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Biomedical subjects

D Cupissol

Publications and source records attributed to D Cupissol.

At least 19 recordsLinked to original sources
PubMed1995

Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.

PURPOSE: This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy. PATIENTS AND METHODS: Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner. RESULTS: Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles. CONCLUSION: Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.

Adult↗
PubMed1994

Inhibition of dihydropyrimidine dehydrogenase by alpha-interferon: experimental data on human tumor cell lines.

Interferons (IFNs) are very promising fluorouracil (FU) biochemical modulators. The pharmacological origin sustaining the FU-IFN synergistic interaction is not clearly understood. It was recently shown that alpha-IFN was associated with a dose-dependent decrease in FU clearance in treated patients. Dihydropyrimidine dehydrogenase (DPD) is the key regulating enzyme for FU catabolism. The effects on DPD exerted by both the IFN dose and the duration of exposure were evaluated in a panel of five human cancer cell lines. All cell lines investigated exhibited quantifiable DPD activity with inter-cell-line variability (0.118-0.318 nmol min-1 mg protein-1). A prolonged exposure to IFN (up to 5 days) was necessary to obtain a significant inhibition of DPD activity. A concentration-dependent significant decrease in DPD activity, reaching 50% of the initial activity determined for the highest IFN concentration (10(5) IU/ml), was demonstrated in all cell lines tested (5-day IFN exposure). For three cell lines, IFN potentiated the FU-induced growth inhibition in a concentration-dependent manner. Considering all cell lines and all IFN concentrations, it appears that globally, the greater the inhibition of DPD activity, the greater the FU potentiation (Spearman rank correlation on all cell lines, P = 0.011).

Carcinoma↗
PubMed1994

A double-blind, randomised, crossover comparison of granisetron and ondansetron in 5-day fractionated chemotherapy: assessment of efficacy, safety and patient preference. The Granisetron Study Group.

We report the first double-blind, randomised, crossover study comparing granisetron and ondansetron as antiemetics in cancer chemotherapy. Patients receiving two cycles of identical chemotherapy fractionated over 5 days were given either granisetron (3 mg/day) or ondansetron (24 mg/day) on each day of chemotherapy, using a double-dummy technique to preserve study blindness. Patients then crossed over to the other therapy. 309 patients (237 male) completed the crossover: 260 received cisplatin (mean dose 19.2 mg/m2/day) and 49 received ifosfamide (mean dose 1415 mg/m2/day). Primary efficacy variables were prospectively defined as complete response (no vomiting and mild or absent nausea) over 5 days, and patient preference. Both agents achieved good control of emetic symptoms with 5-day complete response rates of 44.0% on granisetron and 39.8% on ondansetron [95% confidence interval (CI) for odds ratio 0.8, 1.9]. Complete response rates were very similar in patients receiving either cisplatin (40.8% granisetron, 37.6% ondansetron) or ifosfamide (61.2% granisetron, 51.0% ondansetron). There was a statistically significant difference in patient preference in favour of granisetron, 105 patients preferred granisetron, 79 preferred ondansetron, 121 had no preference (P = 0.048: 95% CI for odds ratio 1.00, 1.84). Single daily doses of granisetron (3 mg/day) appeared similarly effective and well tolerated to three daily doses of ondansetron (8 mg three times daily) in prevention of emesis induced by 5-day fractionated chemotherapy, however, significantly more patients preferred granisetron.

Adolescent↗
PubMed1993

Evaluation of the bioequivalence of tablet and capsule formulations of granisetron in patients undergoing cytotoxic chemotherapy for malignant disease.

Granisetron is a novel, highly specific 5-hydroxytryptamine receptor antagonist given prophylactically to patients undergoing chemotherapy. An open, randomized, crossover trial was performed with 37 patients (24 females and 13 males) undergoing cytotoxic chemotherapy for malignant disease to compare an oral tablet (1-mg tablet given twice daily) with a clinical-trial capsule (1-mg capsule given twice daily). Complete pharmacokinetic data were determined for 24 patients (14 females and 10 males). The concentration of granisetron in plasma was measured by HPLC; the limit of quantitation was 0.2 ng/mL. The bioavailability evaluation was based mainly on the area under the curve (AUC) (mean values: 52.1 ng.h/mL for the capsule and 54.2 ng.h/mL for the tablet) and the maximum concentration (Cmax) (mean values: 7.42 ng/mL for the capsule and 8.18 ng/mL for the tablet) measured at the steady state after 7 days of continuous therapy. Wide interpatient variability in plasma granisetron levels after oral administration was observed. The 90% standard confidence interval for the geometric mean ratio overlapped the critical range, 0.8-1.25. Point estimates for AUC and Cmax based on two one-sided t tests and log-transformed data showed that the upper limit of the confidence interval was not within 20% of the mean for the capsule; the corresponding power analysis values for AUC and Cmax were 0.89 and 0.81, respectively. Despite bioequivalence not being proven, any differences that exist between the two formulations are likely to be small. There was no difference in efficacy or safety between the two formulations assessed.

