Discussion Summary 院際聯合討論會Oct 22, 2008 于三總



Discussion Summary 院際聯合討論會Oct 22, 2008 于三總

Uterine sarcoma is a rare cancer with poor prognosis. The symptom is non-specific and it’s characterized by histopathological diversity. Early diagnosis is essential because patients’ survival is correlated to tumor stage. However preoperative diagnosis is often difficult and definitive diagnosis is frequently achieved after pathological analysis of hysterectomies specimens. The importance of surgical staging is discussed and the need for careful review of the pathology. Some recent important trials have helped to give better evidence base on which to plan future treatment strategies. The routine place of adjuvant pelvic radiation seems limited as it only leads to improved local control. To date chemotherapy studies have equally failed to show a benefit. More trials are needed to address these issues.

Both adjuvant radiotherapy and chemotherapy are further treatment strategies in our hospital, according to the patient’s clinical condition and pathologic findings. However, relatively higher relapse rate was also noted. The combination of carboplatin, paclitaxel and pegylated liposomal doxorubicin appears to have good activity. However, toxicity and side effect should be taken into consideration. The combination of ifosfamide and cisplatin is another choice. Significant side effects including encephalopathy and bladder cystitis should use mesna and thiamine as prophylaxis. New targeted agents, such as Antiangiogenesis, vandetanib and Avastin may offer more promising results in the future.

Reference

Clinical outcome and prognostic factors in 100 cases of uterine sarcoma: experience in Helsinki University Central Hospital 1990-2001.

~~ Gynecol Oncol. 2008 Oct;111(1):74-81.

In this study clinical data on all uterine sarcoma patients treated at Helsinki University Central Hospital (HUCH) between 1990-2001 were retrospectively evaluated. One hundred patients met the study requirements: 40 cases were diagnosed as carcinosarcomas, 39 as leiomyosarcomas and 21 as endometrial stromal sarcomas. First-line treatment was surgery in 98% of the patients. Seventy-eight of the patients were treated by means of adjuvant therapy. A complete response was achieved in 80% and a partial response in 4% of the cases. The 2-, 5- and 10-year overall survival rates were 62%, 51% and 38% and disease-specific survival rates were 64%, 56% and 44% (all sarcomas). In multivariate analysis, stage, age, tumor size and parity were proven to have independent influences on overall survival, and stage, tumor size and parity also independently influenced disease-specific survival.

CONCLUSIONS: In this study, survival rates were better than in nearly all previous retrospective studies of uterine sarcomas. It seems that higher parity could have a negative influence on survival in cases of uterine

Combined vascular endothelial growth factor receptor/ epidermal growth factor receptor blockade with chemotherapy for treatment of local, uterine and metastatic soft tissue sarcoma. ~ Clin Cancer Res. 2008 Sep 1;14(17):5466-75.

Vandetanib (AstraZenca), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, was evaluated alone and with chemotherapy in vitro and in vivo in three human STS nude mouse xenograft models of different STS locations (muscle, uterus, lung), stages (primary, metastatic), and subtypes (leiomyosarcoma, fibrosarcoma, uterine sarcoma: luciferase-expressing MES-SA human uterine sarcoma cells surgically implanted into uterine muscularis with bioluminescence tumor growth assessment; developed by us).

CONCLUSIONS: Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo, where it also affects the tumor-associated microenvironment. Given the urgent need for better systemic approaches to STS, clinical trials evaluating vandetanib, perhaps with low-dose chemotherapy, seem warranted.

Role of thiamine in managing ifosfamide-induced encephalopathy

~ J Oncol Pharm Pract. 2006 Dec;12(4): 237-9.

Encephalopathy is a well known side effect of ifosfamide, developing in approximately 10-30% of patients exposed to the drug. It is generally reversible after discontinuing the therapy; however cases of fatal neurotoxicity have been reported. Methylene blue is commonly used in the treatment and prophylaxis of ifosfamide induced encephalopathy; however its efficacy is moderate at best. We report here the utility of thiamine in both treating and preventing ifosfamide induced neurotoxicity in three patients. With the use of intravenous thiamine encephalopathy resolved in all of our patients within a mean time of 17 hours (range 10-30 hours). In three cycles where thiamine was used as prophylaxis no evidence of ifosfamide induced encephalopathy was seen. Thiamine appears to be a safe and effective treatment for reversing encephalopathy resulting form ifosfamide infusion, without any significant side effects.

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