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Biomedical subjects

R Bugat

Publications and source records attributed to R Bugat.

At least 91 records · Page 5Linked to original sources
PubMed1991

Teniposide and cisplatin given by intraperitoneal administration: preclinical and phase I/pharmacokinetic studies.

Cisplatin and teniposide given by intraperitoneal (IP) route exert a synergistic therapeutic effect against ascitic P388 leukemia in mice. As single agents, they display different dose-limiting toxicities and favourable pharmacokinetic characteristics in IP phase I trials. We administered cisplatin (fixed dose: 200 mg/m2) and teniposide (escalating doses) by IP route without dwell-time to investigate the toxicity, pharmacokinetics and clinical activity of this 2-drug combination. Nine patients received a total of 14 courses. Myelosuppression, nausea and vomiting were the most frequent toxicities. Leukopenia was the dose-limiting toxicity. The maximum tolerated dose of teniposide was 100 mg/m2 when administered with a fixed dose of 200 mg/m2 cisplatin. Pharmacokinetic analysis showed that the main parameters of both cisplatin and teniposide in the peritoneum and in the plasma were not modified when the drugs were combined. It appears that a pharmacodynamic interaction exists between cisplatin and teniposide which results in increased hematologic toxicity. Although an objective response has been observed in one patient with refractory ovarian cancer, such association should not be applicable for further clinical development due to marked toxicity and the low dose of teniposide recommended.

Adult↗
PubMed1991

[Leiomyosarcoma of the inferior vena cava. General review apropos of a case].

The authors report a case of leiomyosarcoma (LMS) of the second segment of the inferior vena (IVC) with liver metastasis. Treatment by surgery and chemotherapy proved to be effective, as the patient is asymptomatic 8 years after the first operation. A review of the literature shows that these tumours are rare and have a slow course. The symptoms are often relatively minor and depend on the caval segment involved. The best examination for positive and topographic diagnosis remains computed tomography, but MR Imaging is promising. The prognosis remains severe (mean survival: 2 years) and surgery is the main treatment, with various techniques according to the caval segment involved.

Aged↗
PubMed1991

[Leiomyosarcoma of the inferior vena cava. Review of the literature apropos of a case].

The authors report a case of leiomyosarcoma (LMS) of the second segment of the inferior vena (IVC) with liver metastasis. Treatment by surgery and chemotherapy proved to be effective, as the patient is asymptomatic 8 years after the first operation. A review of the literature shows that these tumours are rare and have a slow course. The symptoms are often relatively minor and depend on the caval segment involved. The best examination for positive and topographic diagnosis remains computed tomography, but MR Imaging is promising. The prognosis remains severe (mean survival: 2 years) and surgery is the main treatment, with various techniques according to the caval segment involved.

Aged↗
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

Pharmacokinetics and toxicity of two modalities of etoposide infusion in metastatic non-small-cell lung carcinoma.

The pharmacokinetics and toxicity of two schedules of etoposide administration were studied in 19 patients suffering from metastatic non-small-cell lung cancer. Ten subjects received a 72-h continuous venous infusion (CVI) of 360 mg/m2 etoposide, and nine were given a daily dose of 120 mg/m2 for 3 consecutive days. In the two groups 80 mg/m2 cis-diamminedichloroplatinum (II) (CDDP) was infused on day 1. With CVI, the steady-state plasma concentration was reached 12-24 h after the start of the treatment. The plasma elimination rate showed a biexponential decay curve in both groups. No significant difference between total body clearance and the beta-phase volume of distribution was noted between the two modalities of administration. No relationship was found between biological and pharmacokinetic parameters.

Aged↗
PubMed1990

[Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases].

