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Biomedical subjects

D Khayat

Publications and source records attributed to D Khayat.

At least 55 records · Page 3Linked to original sources
PubMed1997

A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy.

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (> or = 80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.

Acute Disease↗
PubMed1997

A phase II study of cisplatin, 5-fluorouracil, leucovorin, and etoposide in advanced non-small-cell lung cancer.

The aim of this study was to define the efficacy of a combination of cisplatin, 5-fluorouracil (5-FU), leucovorin, and etoposide (VP-16) in locally advanced or metastatic non-small-cell lung cancer (NSCLC). From September 1991 to November 1994, 28 patients were treated with cisplatin, 100 mg/m2 i.v. on day 1; 5-FU and leucovorin, 500 mg/m2 on days 1, 2, 3, and 4 by i.v. continuous infusion; and VP-16, 70 mg/m2 i.v. on days 1, 2, 3, and 4 (combination, PFL-VP-16). Cycles were repeated every 3 weeks. There were 22 men and six women. The median age was 58 (range, 41-76). All had measurable diseases (one was stage IIIA, six were IIIB, and 21 were IV). None had previously received chemotherapy for metastatic disease. There was one complete response and six partial responses, for an overall response rate of 25% (95% confidence interval 9-41%). The median response duration and the overall survival were 8 and 9 months, respectively. Limiting toxicity was myelosuppression and oral mucositis. Grade 3 or 4 leucopenia was observed in 20% of all of the 95 cycles administered, and oral mucositis in 13%. No grade 3 or 4 renal toxicity occurred, and neurologic toxicities were limited (3% of the 28 patients experienced grade 3). PFL-VP-16 is active and can easily be administered to patients with advanced NSCLC. However, according to the results obtained with this schedule, VP-16 does not increase either response rate or survival compared with the regimen previously described by Vokes et al. (PFL).

Adult↗
PubMed1997

Preliminary results of a phase I/II study of paclitaxel, cisplatin, and cyclophosphamide in advanced ovarian carcinoma.

The clinical activity and toxicity of the triple combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), cyclophosphamide, and cisplatin was assessed in both previously treated and untreated women with advanced ovarian carcinoma. Paclitaxel 175 mg/m2 was administered over 3 hours following standard premedication (prednisolone, dexchlorpheniramine, and cimetidine). Cisplatin 80 mg/m2 and cyclophosphamide 600 mg/m2 were given 6 to 12 hours after paclitaxel. Treatment was given at 3-week intervals for six cycles. Twenty-seven patients entered the study; 23 were evaluable for toxicity and 17 for response. Paclitaxel appeared to add additional efficacy to the standard cisplatin/cyclophosphamide regimen. Both the overall and complete remission rates were very high (88% and 70%, respectively), and histologically confirmed complete remissions exceeded 60%. Longer follow-up is needed to determine the duration of these responses. The primary toxicities included leukoneutropenia, peripheral neuropathy, asthenia, and alopecia. Only two of 23 patients withdrew because of toxicity, however, and only two treatment cycles were complicated by neutropenic fever requiring intravenous antibiotics. No life-threatening toxicities were encountered, although the peripheral neuropathy was poorly and slowly reversible and may have a significant impact on the patients' quality of life.

Adult↗
PubMed1997

A phase II trial of gemcitabine and ifosfamide in non-small cell lung cancer.

The novel nucleoside agent gemcitabine has demonstrated antitumor activity against a variety of solid tumors and is associated with low toxicity. A phase I trial in Germany of gemcitabine combined with the alkylating agent ifosfamide has shown encouraging activity against non-small cell lung cancer (NSCLC). The efficacy and toxicity of this combination was further evaluated in a phase II trial of chemotherapy-naive patients with NSCLC (mostly stage IV disease). Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and 15 followed by a 1-week rest, while ifosfamide was given at a dose of 1,500 mg/m2 on day 8 and days 9 through 12. Fifty-one of 56 patients were evaluable for response. Eleven partial responses were seen, for an overall objective response rate of 22%. The 6- and 9-month survival rates are 62% and 41%, respectively. Grade 3 and 4 neutropenia occurred in 35.8% and 24.5% of patients, respectively, but the incidence of infection was low. These results indicate that the combination of gemcitabine and ifosfamide is active against NSCLC and has a mild toxicity profile, and suggest that further evaluation of this combination is warranted.

