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Biomedical subjects

C Borel

Publications and source records attributed to C Borel.

At least 55 records · Page 3Linked to original sources
PubMed1996

Endogenous interleukin 6 levels in patients with metastatic malignant melanoma: correlation with tumor burden.

The involvement of interleukin (IL-) 6 in malignant disease has been investigated in a variety of different malignancies. To evaluate whether serum IL-6 is a useful disease marker in metastatic malignant melanoma (MMM), we studied the time course of endogenous IL-6 secretion in 41 patients treated with cisplatinum, IL-2, and IFN-alpha. Furthermore, the relationship of endogenous IL-6 concentrations to the tumor burden and/or the clinical response was also evaluated. The baseline serum IL-6 levels were significantly higher in patients with MMM than in the control group (P = 0.002). When tumor burden was taken into consideration, we found that IL-6 levels were higher in patients with high tumor burden than in patients with low tumor burden. During treatment in the whole patient population, a higher serum IL-6 level was observed in nonresponding as compared to responding patients at days 7 (P = 0.0005), 21 (P = 0.002), and 35 (P = 0.009). The follow-up of serum IL-6 in patients with MMM according to the tumor burden and clinical response demonstrated that: (a) IL-6 levels were significantly higher at days 7 and 21 in patients with high tumor burden as compared to those with low tumor burden; and (b) IL-6 levels remain significantly higher in nonresponding patients as compared to responding patients regardless of the tumor burden. From these results, we can conclude that endogenous IL-6 may play a role in the failure of IL-2 therapy in such patients, since the very early IL-6 increase is correlated with the tumor mass and nonresponse to biochemotherapy. Therefore, it seems that the early detection of endogenous IL-6 may represent valuable information for monitoring the response to biochemotherapy in patients with MMM.

Adult↗
PubMed1995

A phase II study of tamoxifen combined with cisplatin-interleukin 2 and alpha-interferon in metastatic melanoma.

Tamoxifen (TAM) has been reported to enhance cisplatin (CDDP) cytotoxicity in experimental and clinical melanoma studies. Based on our previous experience with sequential cisplatin-interleukin-2 (IL2)-interferon (IFN), we performed a phase II study of TAM combined with our original CDDP-IL2-IFN regimen in 22 pretreated metastatic melanoma patients. With a 41% response rate (95% CI, 21-61) we confirmed the interesting antitumor activity of CDDP-IL2-IFN combination; however, TAM enhanced neither the response rate nor the duration of response, but appeared to induce significantly more myelotoxicity, as compared to our previous results with CDDP-IL2-IFN alone. Whereas mechanisms by which TAM may modulate CDDP cytotoxicity in melanoma tumors remain unknown, the exact place of TAM, if any, and its safety in chemotherapeutic or chemoimmunotherapeutic combinations require further investigations.

Adult↗
PubMed1995

Fotemustine, dacarbazine, vindesine combination chemotherapy in advanced malignant melanoma: a phase II study of 43 patients.

Fotemustine and dacarbazine constitute the most active single chemotherapeutic agents in the treatment of melanoma. In this phase II study we evaluated the activity and toxicity of a combination of fotemustine, dacarbazine and vindesine as a means of increasing response rate and survival time. Between September 1989 and November 1993, 43 patients with advanced melanoma were treated with a combination of 100 mg/m2 fotemustine on days 1 and 8, 250 mg/m2 dacarbazine on days 15 and 16 and 2 mg/m2 vindesine on days 15 and 16 as induction treatment. After a 5-week rest period, the patients exhibiting a response or stable disease received the same drugs administered once every 28 days as maintenance therapy until either progression or toxicity was observed. Among 41 evaluable patients, there were six complete responses and eight partial responses. The overall response rate was 32% (95% confidence interval: 18-46%), with 8 months median duration of response. Median survival time was 10 months. This regimen was well tolerated. From this large phase II study, we conclude that such a combination is active against advanced malignant melanoma and seems to be more effective than fotemustine or dacarbazine used alone, especially on visceral metastatic sites.

Adult↗
PubMed1995

[Role of radiotherapy in the treatment of meningioma].

