Efficacy and safety of preservative-free timolol 0.1% gel in open-angle glaucoma and ocular hypertension in treatment-naïve patients and patients intolerant to other hypotensive medications.

GOALS: To assess the efficacy and safety of preservative-free timolol 0.1% gel in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: In this multicenter, open-label, non-controlled clinical trial in Algeria, treatment-naïve patients with intraocular pressure (IOP)>20mmHg and<31mmHg (treatment-naïve patients, group 1) and patients with IOP controlled by current ocular monotherapy but presenting with local intolerance in at least one eye (intolerant patients; group 2) were eligible. Timolol gel was administered once daily in the morning for 84 days. The primary efficacy criteria were reduction in IOP (group 1) and maintenance of baseline IOP (group 2). RESULTS: Overall, 93 patients were included (53 in group 1, 40 in group 2). All patients in group 2 had been previously treated with preserved eye drops. In group 1, patients showed a significant reduction in IOP with mean changes in the worse eye of -10.3±3.0mmHg at D28 and -10.8±2.5mmHg at D84 (P<0.0001). In group 2, the maintenance of efficacy on IOP at D84 was satisfactory in 91.7% of patients (worse eye). Preservative-free timolol gel was well tolerated in both groups. In group 2, the overall symptom score was significantly reduced from 8.6±5.1 to 0.9±1.6 at D28 and 0.7±1.2 at D84 (P<0.0001), and the overall ocular sign score from 3.7±2.1 to 0.8±1.0 at D28 and 0.6±0.8 at D84 (P<0.0001). CONCLUSIONS: This preservative-free timolol 0.1% gel was effective in decreasing IOP in treatment-naïve patients and in controlling IOP and reducing ocular signs and symptoms in patients intolerant to their previous preserved medications.

[Therapeutic intensification and autotransplantation of hematopoietic stem cells in metastatic breast cancers]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques dans les cancers du sein métastatiques.

The first studies on intensive chemotherapy for metastatic breast cancer conducted in the 80s were disappointing. Despite good response rates, the duration of remission was short and long-term survivals exceptional. Nevertheless, these phase I and II trials helped to develop a better understanding of the potential indications of this new therapeutic approach and apprehend its technical aspects. Over the last 5 years, considerable progress has been made in grafting techniques and hematopoietic support greatly improving the safety of the method. Notwithstanding the financial considerations involved, it must be noted that the efficacy autologous stem cell support, in terms of recurrence-free overall survival, has not yet been demonstrated although the (controversial) results of two randomized controlled trials have recently been published. In France, the PEGASE programs for the study of autologous stem cell support in breast cancer have been developed in an attempt to elucidate the question.

[High-dose therapy and hematopoietic cell autotransplantation in the treatment of adult gynecologic tumors]. / Intensification thérapeutique et autotransplantation de cellules souches hématopoïétiques dans le traitement des tumeurs gynécologiques de l'adulte.

Autologous bone marrow transplantation for the treatment of gynecologic tumors in adults remains an uncommon therapeutic approach. The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and disease-free survival are not convincing. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in France. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Randomized studies have to be done to precisely define the interest of high-dose therapy in terms of response and disease-free survival for the treatment of ovarian carcinomas.

High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults.

BACKGROUND: A Phase I-II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed. METHODS: Thirty-nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500-12,500 mg/m2), carboplatin (875-1225 mg/m2), and etoposide (1000-1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin- or carboplatin-based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered. RESULTS: The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and enterocolitis. Seven patients (18%) died of therapy-related be explored and the maximum tolerated doses of this three-drug regimen remain to be determined. CONCLUSION: This tandem therapeutic regimen is able to overcome resistance to a platinum-based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients.

[Therapeutic intensification and hematopoietic stem cell autotransplantation in the treatment of solid tumors in adults: principles, realization and application to the treatment of germ cell, trophoblastic, breast, ovarian and small-cell bronchial tumors. 1]. / Intensification thérapeutique et autotransplantation de cellules-souches hématopoïétiques dans le traitement des tumeurs solides de l'adulte: principes, réalisation et application au traitement des tumeurs germinales, trophoblastiques, mammaires, ovariennes et bronchiques à petites cellules. Première partie.

Autologous bone marrow transplantation for the treatment of solid tumors in adults remains an uncommon therapeutic approach. The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. For the treatment of primary chemoresistant gonadal germ-cell tumors, the possibility to cure the patients and the interest of high-dose therapy with autologous bone marrow transplantation are clearly demonstrated. As consolidation for the treatment of poor prognosis tumors, the place of high-dose therapies remains moot. For the treatment of chemoresistant extragonadal germ-cell tumors, especially for primary mediastinal tumors, the level of resistance to cisplatin-based chemotherapy regimens is generally too high to be overcome by intensive therapies given as single course or as tandem courses. However in association with debulking surgery, this therapeutic approach has to be considered for some patients. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and on disease-free survival are not evident. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in Europe. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Once again, randomized studies have to be done to precisely define the place of high-dose therapy. In the land of small-cell lung carcinomas, high-dose therapy is actually forsaken by most of authors, even for limited diseases. The results of previous studies are disappointing. Moreover, occult medullary micrometastases involvement is frequent, once again even in limited diseases. However new therapeutic associations, as the ICE regimen (IFM, Carboplatin, VP-16) delivered as single or tandem therapy, have to be studied, especially as early consolidation therapy for the treatment of limited small-cell lung carcinomas.

The route of maternal IgM transport to the rabbit fetus.

The route of IgM transport to the rabbit fetus was investigated by comparing its localization with that of IgG in the yolk sac splanchnopleure and uterine tissues using direct immunofluorescence and immunodiffusion analysis. IgM was first detected in fetal serum at 20 days of gestation but was present in uterine fluid at 18 days, the earliest stage tissues and fluids were examined. IgM was co-localized with IgG in the yolk sac endoderm basement membrane and in the vascular mesenchyme of the yolk sac splanchnopleure providing evidence of its transport to fetal blood; it was also present in vesicles in the yolk sac endoderm. IgM could not be detected in uterine fluid of nonpregnant uterine horns of rabbits unilaterally pregnant. Human IgM injected into the maternal circulation was readily transported to the uterine fluid and across the yolk sac splanchnopleure to fetal blood indicating that IgM secreting plasma cells, found to be present in the uterine stroma, contributed little towards IgM in the uterine fluid. Degenerating paraplacental decidual tissue, a feature of rabbit pregnancy, is suggested to be a major route for maternal immunoglobulin transport to the uterine fluid.