Adolescent↗
PubMed1993

[Ultradian variations of interleukin-1 beta concentration (IL-1 beta), interferon gamma (IFN-gamma) and soluble IL-2 receptors (RIL-2) in healthy volunteers humen].

The aim of this study consisted in underlining the concentrations' evolution in time of two cytokines: IL-1 beta and IFN-gamma, as well as that of RIL-2 (soluble receptor for IL-2), in healthy volunteers. Under normal physiological conditions, these molecules are secreted in small amounts, according to a sequential chronology. Thus, 25 blood samples were carried out from each of the four subjects included in the study, one every 20 minutes, during 8 hours. Concentrations were determined with the ELISA method. Spectral analysis was carried out using the Frequencies Spectrum method (Fourier Transform of a temporal series). This method allows a rhythm search over a milited number of values, in a short interval of time, provided having enough samples. Important variabilities have been observed between all subjects sera, particularly for IL-1 beta (Range (mean +/- SD): 132 +/- 34.6 pg/ml to 250 +/- 17.5 pg/ml, one subject had low values: 2.34 +/- 0.53 pg/ml) and RIL-2 (Range: 677 +/- 175 pg/ml to 1,187 +/- 46.2 pg/ml). Furthermore, ultradian serum variations, characterized by the relation ((Cmax-Cmin)/Cmax) x 100, have been assessed for each subject and each molecule: IL-1 beta (Range: 18.9 to 92.2%), IFN-gamma (Range: 66.3 to 74.2%) and RIL-2 (Range: 11.6 to 86.3%); they might be the manifestation of a periodicity; this hypothesis has been confirmed by the spectral analysis. Thus, the concentrations' variation with time showed a periodicity (Range: 80 mn to 240 mn, the most frequent period was 160 mn (2 h 40 mn)).

Activity Cycles↗
PubMed1992

Fotemustine plus dacarbazine for malignant melanoma.

119 patients with metastatic melanoma received fotemustine 100 mg/m2 on days 1 and 8 and dacarbazine 250 mg/m2 on days 15-18. After a 5-week rest, fotemustine 100 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 2-5 was given every 3-4 weeks. 12 complete responses (11.6%) and 16 partial responses were observed in 103 evaluable patients (response rate 27.2%). The median duration of response was 21.5+ weeks (8+ to 53+). The response rate was 26.3% in CNS, 18.2% in visceral sites and 37.5% in non-visceral sites. The toxicity was mainly haematological: grade III-IV leukopenia in 27.4% and thrombocytopenia in 23.4%. The response rate was lower than that in 63 patients previously reported. The present series had a higher median age (54 vs. 40 years) without any differences in other population variables. However, activity on CNS metastases and on non-visceral sites was confirmed. Haematological toxicity was about 50% lower than that with fotemustine alone. Hence, this is an active outpatient regimen for metastatic melanoma, especially against cerebral and non-visceral metastases.

Adult↗
PubMed1990

Combination chemotherapy of dacarbazine and fotemustine in disseminated malignant melanoma. Experience of the French Study Group.

A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.

Adult↗
PubMed1990

Tumor-tissue and plasma concentrations of platinum during chemotherapy of non-small-cell lung cancer patients.

Tumor-tissue and plasma concentrations of platinum were studied prospectively in two groups of eight patients who were suffering from advanced non-small-cell lung cancer. Treatments including two different schedules of cisplatin administration (25 vs 100 mg/m2 on day 1) were compared. At 30 min after the beginning of the cisplatin infusion, blood samples and bronchoscopically obtained biopsy specimens were taken for determinations of platinum concentrations by means of flameless atomic absorption spectrophotometry. The procedure did not induce any complication. Total plasma platinum concentrations at 30 min were significantly lower (P less than 0.01) in patients receiving 25 mg/m2 (0.49 +/- 0.23 microgram Pt/ml) than in those receiving 100 mg/m2 (1.44 +/- 0.62 micrograms Pt/ml), whereas no significant difference was observed in tumor-tissue platinum concentrations (22.49 +/- 53.89 ng Pt/mg in patients receiving 25 mg/m2 vs 51.13 +/- 65.52 ng Pt/mg in those receiving 100 mg/m2). There was a weak correlation between simultaneous plasma and tumor-tissue platinum concentrations at 30 min. Tumor-tissue platinum concentrations seem to be poorly influenced by the cisplatin dose. This finding suggests a great interindividual variability of platinum tumor-diffusion properties in non-small-cell lung cancer.

Adult↗
PubMed1989

[Prevention of cisplatin nephrotoxicity in cancer: adjusting the dosage with a computerized chrono-pump].

Platinum and its derivates are particularly efficient in treatment of ovarian and testis carcinomas. Nevertheless, the high nephrotoxicity of these drugs limits their use. It is known that nephrotoxicity appears when platinum plasmatic concentrations are higher than 1.5 mg/l. Moreover, the wide variability between patients and between cures, emphasizes the difficulties of utilization. Using a computerized pump and a program for individual dosage regimen, an efficient prevention of plasmatic overdosages have been realised and nephrotoxicity accidents have been avoided.