Between 1962 and 1986, 32 patients with intracranial meningiomas were referred to the Institut Gustave-Roussy for external radiotherapy either after incomplete surgery, or unfavorable histology (meningiosarcoma/anaplastic meningioma), or after recurrences. In the latter case, the mean time interval between the first surgery and the recurrence was 2 years (range: 1-6 years). Radiotherapy was performed using photons, electrons or mixed photons-electrons. The mean total dose was 48 Gy (range: 9-65 Gy) delivered in a mean time of 35 days with a 19 mean number of fractions. Radiotherapy was interrupted in three cases at 9 Gy-17 Gy-20 Gy because of neurological worsening. The actuarial 5-year survival was 64%. Among the 32 patients, 11 died, eight of tumoral progression or recurrence and three of other causes (one ovarian carcinoma, two unknown). Among the 21 alive patients, eight presented a recurrence; five of them could be reoperated on with two complete resections. None of the following factors were found to be of prognostic value on the survival nor on the recurrence occurrence: age, tumor location, first surgical resection type, and, in the group of patients treated at the time of recurrence, the quality of the surgery at the time of recurrence and the time interval between the first surgery and the recurrence. Only one factor was evidenced as of significant value on the recurrence as well as the 10-year survival: the total dose of irradiation with a 10-year survival rate of 74% for total doses higher than or equal to 47 Gy versus 14% when the total dose was lower than 47 Gy.

Adult↗
PubMed1994

Follow up of soluble IL-2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy.

Immunological parameters following chemoimmunotherapy combination were studied in 31 patients with metastatic malignant melanoma. They received Cisplatin (100 mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN-alpha; Roche) was given subcutaneously three times weekly. No significant change in CD4/CD8 ratio at onset or during treatment was observed between responder (n = 19) and non-responder (n = 12) patients. Regarding the IL-2 receptor (IL-2R) study, the percentage of cells expressing Tac (p55) receptor did not change either for healthy volunteers (n = 20) and patients before any therapy, or between responder and non-responder patients. Concerning serum soluble IL-2R shedding before therapy, we observed a significant increase (P = 0.001) in patients (79 +/- 40 pM) compared with healthy donors (30 +/- 15 pM), but no significant variation was seen between responder and non-responder patients. In contrast, during the treatment, the soluble IL-2R level increased in both groups but, interestingly, a significant difference was found between responder and non-responder patients from day 7 (P < 0.05) to day 21 (P < or = 0.01), suggesting that the cells from non-responder may be slower in becoming stimulated. This finding is the most striking point of our study and suggests that sIL-2R might be an early predictive factor of the clinical response as obtained by logistic regression (P = 0.0063). Therefore patients with a serum soluble IL-2R level greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical response.

Adult↗
PubMed1993

Chemoimmunotherapy of metastatic malignant melanoma. The Salpétrière Hospital (SOMPS) experience.

Optimistic results were obtained in the treatment of 39 patients with surgically incurable metastatic malignant melanoma using a regimen including 2 to 3 monthly induction cycles of cis-diamminedichloroplatinum (CDDP), recombinant interleukin-2 (rIL-2) and interferon alpha-2a (IFN alpha-2a). 33 of 39 patients were pretreated with chemotherapy (dacarbazine and/or fotemustine:31, CDDP:6) and 17 of 39 with IFN alpha-2a. Overall response rate was 54% with 13% achieving a complete response for up to 59+ weeks. Moderate to severe side-effects were reversible on rIL-2 cessation and toxicity was manageable in a routine inpatient setting. These results are especially encouraging as they were seen in previously treated patients, classically low responders, including 3 who were resistant to cisplatin or other platinum complexes. The question remains if this regimen bypasses traditional mechanisms of drug resistance.

Adult↗
PubMed1993

Dicranin, an antimicrobial and 15-lipoxygenase inhibitor from the moss Dicranum scoparium.

Extracts of nine mosses, collected in Switzerland, were screened for antimicrobial, antioxidative, and 15-lipoxygenase (15-lpo) inhibitory activities. The CH2Cl2 extract of Dicranum scoparium was found to possess pronounced antimicrobial activity against Bacillus cereus, Bacillus stearothermophilus, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. In addition, inhibition of soybean 15-lpo occurred at very low concentration. Phytochemical investigation of this extract afforded Z,Z,Z-octadeca-6-yne-9,12,15-trienoic acid [1] by a combination of chromatographic techniques. This compound, named dicranin [1], was found to be responsible for most of the biological activity. The strongest antimicrobial effect was observed against Streptococcus faecalis (disc diffusion assay). In contrast to the CH2Cl2 extract of D. scoparium, dicranin was inactive against E. coli. Dicranin was identified by ir, ms, and nmr spectroscopy. A 2D INADEQUATE experiment confirmed the structure and yielded the assignment of all 13C-nmr signals.

Anti-Bacterial Agents↗
PubMed1993

Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.

