identification dose of methotrexate. These group allocations had a very high prognostic value with regard to toxicity, and especially to the quality of therapeutic response to high-dose methotrexate. They are suggested as useful guidelines in the prescription of high-dose methotrexate chemotherapy.

[Critical study of immunological assessment in cancer patients (author's transl)]. / Etude critique du bilan immunitaire de malades porteurs de cancers.

Immunological assessment of cancer patients has been suggested following the hypothesis of immune surveillance in cancer proposed by Burnet. This short review demonstrates that this hypothesis has not been confirmed by experimental data, this discrepancy with Burnet's hypothesis raising doubts as to the value of immunological assessment in cancer. Critical analysis of the various tests used shows that no specific test is currently available and that the value of non-specific tests is questionable. Finally, the analysis of more than eight thousand tests showed that they are of little aid in diagnosis, prognosis, or prediction of relapse, but that these tests could be useful in the follow-up of immunomodulation. Nevertheless, the availability of analysis of lymphocyte subpopulations by monoclonal antibodies could prove to be a new tool in the follow-up of these patients.