Adult↗
PubMed1997

Docetaxel in combination chemotherapy for metastatic breast cancer.

Due to its novel mechanism of action, docetaxel has significant in vitro activity against a variety of solid tumors, including breast cancer. In phase II clinical trials, docetaxel 100 mg/m2 every 3 weeks has shown substantial single-agent activity in patients with both previously untreated and heavily pretreated metastatic breast cancer. As single-agent chemotherapy is rarely curative in this setting, docetaxel has been combined with other anticancer agents with proven efficacy against breast cancer (doxorubicin, vinorelbine, fluorouracil, cyclophosphamide, cisplatin, and doxorubicin plus cyclophosphamide) in an attempt to increase efficacy and prolong patient survival. The aims of these phase I dose-finding studies were to define the maximum tolerated dose, the dose-limiting toxicity, the recommended dose, and the safety profile of each combination. All patients had previously untreated metastatic breast cancer. Each study followed a dose-escalation design; patients were initially assigned to the lowest dose level, with at least three patients treated at each level before enrolling patients at the next level. All patients received corticosteroid-based premedication, but granulocyte colony-stimulating factor was not routinely used. The docetaxel/doxorubicin and docetaxel/ vinorelbine studies have been recently completed; in both studies, the dose-limiting toxicity was neutropenia. Other adverse events were generally mild. No significant cardiotoxicity (with docetaxel/doxorubicin) or neurotoxicity (with docetaxel/vinorelbine) was observed, and no patients discontinued treatment because of fluid retention. Both combinations are well tolerated without granulocyte colony-stimulating factor support. The recommended dose for docetaxel/doxorubicin in phase II studies is either 75/50 or 60/60 mg/m2 administered on day 1 every 3 weeks; impressive response rates of 90% and 66%, respectively, were achieved with these dose levels. The recommended dose for docetaxel/vinorelbine is docetaxel 85 mg/m2 on day 1 and vinorelbine 20 mg/m2 on days 1 and 5, repeated every 3 weeks; the efficacy of this combination is still being evaluated, but preliminary results are promising. For both combinations, the time to disease progression and median response duration were not available at the time of this report. Combination studies with fluorouracil, cisplatin, and cyclophosphamide, and a study of sequential administration with doxorubicin + cyclophosphamide, are ongoing. Interim results indicate that these docetaxel-based combinations have acceptable safety profiles and encouraging levels of antitumor activity. The full results of these studies will help to elucidate the potential contribution of docetaxel-based combination chemotherapy to the management of metastatic breast cancer.

Antineoplastic Agents↗
PubMed1997

[Value of the combination of oral ondansetron with methylprednisolone as soon as the first cure in mild emetogenic chemotherapy. Groupe français d'étude de l'ondansétron].

This multicentre randomized single-blind parallel group study compared the efficacy of oral ondansetron plus methylprednisolone (OND+MPS) with conventional antiemetic strategies (TH) over 4 consecutive courses in moderately emetogenic chemotherapy. This study was conducted in naive patients receiving a minimum of 3 cytotoxics including adriamycin (> or = 35 mg/m2) and cyclophosphamide (> or = 500 mg/m2) plus an other alkylating agent. Of the 364 patients included in the study, 70% had a breast cancer and 30% a lymphoma. Patients were divided into two groups. On day 1, one group of patients received OND (8 mg, po) 2 hours before chemotherapy, followed by a slow intravenous injection of MPS (120 mg) 30 minutes before chemotherapy. Eight hours after the start of chemotherapy, patients received OND (8 mg, po) and MPS (16 mg, po). On days 2-4, patients received OND (8 mg, po) and MPS (16 mg, po) twice daily. The second group of patients received conventional antiemetic treatment (benzamide plus corticosteroids with or without benzodiazepins). The primary efficacy parameter was defined as complete control of emesis (0 emetic episodes) over 4 consecutive courses of chemotherapy. In the OND+MPS group, 63% of patients experienced complete control of emesis versus 33% in the TH group (p < 0.001). The secondary parameters (percentage of days with no emetic episodes, control of emetic episodes, grade of nausea at each course, patient preference and quality of life evaluation) were always significantly better in the OND+MPS treated group. The percentage of days without any emetic episode over the 4 courses of chemotherapy was 91% in the OND+MPS group and 75% in the TH group (p < 0.001). Ninety-two percent of patients from OND+MPS group preferred to continue their treatment versus 76% in the TH group (p < 0.001). Concerning the quality of life assessed by FLIC and FLIE questionnaires, the analysis showed a significant difference at the end of the treatment in favor of OND+MPS (p = 0.037 and 0.0075 respectively). This study showed the interest in using the combination OND+MPS right from the first course of moderately emetogenic chemotherapy.