Aged↗
PubMed1984

Increased sensitivity of IL2-dependent cultured T cells and enhancement of in vitro IL2 production by human lymphocytes treated with Bestatin.

Bestatin is an inhibitor of leucine aminopeptidase and aminopeptidase B which potentiates various immune functions, such as delayed hypersensitivity and antibody formation, and inhibits tumor cell growth in animal models. Our study focuses on the effect of Bestatin on interleukin 2 (IL2) sensitivity of IL2-dependent cultured T cells (CTC) and on IL2 production by human peripheral blood mononuclear cells (PBM). Bestatin (0.01 - 10 micrograms/ml) increases CTC 3H-TdR incorporation in the presence of suboptimal (low) concentrations of exogenous IL2. Bestatin alone has no mitogenic effect on CTC. This phenomenon is due to increased CTC IL2-receptors after treatment with Bestatin. Bestatin (1 - 10 micrograms/ml) also increases (1.4 - 21 fold) IL2 production by PHA-stimulated PBM. Bestatin therefore increases both IL2 sensitivity and IL2 production. This may explain the various immunopotentiating effects of Bestatin previously described.

Adjuvants, Immunologic↗
PubMed1983

Modulation of human T lymphocyte functions by isoprinosine.

Isoprinosine was shown to alter certain T cell functions. In vitro, it has previously been shown to induce suppressor cell activity in both mouse and human lymphocytes. Our in vitro results suggest that Isoprinosine acts on immune balance by increasing the number of non-suppressor T cells and, at least partially blocks Con A induced suppressor activity. In vitro NK activity remained unaltered.

Adjuvants, Immunologic↗
PubMed1982

[Evaluation of a new antiemetic, alizapride, in cancerology (author's transl)].

The antiemetic effect of alizapride was evaluated in 50 patients with advanced cancer undergoing chemotherapy with cis-platinum. Our results suggest that alizapride, in a dose of 800 or 900 mg, significantly alleviates nausea and emesis. In a preliminary study, we had established that, without antiemetic therapy, the same patients all suffered from emesis. On the whole, alizapride was well tolerated ; no major side-effects were recorded.

Adult↗
PubMed1982

Follow-up of a randomized trial for oat cell carcinoma evaluating the efficacy of peripheral intravenous nutrition (PIVN) as adjunct treatment.

A randomized trial was initiated to compare the effects of peripheral i.v. nutrition (PIVN)-associated chemotherapy (adriamycin, vincristine, VP-16-213, and cyclophosphamide) versus a chemotherapy control group in patients with oat cell lung carcinoma. Thirty-nine evaluable patients were randomized. The test group included 19 patients, whereas 20 were followed in the control group. PIVN was scheduled each day the patient underwent chemotherapy. Each patient received 1,550 kcal day which included 10% glucose, 20% lipids, and amino acids which may or may not have been mixed in the same infusion bottle. The results show ten PIVN patients presently in complete remission at the end of three courses of treatment, compared to nine over the same time period in the chemotherapy control group. Thirty-three percent of patients are still alive after 15 months after the beginning of treatment. There was no significant difference in either general health or side effects, frequency or duration of complete remission, or survival time. After 1 year of treatment, 8 of 19 PIVN patients are still in complete remission, compared to 7 of 20 patients in the control groups.

Carcinoma, Small Cell↗
PubMed1982

Decrease of tumor growth in mice after intravenous thymosin-treated bone marrow cell injection.

The effect of iv injection in C57BL/6 mice of 3X10(7) bone marrow cells preincubated in either thymosin fraction V or thymosin alpha-1 was evaluated on the growth of a 3-methylcholanthrene-induced transplantable tumor in a syngeneic system. The effect was then compared to that elicited by theophylline or levamisole, which both demonstrated thymosin-like action in vitro. The results showed significantly retarded tumor growth (P less than 0.001) and prolonged survival time (P less than 0.001) when thymosin fraction V was used. The same results were obtained with thymosin alpha-1 with use of the same protocol but only one-twentieth of the concentration of fraction V. Theophylline and levamisole demonstrated no antitumor effect.

Animals↗
PubMed1982

Prognostic evaluation of human tumor cell in vitro cloning assay.

In vitro cloning of human tumor cells were carried out for 19 patients: 13 breast cancers (4 metastatic effusions and 9 primary tumors), 3 ovarian cancers, 2 glioblastomas and 1 meningioma. Cloning efficiency varied from 1 X 10(-5) to 2.8 X 10(-3). Tumor cells with the highest cloning rates were provided by patients with rapidly evolving tumors. 7 drug assays were performed: in vitro-in vivo correlation was observed in all cases (drug resistance in 5 cases: drug sensitivity in 2).

Cell Count↗