5-Fluorouracil (5FU) cardiotoxicity is thought to be an infrequent toxic effect, usually related to coronary vasospasm. Among 198 patients (pts) receiving 5FU as a continuous infusion (CI) over 96 or 120 h, at a daily dose of 1,000 mg/m2, 13 new cases of 5FU--cardiotoxicity are reported. In all cases but 1, cardiovascular symptoms occurred at the first 5FU-CI course, with mean time of onset of 3 d. Chest pain was the prominent inaugural symptom with angor pectoris (6 pts) and pericarditis (3 pts). Five pts developed cardiogenic shock, which was irreversible in 3 cases. The severity of such an evolution requires prompt 5FU discontinuation, if symptoms occur, and careful hemodynamic supervision during 5FU therapy. One patient experienced typical myocardial infarction, another one epicardo myocardiopathic process with adiastolia. Disorders of repolarisation on electrocardiographic tracing were the prominent abnormalities, associated with a significant increase of QT segment in 3 cases. Re-introduction of 5FU-CI resulted in chest pain recurrence in 2 out of 4 pts, despite calcium antagonist "prevention". In our retrospective study, the incidence of 5FU-CI cardiotoxicity is 6.5%, which is consistent with recent reports (10%). Whether 5FU-induced cardiotoxicity mechanism is related to vasospastic or direct effect remains unclear. However, our series suggests a 5FU-induced post ischaemic myocardial dysfunction as described in the "stunned myocardium" syndrome.

Adult↗
PubMed1990

[Phase II trial as 2nd line chemotherapy with 5 fluorouracil and cisplatin (5FU-CDDP) for advanced breast cancer].

Thirty patients with advanced breast cancer, previously treated with anthracycline and 5 fluorouracil in bolus administration, were evaluated with a chemotherapy regimen generally used in head and neck cancer. Treatment schedule consisted of: cisplatin 100 mg/m2 on d 1 and 5 fluorouracil 1000 mg/m2 continuous infusion on d 2-3-4-5 every 21 d. With all measurable lesions and 27 evaluable patients, the response rate was 29% (95% confidence interval: 12-47%), with 5 complete responses (3 soft tissue - 2 lung) and 3 partial responses (1 lung - 2 liver). The median duration of response is 4.5 months (range 2-11 months). The 30 patients (93 courses) are evaluable for toxicity. Hematologic toxicity was mild: anemia 68% grade 0, neutropenia 68% grade 0 and thrombocytopenia 83% grade 0. Nausea and vomiting were severe 83% grade 3 + 4 at d 1. Others side effects were mild including 5/91 mucositis grade 2 + 3, peripheral neuropathy 1/31 grade 2 and 2/91 reversible rise in serum creatinine greater than 1.5 mg/dl.

Adult↗
PubMed1990

[Role and results of radiotherapy in the treatment of pancreatic adenocarcinoma].

Most pancreatic carcinomas are clinically observed when the tumoral spread is well advanced. Consequently, surgical excision is very often either partial or unfeasible. However, evolutive patterns of pancreatic carcinomas show a long past history of loco-regional spread before the onset of visceral metastasis. Consequently, radiotherapy could be proposed to treat locally advanced pancreatic tumors or residual disease after surgical excision in curative intend. The major challenge dealing with radiotherapeutic management of pancreatic carcinomas is to safely deliver doses as high as 60-70 Gy into the upper half of the abdominal cavity. Several technical conditions must be fulfilled before this can take place: high energy and multiple convergent photon beams, precise surgical and/or radiological description of tumoral extent, careful sparing of critical tissues such as spinal cord and kidneys. Usually, radiotherapeutic planning is administered in 2 successive sessions: 40-45 Gy are first administered to the tumor and main nodal drainage over 4-6 weeks, then a 15-25 Gy boost dose is given to the primary tumor bed only. However, postoperative irradiation after complete removal of a gross tumor gives a 10% survival rate only at 2 years. Improvement of these results, are eventually expected from intra-operative irradiation techniques or radiochemotherapy combined treatments.

Adenocarcinoma↗
PubMed1989

A pharmacokinetic model for intraperitoneal administration of drugs: application to teniposide in humans.

A pharmacokinetic study of teniposide after ip administration with a 4-h dwell time was performed in patients suffering from abdominal malignant ascites. A three-compartment open model was developed to fit together the data obtained in plasma and peritoneum. The pharmacokinetic parameters obtained by the model agreed with those obtained by model-independent analysis, and the fitting correctly depicted the plasma and peritoneal concentration decays. According to the results, such a model could be applied to ip administration of anticancerous drugs.

Adolescent↗
PubMed1989

300 mg/m2 carboplatin (Cb), adriamycin (A) cyclophosphamide (C) (CACb-300) combination in advanced ovarian carcinoma: a feasibility study.

