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AEZS-108 was less toxic and more efficacious than doxorubicin in inhibiting the growth of LHRH receptor–positive human endometrial and ovarian cancers xenotransplanted into nude mice.
Each treatment cycle consisted of 21 days in which AEZS-108 267 mg/m2 (equimolar to 76.8 mg/m2 of free doxorubicin) was administered on day 1 as a 2-hour intravenous infusion
A Phase II study of zoptarelin doxorubicin in EC patients showed activity, including those previously treated with platinum-taxane
The study is expected to include 500 EC patients progressing after prior therapy with platinum-taxane-based chemotherapy.
Dr. Richard Sachse
Potential benefits of this targeted approach may include enhanced efficacy and a more favorable safety profile with lower incidence and severity of adverse events, as compared to doxorubicin. If Zoptrex™ is approved as a therapy for endometrial cancer, we intend to develop it for these additional indications. In addition, based on the results of Phase 2 studies, we believe that Zoptrex™ holds promise to prove its efficacy for the treatment of ovarian and prostate cancer."
During the ASCO Annual Meeting, the Company provided an update regarding its progress with Zoptrex™ during one-on-one meetings with oncological key opinion leaders. Dr. Sachse described his interactions with ASCO attendees as promising, stating as follows: "I'm pleased and gratified by the continuing expressions of support for our work on Zoptrex™. The oncologists with whom we met were pleased to learn of our progress toward the completion of our Phase 3 clinical trial and seemed to be as excited as we are about the contribution that our new targeted oncology therapy could make to the treatment of one of the most severe forms of cancer."
Endometrial Cancer Highlights
Best Poster (# B17- 0067): The German study group for gynaecologic oncology (AGO = arbeitsgemeinschaft gynäkologische onkologie) represented by G Emons , University Hospital Goettingen, presented its results to the Phase II-study with a targeted cytotoxic LHRH- analogue (AEZS-108) in patients with LHRH – receptor positive endometrial cancer: protocol AGO-GYN 5, AGO-study group. Endometrial cancers (EC) commonly express receptors for luteinising hormone releasing hormone (LHRH). AEZS-108 is a targeted cytotoxic drug where [D-Lys(6)]-LHRH is linked to doxorubicin. Efficacy and toxicity of AEZS-108 was assessed in endometrial cancer. A promising clinical benefit rate of 72% was shown. OS after single agent AEZS-108 is similar to that reported for modern triple combination chemotherapy, but was achieved with distinctly lower toxicity.
A Multicenter Phase 2 Trial (AGO-GYN5)
The overall response rate was 23%. Two (5%) patients had a CR that lasted at least 8 months and 23 months. Eight (19%) patients had PR. Twenty (47%) patients met the criteria for stable disease, resulting in a clinical benefit rate of 70%. Nine (21%) patients had progressive disease, and 4 patients were not evaluable (1 noncancer death before cycle 2; 3 patients with tumor assessments not evaluable for reviewer). Both patients with CR and 6 women with PR had type I disease. One patient with PR had a serous EC and another had a clear cell EC. Thus, of the 10 patients with objective responses, 8 had type I and 2 hadtype II disease.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921259/
Grades 1 and 2 endometrioid cancers are type 1 endometrial cancers. Type 1 cancers are usually not very aggressive and do not spread to other tissues quickly.Type 1 endometrial cancersare thought to be caused by excess estrogen. They sometimes develop from atypical hyperplasia, an abnormal overgrowth of cells in the endometrium (see the risk factors section).
A small number of endometrial cancers are type 2 endometrial cancer . Type 2 cancers are more likely to grow and spread outside the uterus, they have a poorer outlook (than type 1 cancers). Doctors tend to treat these cancers more aggressively. They don’t seem to be caused by too much estrogen. Type 2 cancers include all endometrial carcinomas that aren’t type 1, such as papillary serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, and grade 3 endometrioid carcinoma. These cancers don’t look at all like normal endometrium and so are called poorly differentiated or high-grade.http://www.cancer.org/cancer/endometrialcancer/...-endometrial-cancer
Second-Line Chemotherapy Experience
Although chemotherapy has shown an important role in high-risk disease, substantial room for improvement exists. Combination regimens are the most active, but in measurable disease populations responses are observed in only ∼50% or patients, and a complete response is infrequently observed. Both the PFS and survival times have been improved, yet the 5-year survival rate for patients with advanced/recurrent measurable disease patients is <10%, and for those with stage III disease it is typically around 50%–60% [19, 20, 22, 25]. After primary therapy with combination regimens, the efficacy of second-line chemotherapy is particularly limited (Table 3). Antimicrotubule agents have shown the most promise. In a population in which 91% had received doxorubicin–platinum chemotherapy, paclitaxel produced a RR of 25%; the epothilone B analog ixabepilone produced an RR of 12% in a population in which 94% had received prior paclitaxel [16, 28]. Interestingly, docetaxel, which had shown activity in paclitaxel-treated breast and ovarian cancer patients, produced an RR of only 8% (80% had received prior paclitaxel) in patients with advanced/recurrent endometrial cancer . After failure of primary chemotherapy, there is no established active second-line agent in this disease. Understanding the processes by which tumors develop resistance is critical, and defining which patients have the best chance to respond to established or novel therapies is our greatest challenge.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227900/
Efficacy and Safety of AEZS-108 (LHRH Agonist Linked to Doxorubicin) in Women With Advanced or Recurrent Endometrial Cancer Expressing LHRH Receptors
A Multicenter Phase 2 Trial (AGO-GYN5)
Fifty percent of patients progressing on AEZS-108 therapy received carboplatin/paclitaxel as the next line of treatment. This might have also contributed to the good median OS observed in our trial but cannot have influence on the TTP. On the contrary, 8 patientshad received carboplatin/paclitaxel treatment before AEZS-108 therapy. Two of these had anobjective response, and 3 achieved a stable disease on AEZS-108 treatment.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921259/#R3
high-grade ? (Typ2)Treatment of Advanced or Recurrent Endometrial Carcinoma with Doxorubicin in Patients Progressing after Paclitaxel/Carboplatin
Our goal was to investigate the activity of doxorubicinin the second-line setting in patients who progressed after paclitaxel/carboplatin adjuvant treatment
Discussion:Our findings suggest that doxorubicin’s utility in the second-line setting for advanced/recurrent endometrial carcinoma is limited, but prospective testing of this agent is warranted. In the near future, an open-label randomized phase III trial of second line AEZS-108 (doxorubicin linked to LHRH analog) versus doxorubicin in patients progressing after platinum/taxane-based chemotherapy will be open to accrual, and will define the activity of second-line doxorubicin in malignancy. Although our retrospective analysis is limited by evaluation of a small number of patients, we feel that patients with recurrent endometrial carcinoma should be encouraged to consider clinical trials of novel therapies in recurrent endometrial carcinoma since there is no standard second-line therapy with established efficacy.
Das kann doch nur was werden!
Eben hatten wir ein "All today high" :-)
abwarten was morgen uns der tag bringt.mußte eben mal meine lese brille holen weil ich nicht glauben wollte das wir 2,5%in plus sind.....ist das wahr???