PURPOSE: To evaluate the activity and the toxicity of the combination of cisplatin (CDDP)/recombinant interleukin-2 (rIL-2) and interferon alfa-2a (IFN alpha) in disseminated malignant melanoma (DMM). PATIENTS AND METHODS: Between December 1990 and March 1992, 39 patients with biopsy-proven metastatic malignant melanoma (MM), bidimensionally measurable lesions and an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 entered this protocol. Seventy-nine percent had received previous chemotherapy including platinum complex (15%) and alpha interferon (44%). They received CDDP (100 mg/m2 on day 0) followed by IL-2 18.10(6) IU/m2/d continuous intravenous (IV) infusion from day 3 to day 6 and from day 17 to day 21. The cycle was repeated on day 28. Subcutaneous IFN alpha 9.10(6) IU three times weekly was administered throughout the treatment period. From day 66 or 94, patients were administered a maintenance cycle with CDDP 100 mg/m2, subcutaneous IL-2 5.10(6) IU/m2/d from day 15 to day 19 and from day 22 to day 26 and IFN alpha 9.10(6) IU three times weekly repeated every 5 weeks (maximum four cycles). RESULTS: Among 39 assessable patients, five patients achieved complete responses (CRs). Sixteen patients had partial responses (PRs). The overall objective response rate was 53.8%. The number of metastatic sites was the only response-predictive factor. Toxicity was manageable in a routine patient setting and there was no life-threatening toxicity. CONCLUSION: These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.

Adult↗
PubMed1993

Relapse in Guillain-Barré syndrome after treatment with human immune globulin.

Seven adult patients received human immune globulin intravenously as initial therapy for Guillain-Barré syndrome. Although all patients initially stabilized or improved, five patients deteriorated 1 to 16 days after completion of treatment. In all five patients, clinical worsening included loss of at least one functional grade together with a decreased forced vital capacity. We subsequently treated each patient with a course of plasma exchange, which led to varying degrees of clinical improvement in four. In contrast to previously reported relapse rates for Guillain-Barré syndrome, our experience suggests that clinically significant relapses may occur in patients more often following human immune globulin therapy than after either plasma exchange or no therapy.

Adolescent↗
PubMed1993

Alterations in natural anticoagulant levels during allogeneic bone marrow transplantation: a prospective study in 27 patients.

The natural anticoagulants (antithrombin III, protein C, protein S), plasminogen and tissue plasminogen activator antigen (t-PA ag), were measured in 27 consecutive patients following allogeneic BMT. Thrombosis and veno-occlusive disease were not seen in this study. Changes in the levels of these proteins occurred mainly during acute GVHD. There were 14 patients who had no acute GVHD (group I) and 13 patients who had acute GVHD (group II). No changes in antithrombin III (ATIII), protein C, protein S and t-PA levels were found in group II before the appearance of acute GVHD when compared with group I. However, we noted a significant rise in protein S (p = 0.01), antithrombin III (p = 0.001) and t-PA ag (p = 0.0004) levels during acute GVHD. In contrast, protein C levels decreased early in GVHD (p = 0.005), and then increased progressively over the course of a month post-GVHD. No changes in plasminogen levels were observed. These results might reflect activation of and/or damage to endothelial cells during GVHD.

Acute Disease↗
PubMed1992

[Treatment of primary cancer of the breast in elderly women. Role of hormone therapy].

About 40 percent of newly diagnosed breast cancers occur in women older than 65. Hormonotherapy plays an important role as adjuvant treatment of primary cancers in post-menopausal women because of their great hormone-dependence. The drug of choice is tamoxifen which is very well tolerated. Its beneficial effect appears to be related to the duration of administration. It also seems to be particularly promising in the initial treatment (neoadjuvant) of elderly women and potentially beneficial in the breast cancers said to be of good prognosis when the axillary nodes are not involved.

Aged↗
PubMed1992

Effects of 9, 12, 15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on platelet aggregation.

An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin) was extracted from Dicranum Scoparium and preincubated with platelets which were then stimulated by exogenous arachidonic acid (20:4 n-6). This molecule at 10(-4) M weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-5) M and with 10(-6) M of dicranin but to a lesser extent. Platelet hydroxylated dicranin metabolites were also found and the structure of the main compound determined by GC-MS was a 13-hydroxy derivative. Its origin has not yet been elucidated. Platelet aggregation induced by 1 microgram/ml of U46619, a structural PGH2 analogue was completely abolished in the presence of dicranin. Platelet aggregation induced either by thrombin or by arachidonic acid was inhibited by 10(-4) M of dicranin only after preincubation. This observation indicates that the formation of metabolites of dicranin are necessary to effect this inhibition. Dicranin is thus a new inhibitor of platelet aggregation and may prove to be useful for elucidating the effects of 12-HETE in biological systems.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Effects of 9,12,15-octadecatrien-6-ynoic acid on the metabolism of arachidonic acid in platelets and on the platelet aggregation.

