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O Rixe

Publications and source records attributed to O Rixe.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Platinum salts: cytotoxic mechanisms of action, mechanisms of resistance of cancer cells, interactions with ionizing radiation, specificity of carboplatin].

Platinum compounds primarily act by damaging cellular targets inducing direct or indirect DNA alterations, and cytoplasmic proteins modifications. Molecular and cellular mechanisms of platinum resistance include increase of DNA repair, amplification of detoxifying proteins, modification of platinum transport, and alteration of oncogenes expression. This overview will describe those preclinical constatations related to cisplatin and will focus on carboplatin specificity.

Antineoplastic Agents↗
PubMed2000

[Chemotherapy of non-small cell lung cancer: non-cisplatin based combinations].

The rationale for the association of two cytotoxic agents is based on obtaining the best possible synergy with the lowest level of interactive toxicity. The original mechanism of action of gemcitabine makes this drug a logical choice in the treatment of non-small cell lung cancer (NSSLC). Numerous phase I and phase II studies assessing the use of gemcitabine-based combinations in NSSLC are currently underway. These associations without cisplatin will quite naturally be positioned as second line therapy for NSSLC. The high response rates, however, also make these combinations particularly interesting candidates for first-line therapy, and they are shortly to be compared in phase II trials with traditional cisplatin-based treatment regimens. Protocols using cisplatin-based associations already have proven efficacy, but the same is expected to apply to other protocols without cisplatin, particularly those using innovative drugs such as gemcitabine, vinorelbine and taxanes. The different studies already concluded, or those currently underway, therefore constitute a basis for developing sequential treatment strategies in NSSLC. Gemcitabine is one of the new tools available to practitioners to improve patient prognosis in terms of clinical benefits and improved survival.

Antimetabolites, Antineoplastic↗
PubMed1999

Docetaxel-cisplatin combination (DC) chemotherapy in patients with anthracycline-resistant advanced breast cancer.

PURPOSE: The safety and efficacy of a docetaxel-cisplatin combination (DC) were evaluated in 41 patients pretreated for advanced breast cancer (ABC). PATIENTS AND METHODS: The first 2 patients received 85 mg/m2 docetaxel followed, 6 hours later, by 80 mg/m2 cisplatin repeated every 3 weeks; the other 39 received the same regimen, with 75 mg/m2 docetaxel. Appropriate dose reductions but no growth factor administration were planned. Treatment was continued until disease progression, excessive toxicity or patient refusal. RESULTS: A total of 223 chemotherapy courses were administered, with a median of 6 cycles per patient (range 1-8). All 41 patients were assessed for toxicity using NCI-CTC. Severe neutropenia was experienced by 38 patients (93%) (11 at grade 3, 27 at grade 4, 10 with febrile neutropenia). There was one death due to neutropenic septic shock. Grade 3 thrombocytopenia occurred in three patients (7%). Five patients (12%) had grade 2 neurosensory toxicity, two (5%) experiencing partial hearing loss. Grade 3 fluid retention occurred in three patients (7%). Of 38 anthracycline-resistant patients, 33 were evaluable for response. Two had a complete response (CR) and ten a partial response (PR), giving an objective response rate of 36%, (95% CI: 20%-55%). Stable disease (SD) was observed in 14 patients (42%), 7 (21%) had progressive disease (PD). Among the three non-resistant patients, two PRs and one SD were observed. Median duration of response was 29 weeks (range 18-70), median time to progression 21 weeks (4-70), and median overall survival 50 weeks (4-104+). CONCLUSIONS: This DC regimen is active, with an acceptable safety profile in anthracycline-resistant ABC patients. Its place as a second-line treatment alternative to docetaxel alone or to other second-line combination regimens remains to be determined.

Adult↗
PubMed1998

Selective killing of glioma cell lines using an astrocyte-specific expression of the herpes simplex virus-thymidine kinase gene.

Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This can be accomplished by use of the promoter of the glial fibrillary acidic protein gene, an intermediate filament protein expressed primarily in astrocytes. A plasmid containing the HSV-TK gene, driven by the human glial fibrillary acidic protein promoter gfa2, was lipofected into glioma cell lines and into an ovarian cancer cell line. Treatment with ganciclovir showed efficient killing of glioma cells, with no effect on the ovarian cells. Thus, the gfa2 promoter is a promising candidate for directing expression of toxic genes to gliomas.

Astrocytes↗
PubMed1998

Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma.

BACKGROUND: Serum neuron specific enolase (NSE) is the most sensitive tumor marker of small cell lung carcinoma (SCLC) at diagnosis. Its prognostic value is still debated. Thus, the authors decided to assess the predictive value, in terms of complete response and survival, of serum NSE measured before and after one cycle of chemotherapy in patients with SCLC. METHODS: Sera from 135 patients with histologically proven limited (n = 63) or metastatic (n = 72) SCLC were obtained. Clinical and biologic parameters with a known or suspected prognostic relevance were reviewed. Serum NSE was measured before chemotherapy (D1-NSE) and 28 days after its initiation (D28-NSE). The prognostic value of the parameters under study was evaluated in univariate and multivariate analyses using the Cox proportional hazards model and logistic regression analysis. RESULTS: The level of serum NSE was raised in 120 patients (88%) prior to therapy. The probability of a normal D28-NSE value was not affected by the baseline D1-NSE value. Disease extension (P = 0.0005), performance status (P = 0.0001), D28-NSE (P = 0.003), and carcinoembryonic antigen (CEA) levels (P = 0.008) were found to be predictive for survival, whereas age, gender, plasma sodium, serum protides, and D1-NSE were not. Median survival and 2-year overall survival were 15.3 months and 21% (95% confidence interval [CI], 13-31%) when D28-NSE was normal and 8.1 months and 15% (95% CI, 8-27%) when it was not (P < 0.03). Only performance status (P = 0.001), disease extension (P = 0.002), and D28-NSE (P = 0.02) were found to be independent prognostic parameters for survival in the multivariate analysis. A simple prognostic index was developed using these 3 variables. Limited disease, a normal D28-NSE value, and a normal CEA value prior to therapy were the only parameters predictive for complete response in the univariate analysis, and D28-NSE (P = 0.01) and disease extension (P = 0.0001) were found to be independent variables in multivariate analysis. A complete response to therapy occurred in 62% with a normal D28-NSE value and in only 34% in the opposite case. CONCLUSIONS: Normal serum D28-NSE is a strong, independent early predictor of both complete response to therapy and survival. This simple tool may be proposed for use in the clinic and in research, in association with an assessment of disease extension and performance status, to predict the outcome of patients with SCLC.

Adult↗
PubMed1998

Initial management of primary mediastinal seminoma: radiotherapy or cisplatin-based chemotherapy?

Primary mediastinal seminoma is an uncommon neoplasm, the optimal management of which is still debated. Radiotherapy produces a 65% disease-free survival rate. We assess whether these results have been improved with the advent of cisplatin-based chemotherapy. Data from 14 patients treated at the Institut Gustave-Roussy were reviewed. 9 had received cisplatin-based chemotherapy (Group 1): their outcome was compared with that of 5 patients treated with radiotherapy without chemotherapy (Group 2). We also reviewed data from the English literature using strict criteria, and report results concerning patients who received cisplatin-based chemotherapy and those who received radiotherapy. 8 of the 9 patients (89%) in Group 1 are long-term disease-free survivors and only 3 of 5 patients in Group 2. The patient who died in Group 1 was the only one who refused surgical resection of residual masses after chemotherapy. The review of the literature revealed that 59 of 68 (87%) patients initially managed with cisplatin- or carboplatin-based chemotherapy and for whom sufficient data are available, are long-term survivors and free of disease. Some of these patients had also received radiotherapy. Only 64 of 103 (62%) treated with thoracic radiotherapy without chemotherapy were long-term disease-free survivors. The disease-free survival rate of 51 patients who received cisplatin-based chemotherapy (excluding those who received carboplatin) was 86%. The difference in survival between patients administered cisplatin-based chemotherapy and those who underwent radiotherapy is apparently not due to unbalanced prognostic factors, the effect of time or non-specific medical management. We conclude that cisplatin-based chemotherapy allows long-term disease-free survival in approximately 85% of patients. These results seem to be higher than those obtained without cisplatin-based chemotherapy. However, a randomised study is required for definitive conclusions, but it is very unlikely that such a study will be performed due to the rarity of this neoplasm. Another alternative would be a meta-analysis based on individual data.

