PubMed Health⌕ Search

Biomedical subjects

T Dorval

Publications and source records attributed to T Dorval.

At least 73 records · Page 4Linked to original sources
PubMed1992

Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with melanoma and other metastatic cancers.

Thirty tumour specimens, among which were 17 melanomas, were cultured with recombinant interleukin-2 (IL-2) in order to produce tumour-infiltrating lymphocytes (TIL). In the melanomas, three categories of TIL were characterised. The first, containing mostly CD3+ and CD8+ cells, lysed only autologous tumour cells; the second, containing mostly CD3+ and CD4+ cells, lysed both autologous tumour cells and allogeneic cells lines; the third, with mixed phenotype although cytotoxic for K562 targets, did not kill melanoma cells. The optimal conditions for a good development of TIL were established: we found that the lymph node or cutaneous origin of the tumour was unimportant, a 2 h enzymatic treatment was optimum and that TIL grew well in AIM V serum free medium. Therefore the easiness and the reproducibility of the TIL cultures from melanoma tumour samples allows the rapid development of therapeutic trials in metastatic melanoma.

Adult↗
PubMed1992

IL-2 phase II trial in metastatic melanoma: analysis of clinical and immunological parameters.

Twenty-four patients with histologically proven metastatic malignant melanoma were included in a phase II trial of recombinant IL-2 (rIL-2, RU 49637). Twenty million international units (IU)/m2/day were given by continuous intravenous infusion on days 1 to 5, 15 to 18, and 29 to 31, and then monthly for 5 days until disease progression or major intolerance developed. All patients were evaluable for response and toxicity. Toxicity was consistent with one case of myocardial ischemia, 13 cases of grade III and IV hypotension, and 15 cases of proven sepsis. There were 8 objective responses: 4 of them were of short duration as they were observed on day 31 only. An activation of the immune system was detected in all patients. It was demonstrated by an increase in lymphocyte populations, especially in activated NK cells. A tendency for higher numbers of cytotoxic cells was found in patients with objective tumor responses. These results indicate a role for rIL-2 RU 49637 in treating patients with metastatic malignant melanoma. However, further trials are required to determine its optimal dosage and schedule of administration.

Adolescent↗
PubMed1992

[Treatment of metastatic malignant melanoma with interleukin-2].

Between April 1988 and December 1990, 37 patients with progressive histologically proven metastatic melanoma were treated with interleukin-2 according to three multicentric successive protocols. Eighteen males and 19 females entered the trial. Mean age was 44 years (range 20-66); none of the patients had severe visceral disease or brain metastasis. Superficial and visceral metastatic sites were equally distributed. Interleukin-2 was administered as a 3 to 5 day continuous intravenous infusion, at a dose varying from 16 to 24 million international units/m2/day, as previously described by West. The second course was given after a 9 to 16 day free interval and one to seven courses were administered (mean three courses). A total of 132 courses has been given to the 37 patients. All are evaluable for toxicity and efficacy. Toxicity was tolerable and not different from that presented in recent reports. Only four patients had to definitively stop therapy for toxicity, one of them for cardiotoxicity; a dose modification or a transient suspension of therapy occurred in 18% of treatment cycles. One hypothyroidism with anti-thyroglobulin and anti-microsome antibodies was observed. We observed eight major responses (21.6%), usually of short duration (2-6 months). Most responses occurred in superficial lesions. One patient remains in complete remission, as therapy is stopped for 40 months. Immunological parameters, although demonstrating induced immunostimulation, did not correlate with clinical outcome. With an overall response rate of 21.6%, we confirm the activity of interleukin-2 in melanoma, as previously reported by others.

Adult↗
PubMed1991

[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors].

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.

Adolescent↗
PubMed1991

Neoadjuvant chemotherapy in operable breast cancer.

Primary chemotherapy in localised breast cancer may prevent tumour spread during surgical treatment and reduce proliferation of micrometastases. A randomised clinical trial, in 196 premenopausal and postmenopausal patients with operable (T2-3, N0-1b) breast cancer, was started in November 1983 at the Institut Curie to compare neoadjuvant and adjuvant regimens of chemotherapy with radiotherapy with or without surgery. The patients have been followed up for 35-70 months (median 54). A neoadjuvant group received two monthly cycles of intravenous doxorubicin/cyclophosphamide/5-fluorouracil before locoregional therapy and four cycles subsequently. Six monthly cycles following locoregional therapy were administered to the adjuvant group. Because of inclusion of postmenopausal and/or node-negative patients, compliance was less than optimal in 39 patients who were analysed separately according to actual dose received. Tumour response, evaluated after two cycles of neoadjuvant chemotherapy, was significantly associated with dose (P = 0.003). Survival showed a slight non-significant advantage for the neoadjuvant group. Survival plotted by actual dose was also similar. Neoadjuvant chemotherapy was safe and at least as effective as the adjuvant regimen. Patients have been accrued to a subsequent larger trial of chemotherapy as first-line treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Phase I trial with recombinant interleukin-2 (rIL-2): immune activation by rIL-2 alone or following pretreatment with recombinant interferon-gamma.