An acetylenic fatty acid: 9,12,15-octadecatrien-6-ynoic acid (dicranin), extracted from Dicranum Scoparium was preincubated with platelets stimulated by exogenous arachidonic acid (20:4 n-6). Dicranin (10(-4) M) weakly inhibited the cyclooxygenase activity as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT) In contrast, the 12-hydroxy-eicosatetraenoic acid (12-HETE) synthesized by the 12-lipoxygenase was strongly increased by about 650%. The same effects were observed with 10(-6) M of dicranin but to a lesser extent. The main platelet hydroxylated dicranin metabolite determined by GC-MS was a 13-hydroxy derivative Platelet aggregation induced either by thrombin or by arachidonic acid or by U46619, an structural PGH2 analogue was inhibited by 10(-4) M of dicranin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Phase I study of Datelliptium chloride, hydrochloride given by 24-h continuous intravenous infusion.

Datelliptium chloride, hydrochloride (SR 95 156B, NSC 626718X, DHE) was studied in a phase I trial of escalating doses given on a single 24-h continuous intravenous infusion schedule. Doses were escalated from 40 to 500 mg/m2 in 19 patients who received a total of 24 courses. Courses were repeated after a minimal interval of 3 weeks. Local venous toxicity occurred at low doses (less than or equal to 100 mg/m2) and was circumvented by the use of a central venous access for higher doses. Other clinical adverse events occurred (greater than or equal to 330 mg/m2), including moderate nausea and vomiting, mild diarrhea, dry mouth, neuropsychiatric manifestations, and fatigue. All of these side effects were reversible and none was dose-limiting. The dose-limiting toxicity was related to hepatic laboratory-test abnormalities in the form of reversible elevations of levels of serum bilirubin and liver enzymes at doses of greater than or equal to 330 mg/m2. The maximum tolerated dose for this schedule is 500 mg/m2. Hematologic toxicity was minimal and non-dose-limiting. Neither drug-related deaths nor objective complete or partial responses were observed. However, a minor response and a long-term disease stabilization were obtained.

Adult↗
PubMed1992

[Primary chemotherapy in the treatment of breast cancer].

Between 1980 and 1992, 457 consecutive patients with initial breast cancer entered two successive protocols combining neoadjuvant chemotherapy, hormonotherapy (tamoxifen) and locoregional radiotherapy (teleradiotherapy and boost by iridium) as exclusive locoregional treatment. Cytological diagnosis, hormone receptors, cytological grading were provided by fine needle aspiration. Both protocols included velbe, thiotepa, methotrexate, 5FU and adriamycin with some minor differences regarding the schedule of doses and their number during induction and during the consolidation phase. In both studies, over 50% patients had locally advanced breast cancer (IIb, IIIa or IIIb). Chemotherapy induced tumor regression over 50% in 91% patients of the first protocol (30% complete clinical remission CR) and in 94% patients of the 2nd protocol (40% CR): in this protocol 20 poor responders were given a rescue protocol (2 CR; 9 partial remissions). The 5 year actuarial rate of breast preservation is 94% and the 5 year actuarial rate of local relapses is 15%. The cosmetic results according to Danoff are excellent 20%, good 55%, mean 35%. Disease free survival and overall survival compare favorably to published data: they depend on TNM stages, tumor differentiation and chemotherapy induced early tumor regression.

Adult↗
PubMed1991

Fotemustine (S 10036) in the intra-arterial treatment of liver metastasis from malignant melanoma. A phase II Study.

Fotemustine is a new nitrosourea which has shown some efficacy on disseminated malignant melanoma (DMM) (24.2% response rate (RR) among 153 patients in a Phase II trial) but little activity on hepatic metastasis (8.8% RR). In order to improve those poor results, hepatic intra-arterial infusion (HIAI) of fotemustine was performed. After two years, thirteen patients, all in good general condition, were evaluable. Seven were pretreated and six had extrahepatic metastasis on entry into the study. All patients had a surgically implanted intra-arterial catheter. The induction cycle consisted of 100 mg/m2/week for 3-4 weeks, followed by 5 weeks rest and maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Two complete responses (CR) (72+ and 145+ weeks) and six partial responses (PR) (7-18.5 weeks) were observed. The hepatic RR reached 61.5%. A RR of 42.8% was registered on preexisting EHM (one CR and one PR on cerebral lesions). Nevertheless, this treatment is limited by the high progression rate of 46.1% in extrahepatic disease. Toxicity was mainly hematologic (grade III-IV), comprising 36% neutropenia and 15% thrombopenia. Hepatic intra-arterial infusion of fotemustine is efficient therapy for liver metastases of DMM, but combination schedules (IV + HIA) are warranted.

Adult↗