Adult↗
PubMed1998

Review article: Overview of medical treatments in unresectable hepatocellular carcinoma--an impossible meta-analysis?

BACKGROUND: Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist. AIM: To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials. METHODS: Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen. RESULTS: Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference -3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference -2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1-18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = 0.9-6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0-49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant. CONCLUSIONS: No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

Administration, Cutaneous↗
PubMed1997

Ca125 and neuron-specific enolase (NSE) as tumour markers for intra-abdominal desmoplastic small round-cell tumours.

Seven consecutive patients with intra-abdominal desmoplastic small round-cell tumours were screened at presentation for carcinoembryonic antigen (CEA), Ca19-9, Ca15-3, Ca125, alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and neuron-specific enolase (NSE). Initially elevated tumour markers were used to monitor therapy and follow-up. Tumour marker assays were all in the normal range, with the exception of Ca125 and NSE. The Ca125 level was initially high in six of the seven patients (86%) with a median value of 200 U ml-1 and a range of 22-735 U ml-1. The NSE value was elevated before therapy in three of the five patients (60%) for whom assay results were available, with a median of 19 ng ml-1 and a range of 6.8-37.5 ng ml-1 . Ca1 25 normalized in five out of six cases and NSE always normalized during chemotherapy, but neither of these two tumour markers correlated specifically with response, as only one patient experienced a partial response, five tumour stabilization and the remaining patient tumour progression. At progression, Ca125 was again elevated in two out of four cases several weeks before clinical relapse and NSE in only one out of three cases. Ca125 and NSE are frequently raised in the serum of patients with intra-abdominal desmoplastic small round-cell tumours before therapy, but are not reliable monitors of the course of the disease. However, normalization is frequently associated with an improvement of symptoms or a moderate clinical response.

Adolescent↗
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

[Telomeres, telomerase and cancer].

The chromosome ends are specialized nucleoprotein structures called telomeres, which length predicts replicative capacity of cells. Activation of telomerase, the DNA polymerase that synthesizes telomeric repeats, seems to be necessary for cells to become immortal. Methods of measuring telomerase activity, now reliable and semiquantitative, have shown that telomerase is expressed in most human cancers, but not in normal somatic tissues. Research about regulation of telomere length and telomerase activity, highlights connexions between senescence and cancer. This article details diagnosis, prognosis and therapeutic prospects linked to the study of telomerase activity.

Animals↗
PubMed1996

Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's Anticancer Drug Screen panel.

