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Biomedical subjects

M Clavel

Publications and source records attributed to M Clavel.

At least 55 records · Page 3Linked to original sources
PubMed1993

Multivariate analysis of prognostic factors in patients with non HIV-related primary cerebral lymphoma. A proposal for a prognostic scoring.

Between 1982 and 1991, 41 patients were treated for non HIV related primary cerebral lymphoma (PCL) in our institute. The purpose of this study was to perform a multivariate analysis of prognostic factors for survival in these patients. The presence of a CSF protein level over 0.6 g l-1 at diagnosis was found to be the most significant unfavourable prognostic factor in univariate analysis and had not previously been reported. Among the five significant prognostic factors at diagnosis, (age over 60 years, performance status--ECOG scale--over 2, memory dysfunction, non hemispheric tumour site, CSF protein level over 0.6 g l-1 at the diagnosis), three independent factors were identified in multivariate analysis: (1) CSF protein level (P = 0.007; RR = 4.7); (2) PS > 2 (P = 0.04, RR = 2.65); (3) age over 60 (P = 0.08; RR = 2.43). Using the regression coefficient of these three parameters, we determined a prognostic index which allowed us to distinguish three risk groups whose theoretical median survival is 4, 20 and 54, months respectively in patients with non HIV related PCL. These results indicate that PCL is an heterogeneous disease in terms of the prognostic in which three subgroups with discriminant survival can be identified.

Adolescent↗
PubMed1993

Randomized phase II trial of iproplatin and carboplatin in advanced breast cancer. The EORTC Early Clinical Trials Group and the EORTC Data Center.

BACKGROUND: The observed activity of cisplatin in breast cancer and its unattractive toxicity profile in palliative treatment warranted further study of platinum analogues in this disease. PATIENTS AND METHODS: Sixty-two patients with recurrent or metastatic breast cancer, 61 of whom had been previously treated with chemotherapy, were randomly assigned to therapy with either iproplatin (n = 32) or carboplatin (n = 30). Both platinum analogues were administered intravenously, iproplatin at a dose of 240 mg/m2 every 4 weeks and carboplatin at a dose of 450 mg/m2 every 5 weeks. RESULTS: Only two patients responded to iproplatin (7%) for durations of 21 and 61 weeks, and one patient responded to carboplatin (3%) for a duration of 64 weeks. All responses were complete. At the given dose schedules carboplatin was more myelosuppressive than iproplatin. Non-hematologic toxicities included nausea and vomiting (93% vs. 90%), diarrhea (20% vs. 10%) and hemorrhage (16% vs. 10%) for iproplatin and carboplatin, respectively. Two patients developed alopecia with carboplatin. No renal toxicity was observed. CONCLUSIONS: Both iproplatin and carboplatin have limited activity in previously treated women with advanced breast cancer when given in conventional dosages.

Adult↗
PubMed1993

Epirubicin in patients with advanced or recurrent adenoid cystic carcinoma of the head and neck: a phase II study of the EORTC Head and Neck Cancer Cooperative Group.

BACKGROUND: Because of the rarity of salivary gland cancer, little is known about the single-agent activity of most anticancer agents in the different histologic types of these cancers. PATIENTS AND METHODS: Twenty patients with advanced or recurrent adenoid cystic carcinoma of the head and neck were treated with epirubicin on a low-dose weekly schedule (30 mg/m2/week) for eight weeks and, in instances of no response, a high-dose three-weekly schedule (> or = 90 mg/m2). Thirteen patients had locoregional disease (12 recurrences), seven of them also had distant metastases and seven had distant metastases only. All had documented progressive disease, and 17 were symptomatic. RESULTS: Two objective responses of 7.5 and 20 months were observed in patients with locally recurrent disease, and ten patients showed disease stabilization. The median time to progression was 16 weeks (range 2-250 weeks) and the median survival 67 weeks (range 13-272+ weeks), with three patients still alive more than five years after the initiation of chemotherapy. Contrary to the rather modest objective response rate, symptomatic improvement occurred more frequently (29.4%) and was evident within 8 weeks of treatment. CONCLUSIONS: This type of chemotherapy should be reserved for patients with rapidly progressive disease or those with symptomatic disease.

Adult↗
PubMed1993

Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS: One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS: Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION: This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.

Adult↗
PubMed1993

The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group.

We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.

Adult↗
PubMed1993

[Immunotherapy of metastatic kidney cancer].

Interleukin 2 (IL2), like Interferon alpha (IFN), is active in metastatic renal cancer, considered to be a chemoresistant cancer. 20 to 30% of objective responses, including 5 to 10% of complete remissions are reported with various protocols of IL2 administration. The considerable toxicity is now well controlled, allowing treatments to be administered in standard wards or even on an outpatient basis by subcutaneous injection. IFN, generally given as long-term treatment, achieved average response rates of between 15 and 20%. Although IL2 and IFN have been granted Product Marketing Authorization in France, the modalities of optimal administration, the place of the combination of IL2-Interferon alpha and the factors predictive of response to treatment still remain unclear.