Carboplatin (Cb) is an active drug in ovarian carcinoma that has fewer visceral side effects than cisplatin (CDDP) but higher myelotoxicity, which makes it difficult to combine at efficient doses with other myelotoxic drugs. In a preliminary study in advanced ovarian carcinoma, Rosso et al. showed the maximum tolerated dose of Cb given in combination with cyclophosphamide (C) and adriamycin (A) to be 200 mg/m2. Since the efficacy of Cb may be dose-dependent, as is that of CDDP, we started a feasibility study of a CACb-300 regimen, that is, using Cb at 300 mg/m2 with lower C and A doses. Our data shows that the CACb-300 combination can safely be given in previously untreated patients for at least six 28-day cycles.

Adenocarcinoma↗
PubMed1989

Phase I/pharmacokinetic study of intraperitoneal teniposide (VM 26).

A phase I/pharmacokinetic study of the i.p. administration of teniposide (VM 26) was undertaken. Eighteen patients with various malignancies and refractory malignant ascites consented to enter this trial. The dose escalation was made according to the modified Fibonacci scheme. Twenty-four courses were evaluable for toxicity, response and pharmacokinetics. The maximum tolerated dose was reached at 450 mg/m2 and the limiting toxicity was myelosuppression, principally leukopenia. Abdominal pain occurred in one half of the courses but was not limiting. No partial remission, but two 'no change' were achieved for more than 2 months. A reduction or disappearance of ascites was seen in two patients. Pharmacokinetic studies, carried out in all courses, showed that the total exposure for peritoneal cavity averaged 10-fold greater than that of plasma. Based on the outcome of this phase I study, we could recommend phase II studies at a dose of 390 mg/m2 i.p. repeated every 4 weeks with a 4 h dwell-time.

Abdominal Neoplasms↗
PubMed1989

Clinical and pharmacokinetic study of 96-h infusions of doxorubicin in advanced cancer patients.

A phase I and a pharmacokinetic study of 96-h infusions of doxorubicin were performed in order to evaluate the maximum tolerated dose with this schedule of administration. Seventeen patients suffering from a digestive carcinoma were included in the study and a total of 71 courses of treatment were performed. The starting dose was 15 mg/m2/day and was increased in 2.5 mg/m2/day increments. The main toxicities observed were neutropenia and mucositis, which became limiting from 22.5 mg/m2/day (90 mg/m2 over a 96-h period); this dose was therefore defined as the maximal tolerated dose. No objective response to treatment was observed. For further studies, the recommended dose should not exceed 20 mg/m2/day. A plasma plateau concentration of doxorubicin was reached within 24 h. Despite a constant infusion rate, the plasma concentration of doxorubicin showed transient variations in several patients. However, an average plasma concentration could be evaluated for 33 courses of treatment, and this was linearly related to the dose. Doxorubicinol was the only detected metabolite of doxorubicin and its plasma concentration progressively increased throughout infusion. A detailed pharmacokinetic study was performed in 13 courses of treatment. The mean plasma clearance of doxorubicin was 25.2 l/h/m2 and the mean terminal half-lives of doxorubicin and doxorubicinol were respectively 43.6 and 66.2 h. Urinary excretion of doxorubicin plus metabolite was regular from the 24th to the 96th hour of infusion; however, the proportion of doxorubicinol progressively increased in urine. The protracted half-life of this metabolite probably explains its accumulation during infusion.

Adult↗
PubMed1989

Cytotoxic effects of teniposide combined with cis-diammine-dichloroplatinum (II) on the in vitro Lewis lung carcinoma model: influence of the treatment schedule.

The interactions between cis-diammine-dichloroplatinum (CDDP) and teniposide (VM26) have been studied in vitro on a Lewis lung carcinoma culture in terms of span, order of exposure or time delay between both drugs. When the cells were simultaneously exposed to VM26 and CDDP for 24 h, a supra-additive effect was observed (P less than 0.001). When the cells were first incubated with VM26, the cytotoxicity was emphasized (P less than 0.02), whereas after a prior exposure to CDDP, only an additive effect was noticed. For a short exposure to the drugs (1 h), we noticed an enhancement of the cytotoxic effect when the cells were first exposed to VM26, principally when the time delay between epipodophyllotoxin and CDDP was 0 or 1 h (P less than 0.001). The sequence in which VM26 was given before CDDP induced a significant increase of the cytotoxic effect, whatever the span of exposure.

Antineoplastic Combined Chemotherapy Protocols↗