Adult↗
PubMed1997

Salpêtrière Hospital experience with biochemotherapy in metastatic melanoma.

PURPOSE: This article investigates the safety and efficacy of a simple cisplatin-based biochemotherapy regimen, containing single-agent cisplatin plus recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha), in the treatment of metastatic melanoma. PATIENTS AND METHODS: Between December 1990 and April 1997, 129 patients were treated with cisplatin (100 mg/m2, day 0) plus continuous intravenous infusion rIL-2 (18 MIU/m2/day, days 3-6 and days 17-21) and subcutaneous rIFN-alpha (9 MIU three times per week) plus or minus tamoxifen (160 mg/day) on three different protocols. Tumor response, disease-free survival, and overall survival were evaluated for all evaluable patients (N = 127). RESULTS: The overall response rate was 49%, and 10% of patients achieved a complete response. Responses were observed at all sites of metastases. In one case, a patient with a large cutaneous inguinal mass experienced a dramatic regression of that lesion within 1 month. The median disease-free survival was 5 months, and median overall survival was 11 months. Patients who responded had a significant survival advantage over nonresponders, and patients who achieved a complete response had a significant survival advantage over patients with a partial response. Toxicities were manageable and reversible upon discontinuation of therapy. CONCLUSION: The response rates achieved with this simple biochemotherapy regimen are comparable to those for other cisplatin-based biochemotherapy regimens, which use more complex multiagent chemotherapy regimens. We found no added clinical benefit from the addition of tamoxifen to cisplatin.

Adolescent↗
PubMed1996

[Chemotherapy and immunotherapy of metastatic malignant melanomas].

Prognosis in metastatic malignant melanoma is poor because of chemo and radiotherapy resistance. However, some drugs, such as dacarbazine, cisplatinum or fotemustine, a new nitrosourea, have produced a response rate of more than 20%. Combining these drugs increases response rate to 30-40%. Immunotherapy by interferon-alpha 2 shows about 15-20% response rate but interleukin-2 would be more effective especially in combination with cisplatinum and interferon-alpha 2 with 50% response and long survival after cessation of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Complete remission seven years after treatment for metastatic malignant melanoma.

BACKGROUND: In this study, the authors identified seven-year survivors after completion of the French multicenter Phase II trial of fotemustine for the treatment of metastatic malignant melanoma. METHODS: One hundred sixty-nine patients with metastatic malignant melanoma were included in this Phase II study. One hundred fifty-three patient records were evaluable with an overall response rate of 24.2%. RESULTS: Five of these patients are alive and in complete remission. One patient had a complete response after fotemustine administration and then relapsed. One patient had a partial response. Three patients had stable disease. These five patients underwent surgery for relapse or residual disease and subsequently achieved durable complete remission. CONCLUSIONS: Long term survival may be the outcome after surgical resection of residual metastatic melanoma after chemotherapy.

Antineoplastic Agents↗
PubMed1996

Anti-Fc gamma receptor autoantibodies from patients with Sjögren's syndrome do not react with native receptor on human polymorphonuclear leukocytes.

Sera from patients with primary Sjögren's syndrome (pSS) have been examined for the presence of cell-free Fc-gamma receptor (Fc gamma R) IIIb, which is expressed in polymorphonuclear leukocytes (PMN), and the production of related autoantibody. Sera from 66 patients with pSS were evaluated by an ELISA using recombinant human Fc gamma RIIIb as the substrate and by flow cytometry. Cell-free Fc gamma RIIIb was also detected by an ELISA. The fine specificity of autoantibodies was established by inhibition with a preparation of Fc gamma RI plus Fc gamma RII, and two ELISAs using Fc gamma RI and Fc gamma RII as the substrates respectively. Anti-Fc gamma RIIIb activity was found in 30 patients (45%), but 25 of them did not react with autologous PMN, whereas they bound to Fc gamma RIIIb eluted from the same PMN in ELISA and Western blotting. Autoantibodies from one serum recognized the three receptors, six with Fc gamma RII in addition to Fc gamma RIII, and three sera were specific for the latter receptor. None of these reacted with Fc gamma RI- and Fc gamma RII-carrying cells. Cell-free Fc gamma RIIIb, but negligible amounts of Fc gamma RIIIa, were detectable in the patient sera. The membrane expression of CD15, an early activation marker, was diminished, while that of three PMN late activation markers was markedly enhanced. Taken together, these results suggest that autoantibodies are produced following the shedding of Fc gamma RIIIb upon PMN activation. A credible candidate for this activation is IgG-containing immune complexes.