Humans↗
PubMed1992

Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian adenocarcinoma.

Pharmacokinetically guided administration of melphalan was investigated during a pilot study in patients with advanced ovarian adenocarcinoma. The schedule involved a fixed dose on day 1 (7.9 mg) followed by a second dose on day 2, calculated on the basis of pharmacokinetic data to achieve a target area under the concentration-time curve (AUC). 20 courses of intravenous melphalan were administered to 7 patients. AUC, standardised to 1 mg/m2, ranged between 4.3 and 8.9 (mg/l) min. In 12 fully evaluable courses, less than 15% deviation from the target AUC was found, showing that AUC monitoring was possible by means of the test dose. Pharmacodynamic effects showed a positive correlation with melphalan AUC. Myelosuppression appeared at 47 (mg/l) min and grade 3 or 4 haematological toxicities were observed in 4 cycles, associated with AUC values ranging between 86 and 112 (mg/l) min. Relative leucocyte decreases were well correlated with AUC values.

Adenocarcinoma↗
PubMed1992

An image cytometric DNA-analysis in breast neoplasms. Parameters of DNA-aneuploidy and their relationship with conventional prognostic factors.

In this prospective study, an image cytometric DNA-analysis was performed in 86 women with breast neoplasms (72 primary invasive carcinomas and 14 benign lesions). Four DNA ploidy parameters were analysed: histogram type (according to AUER classification), DNA-index, tumor cells with DNA content above the 5n limit and DNA malignancy grade (DNA-MG, calculation according to Böcking). Their correlations with well established prognostic factors in breast carcinomas (tumor size, lymph node status, histologic grade, hormone receptor content) were studied. All but one benign lesions were diploid (13/14 cases), whereas the majority of the primary invasive breast carcinomas were aneuploid (58/72 cases). A predominance of carcinomas with a percentage of cells superior or equal to 1% with DNA content above the 5n limit was observed (54 cases out of 58). Most of the aneuploid tumors had a histogram type III or IV (53 cases) or a high DNA-index (50 cases). Of these 58 aneuploid cases, only 26 tumors had a DNA-MG superior to 1. Interestingly, 26 tumors had the 4 criteria of aneuploidy, 19 had 3 and 9 had 2 and only 4 tumors had one parameter. The DNA-MG was significantly related to hormonal receptors (p less than 0.001) and tumor size (p less than 0.01). The histogram types (Auer classification) and the DNA content above the 5n limit were correlated with histologic grade (SBR or SBRM) (p less than 0.02). Concerning the DNA-index no correlation was observed with well established prognostic factors. On the other hand no significant correlation was found between these new biologic variables and lymph node status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma.

The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion of IL2 at a dose of 18 x 10(6) iu m-2 d-1 for 2 periods of 5 days separated by a 6 day break. Toxicity was not different compared with younger patients (e.g. fever, hypotension, rise in creatinine level), except for cardiac toxicity which was of great concern. Despite normal cardiac tests prior to inclusion into the study, abnormalities of the cardiac rhythm ranging from tachycardia to ventricular extrasystoles occurred in 44% of the patients and IL2 cardiac toxicity was responsible for one toxic death. Three objective responses, i.e. one partial and two complete persistent responses, were seen in 22 evaluable patients. Thus, if age does not seem to modify the potential for response to IL2 therapy, cardiac toxicity appears as a limiting factor for intravenous schedules of IL2.

Aged↗
PubMed1992

A phase II trial of 10-ethyl-10-deaza-aminopterin, a novel antifolate, in patients with advanced and/or recurrent squamous cell carcinoma of the head and neck. The EORTC Head and Neck Cancer Cooperative Group.

Forty-seven patients with advanced and/or recurrent squamous cell carcinoma of the head and neck were treated with 10-ethyl-10-deaza-aminopterin (10-EdAM), a new analogue of methotrexate. The drug was given as a weekly i.v. bolus injection, starting at 80 mg/m2 with two dose increments of 10% if no toxicity was observed after two weeks. Only patients with tumors of the larynx, oral cavity, oropharynx and hypopharynx were included in the trial. Eighty-two percent of the patients had had prior surgery and/or radiotherapy. Forty-four patients were evaluable for response and toxicity. Five CR (12%) and five PR were obtained, yielding a response rate of 24% (CR+PR). The toxicity was similar to that usually seen with methotrexate; stomatitis and skin toxicity were rather pronounced. The data suggest that 10-EdAM has activity similar to that of methotrexate in patients with head and neck cancer.

Adult↗
PubMed1992

Phase II trials of fosquidone (GR63178A) in carcinoma of the breast, head and neck, ovary and melanoma.