Alterations of immunological parameters were analysed in patients with advanced malignancies during a phase I trial with rIL-2. Five-day infusions of rIL-2 at doses from 1 x 10(6) to 24 x 10(6) biological response modifiers program (BRMP) U/m2 per day were given to 29 patients, with a minimum of three patients per dose. The dose of 24 x 10(6) U/m2 per day was the maximal tolerated dose (MTD). Immunological parameters were analyzed at days 0, 8 and 11 of the rIL-2 courses. Following a leucopenia during rIL-2 infusion, a lymphocytosis was found in all patients except one. The lymphocytosis peaked at day 8 and was detected at doses of rIL-2 as low as 1 x 10(6) U/m2 per day, reaching a plateau at a dose of 16 x 10(6) U/m2 per day. Although all lymphocyte subsets were increased in patients receiving rIL-2, some patients had predominant T cells (CD3+, NKH1(CD56)-), others had predominant natural killer (NK) cells (CD3-, NKH1 (CD56)+), and yet others showed a mixed profile. A strong induction of cells cytotoxic for K562 targets was found in all patients at days 8 and 11. Eighteen patients received, 1 month later, a second treatment in which infusion of rIL-2 was preceded by a course of 5 days infusion of 2 x 10(6) U/m2 per day recombinant interferon-gamma (rIFN-gamma). The infusion of rIFN-gamma prior to rIL-2 had no effect on the rIL-2-induced alterations of immunological parameters. Taken together, our results suggest that immune stimulation by rIL-2 occurs even at low doses and is maximal at a dose below the MTD; and that pretreatment with low-dose rIFN-gamma does not modify the immune stimulation by rIL-2.

Cytotoxicity, Immunologic↗
PubMed1990

Scintigraphic study of radiolabelled interferon-alpha in osteosarcoma patients.

Interferon-alpha is currently under evaluation as an antineoplastic agent in several types of tumour. Despite its clear in vitro effects, the effectiveness of interferon in vivo is limited. To assess whether this discrepancy reflects pharmacokinetic limitations, the authors analysed interferon distribution in 2 osteosarcoma patients by scintigraphy using 123I-interferon-alpha-2a. Numerical analysis of the scintigraphic records demonstrated that the main organs of elimination were the kidneys, when the calculation was made on the basis of surface area. On the other hand, the apparent total uptake by liver (whose projection surface--i.e. the area exposed to the lens--is greater) was higher, reaching about 25 to 30% of the injected dose. The projection surface of the tumour was able to take up radiolabelled interferon in both cases, resulting in a 4-fold increase in the external radiation count compared with the equivalent region of the contralateral limb (although it is not possible to determine whether the label is present on the tumour itself or on the surrounding inflammatory cells). Thus, interferon-alpha seems able to reach at least the immediate neighbourhood of osteosarcoma mass.

Adult↗
PubMed1990

Problems and prospects of new immunotherapeutic approaches.

Active immunotherapy of cancer is based on the hyperactivation of the immune system of tumor-bearing patients. Interleukin 2 (IL2) has proven to be the most potent immunostimulant used so far. Therapeutic activity of IL2 and IL2-activated lymphocytes has been reported in the treatment of certain tumors such as metastatic melanoma and renal carcinoma. Effectiveness is related to the dose of IL2 administered to the patients, as are important toxic effects. Other cytokines, such as interferon (IFN) and tumor necrosis factor (TNF), are used for their direct effect on malignant cells, particularly those of the lymphoid lineage. The development of these new immunotherapeutic approaches will depend on the quality of their scientific bases, the clinical follow-up of the toxic effects, and the social management of the costs.

Cytokines↗
PubMed1989

[Metastatic breast cancer. Chemotherapy with adriamycin, vindesine, cyclophosphamide and 5 FU. Value of continuous 5 FU perfusion. Results of controlled trials].

Ninety-four patients with metastatic breast cancer were entered in a prospective randomised trial comparing 2 schedules of the same combination chemotherapy. Group I consisted of 46 patients, treated in a monthly three day course with adriamycin (ADM), cyclophosphamide (CPM), vindesine (VDS) and 5 fluoro-uracil (5 FU). Group II included 48 patients who received the same total monthly doses in 4 injections of ADM, CPM, VDS on days 2, 5, 16, 19 of each month together with a continuous infusion of 5 FU over a total of 10 days (days 1-5 and 15 and 19). Patient characteristics in the 2 groups as regards essential prognostic parameters were identical. We observed no difference in myelosuppression between the 2 groups. There were fewer gastrointestinal side effects in group II. Whereas complete alopecia occurred in 100% of patients in group I, only 33% of patients with the fractionated schedule totally lost their hair. The objective response rates at 8 months were 75 and 74% respectively, but the complete response rates (17.5 versus 28%) showed an advantage for group II. This advantage was not statistically significant. Durations of response were 15 months (group I) and 18 months (group II) and the median survival was 27 months in both. We conclude that prolonged low dose and fractionated administration of chemotherapy over 2 five day courses per month improves the therapeutic index and diminishes side effects.

Adult↗