The present study was designed to explore the activity of platinum compounds in cisplatin-resistant cell lines, the unselected cell lines of the National Cancer Institute's Anticancer Drug Screen, and the potential for use in combination. The activities of four platinum compounds in cisplatin-resistant KB and A2780 cells were investigated. The cells were highly resistant to cisplatin and cross-resistant to carboplatin, but less than one-tenth as resistant to oxaliplatin and tetraplatin. Cellular accumulation of all platinum compounds was decreased in both resistant cell lines. When the activities of cisplatin and oxaliplatin were evaluated in the National Cancer Institute's Anticancer Drug Screen, marked differences were observed. Evaluation of the activity profile using the COMPARE program revealed a different pattern for both agents: the cisplatin activity profile was similar to those of other diamine-platinum compounds, alkylating agents including melphalan, and camptothecin analogs, whereas the activity profile of oxaliplatin resembled those of other "dach" (diaminocyclohexane) platinum compounds and of acridine derivatives. The sensitivity profiles are influenced by the target(s)/mechanism(s) of action and the mechanism(s) of resistance of a drug. The dissimilarity in profiles suggests that these two platinum compounds have a different target(s)/mechanism(s) of action, a different mechanism(s) of resistance, or most likely both. Studies evaluating combinations of cisplatin/oxaliplatin suggest that the activities of these two agents are at least additive and possibly synergistic. Oxaliplatin has a different spectrum of activity and low cross-resistance to cisplatin and should be valuable in cisplatin refractory patients or in combination with cisplatin.

Antineoplastic Agents↗
PubMed1996

CPT-11. The European experience.

CPT-11 is a derivative of camptothecin, which has a broad spectrum of antitumor activity, both in vitro and in vivo. Like camptothecin, CPT-11 is a selective inhibitor of the DNA enzyme topoisomerase I. Phase I trials were conducted in Europe with the aim of determining the recommended CPT-11 dose and schedule for evaluation in phase II trials. The phase I trials assessed the toxicity of CPT-11 in 235 patients and tested three different administration schedules. CPT-11 was administered as a single infusion once every three weeks, as a weekly infusion for three weeks out of every four, and as a daily infusion for three consecutive days every three weeks. The maximum tolerated dose (MTD) was 115 mg/m2 in the daily schedule and 145 mg/m2 in the weekly schedule. When the drug was administered once every three weeks, diarrhea became the dose-limiting toxicity at doses above 350 mg/m2. This schedule allowed the highest dose intensity to be obtained, was the best tolerated, and allowed ambulant treatment. Finally, using this schedule, a combination of CPT-11 with high doses of loperamide allowed the dose of CPT-11 to be increased to 750 mg/m2. An ongoing phase I trial is investigating the combination of CPT-11 and 5-fluorouracil (5-FU) in various solid tumors. Although the MTD has not yet been reached, preliminary results have not demonstrated any pharmacokinetic interaction between the two drugs, contrary to the findings of a previous Japanese study. Based on the results of the three phase I trials, CPT-11 administered at a dose of 350 mg/m2 as an intravenous infusion over 30 minutes once every three weeks has been recommended for assessment in phase II trials. The phase II trials started in Europe at the beginning of 1992. To date, CPT-11 has showed remarkable efficacy in colorectal cancer, even in patients resistant to 5-FU. Interesting results have also been obtained in pancreatic, cervical and lung cancer. Future trials will make it possible to assess whether there is a place for CPT-11 in combination with other cytotoxic agents or radiotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed1996

[Resistance to anticancer drugs].

Due to inefficacy of chemotherapy in several cancers, chemoresistance mechanisms which are intrinsic to tumor cells have been extensively described in human cancer cell lines. Detoxifying mechanisms including active efflux pumps (P-gp, MRP or LRP) and/or drug inactivation (glutathione) as well as increased DNA repair have been identified and demonstrated to be involved in chemoresistance processes. Moreover expression of genes implicated in proliferation, differentiation or apoptosis functions has been shown to indicate drug response. Several mechanisms very often coexist within the tumor cell: it is possible even that detoxifying mechanisms are dependent on oncogenes and suppressor genes regulating proliferation, differentiation and/or apoptosis. In human tumor specimens, some of these mechanisms are regularly found and thus lead to develop strategies to block them. In that respect, the first example is the development of modulators of P-gP, a membrane efflux protein, which constitutes the archetype of detoxifying drug mechanisms. In spite of technical difficulties encountered to properly identify and quantify expressions of these biomarkers, ongoing research in cancer chemotherapy now largely relies on chemoresistance mechanisms.

DNA Repair↗
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

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↗