A total of 91 eligible patients with metastatic cancer have been treated in a series of phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were breast (24), ovary (25), head and neck (21) and melanoma (21). All patients, except those with melanoma had received prior chemotherapy. The drug was given intravenously as a 20 min infusion, at the dose of 120 mg/m2 on days 1 to 5 of a 3 week cycle. Treatment was well tolerated; the only significant side-effects being mild headaches and generalised musculo-skeletal pains. Response was assessed after 2 cycles of therapy. Only one patient (with head and neck cancer) achieved an objective partial response, lasting 6 weeks. A total of 12 patients demonstrated stable disease for a median duration of 15 to 20 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.

Adult↗
PubMed1992

Value of early pharmacodynamic and pharmacokinetic investigations with anticancer drugs: data from phase I tolerance studies on a new vinca alkaloid derivative.

1. A novel anticancer vinca alkaloid derivative (I) has been given as an i.v. bolus to cancer patients, using four different dosage regimens with dose levels ranging from 0.04 to 0.84 mg/m2 (equivalent to between 0.12 and 1.35 mg per dose), and the pharmacokinetics determined up to 72 h after dosing. In addition, secondary effects of leukopenia and neutropenia, were related to drug exposure using a sigmoid Emax model. 2. Plasma levels of I declined in a triphasic manner with a terminal half-life of approximately 50 h; most drug elimination (55%) being associated with the terminal phase. 3. Clearance of I was relatively low (245 +/- 160 ml/min) and remained constant with increasing doses. Initial distribution volume was low (approximately 71) but once distribution was complete, it was comparatively high (327 +/- 2121). 4. Both leukopenia and neutropenia were fitted successfully to a sigmoid Emax model showing that these effects were related to the total exposure to the drug. The Hill constant was less than 1, indicating a relatively shallow exposure/response curve and a predictable, graded increase in response with increasing I exposure, rather than a sudden quantal response. 5. Pharmacokinetically, I shows some similarities to other vinca alkaloids in its plasma level decline profile, although there are some notable differences which can be exploited clinically. In addition, the ability to model both leukopenia and neutropenia to the exposure to I, provides a valuable tool in the design of the most appropriate dosage regimen for the drug, as well as for dose adjustment taking into account inter-individual variations.

Adolescent↗
PubMed1992

High dose chemotherapy with ABMT in soft tissue sarcomas: a report of 22 cases.

Twenty-two patients with locally advanced or metastatic soft tissue sarcomas received high dose chemotherapy with autologous bone marrow graft. Eleven patients receiving melphalan also received fractionated total body irradiation. Six patients (four in CR and two in PR) were intensified after first line therapy. Thirteen patients were grafted after chemosensitive relapse: seven in second CR, one in third CR, one in first PR, three in second PR and one in fourth PR. Three patients with primary refractory disease were intensified. The overall response rate in 66% in nine evaluable patients. The overall median survival and disease-free survival were 19 and 15 months, respectively. The actuarial survival rates at 2 and 5 years were 40% and 32% respectively. There was one treatment-related death due to infection. We conclude that high dose chemotherapy is feasible and provides reasonable response rates in patients with advanced soft tissue sarcomas.

Adolescent↗
PubMed1991

Doxorubicin plus ifosfamide with rhGM-CSF in the treatment of advanced adult soft-tissue sarcomas: preliminary results of a phase II study from the EORTC Soft-Tissue and Bone Sarcoma Group.

Doxorubicin and ifosfamide are the two most active agents used in the treatment of advanced inoperable soft-tissue sarcoma, but their use in combination produces dose-limiting myelosuppression. To explore the feasibility of combining optimal doses of both drugs, doxorubicin (75 mg/m2) and ifosfamide (5 g/m2) were given every 3 weeks with recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF; 250 micrograms m-2 day-1) by subcutaneous injection for up to 14 days after each course. A total of 52 patients with progressive metastatic soft-tissue sarcoma were entered, none having received prior chemotherapy. One patient was ineligible and received no treatment after registration. Preliminary analysis of six cycles of chemotherapy revealed that the full protocol dose intensity had been administered to the majority of patients. Although the median leucocyte and neutrophil counts did not fall with subsequent courses of chemotherapy, the duration of neutropenia increased with each course delivered. Cumulative thrombocytopenia was a major dose-limiting toxicity and was the main reason for any dose modifications that occurred. Although 26 patients experienced infections after one or more courses of treatment, in only 7 was admission required for parenteral antibiotics. One patient died as a result of septicaemia after the first cycle of treatment. To date, there have been 22 responses (43%) with 8% complete remissions. It appears that the administration of rhGM-CSF allows this high-dose regime of chemotherapy to be given safely and the early encouraging response rate adds support to the concept that increasing the dose of doxorubicin improves the outlook for patients with advanced soft-tissue sarcomas.

Adult↗