Adult↗
PubMed1996

Virtual tracheo-bronchial endoscopy: educational and diagnostic value.

The use of Helical CT significantly improves image quality of examinations in a number of clinical settings. It is particularly suited to the study of the tracheo-bronchial tree as a result of new ways of image processing (developed by GEMS research) which can produce virtual endoscopic images without the use of an endoscope. We present our initial anatamo-radiological findings and their educational value as well as our thoughts on potential future clinical applications.

Anatomy↗
PubMed1996

The clinical measurement of volumes using helical CT.

The object of this preliminary study is to evaluate the new techniques of measurement by helical CT which allow direct assessment of the volume of a lesion in clinical practice particularly by obtaining direct macroscopic anatomical correlation. Its primary application is anatomical, with measurement of the volumes of organs or anatomical structures, the clinical importance of which relates primarily to oncology. We present our initial results, including their applications and limits, before extending this study to a larger series so that it may be compared with other multicentre evaluations.

Feasibility Studies↗
PubMed1996

Comparison of the uptake of retinoids 13-cis-retinoic acid and Ro 13-6298 delivered to HL-60 cells by serum albumin or low-density lipoprotein.

Retinoids, a class of polyisoprenoids including retinol and retinoic acid, regulate and control diverse physiological functions via their cell-differentiating and morphogenic potential. In the present study we showed that the extracellular concentration of retinoid-binding proteins such as albumin limits the amount of retinoid entering the human promyelocytic leukemia cell line HL-60. These cells accumulate 5 -10 times more retinoid when delivered free in solution than when bound to either albumin or low-density lipoprotein (LDL). Moreover. the effect of protein binding is concentration-dependent, with a higher concentration of binding protein corresponding to a lower level of cellular uptake. Furthermore, the uptake of the ester derivative is higher than that of the acidic retinoid. These observations suggest that (a) the cellular uptake of both retinoids occurs via the free form of the ligand in solution, with the free concentration of ligand decreasing as the carrier-protein concentration increases, and (b) according to a passive mechanism, the ester derivative, unionized and lipophilic, enters the cells more easily than does the acidic derivative.

Antineoplastic Agents↗
PubMed1996

European School of Oncology European consensus on the use of granulocyte colony-stimulating factor: the example of breast cancer.

An apparent chemotherapeutic dose-response relationship for patients with breast cancer has provided clinicians with the impetus to investigate further the usefulness of dose-intensification strategies in this setting. These approaches have provided promising results: noticeable improvements in response rates in terms of disease-free survival have been recorded, particularly when dose intensification has been used as first-line consolidation therapy for chemosensitive advanced disease and as consolidation in adjuvant therapy for high-risk patients. It may also be of use in the treatment of inflammatory and locally advanced disease. Although the results of prospective studies will help to define the potential advantages of dose-intensification strategies further, comparisons of myeloablative and subablative intensification regimens are needed to define the role of dose and dose intensity in this setting.

Antineoplastic Agents↗
PubMed1996

Direct gene transfer of a plasmid carrying the herpes simplex virus-thymidine kinase gene (HSV-TK) in transplanted murine melanoma: in vivo study.

The aim of the study was to use a virus-free system to transfer the Herpes Simplex Virus-thymidine kinase (HSV-TK) gene in mice bearing melanoma tumours. B16 F1 murine melanoma cells were injected subcutaneously. On days 11 and 14, an intratumoral injection of either naked plasmid containing the HSV-TK gene (pAG0) or pAG0-lipofectamine complexes was given. Ganciclovir (120 mg/kg/day) was given for 5 days starting on day 14. Tumour weight reduction (40-50%) was observed in treated animals versus different control groups. Moreover, histopathological analysis on tumours showed large areas of cavitary necrosis (85%) in treated groups compared to controls (10%). Using a simple and safe method, the results presented here demonstrated that virus-free mediated delivery of the HSV-TK gene is efficient in vivo in murine malignant melanoma.

Animals↗