The acute effects of goserelin on

The acute effects of goserelin on bone have also been evaluated by prospective trials of goserelin+/− adjuvant tamoxifen. The Zoladex in Premenopausal Patients trial randomized 89 women with early breast cancer to goserelin+/− tamoxifen, tamoxifen alone and no endocrine therapy. After 2 years of treatment there was a significant Protease Inhibitor Cocktail (EDTA-Free, 100X in DMSO) in BMD of 5% in patients receiving goserelin alone with partial recovery in BMD of 1.5% at 12 months post cessation of treatment [24]. The role of goserelin to protect against chemotherapy induced POI is controversial. However, the POEMS study recently reported preliminary results that are likely to increase the use of this therapeutic strategy [25]. POEMS randomised 257 premenopausal patients with ER-ve breast cancer to standard cyclophosphamide containing chemotherapy alone or with monthly goserelin 3.6mg. The primary endpoint was 2 year POI with secondary endpoints that included survival and pregnancies. POI rates were 22% in standard arm and 8% in the goserelin arm (p=0.03). There were more pregnancies in the goserelin arm (22 vs 13 p=0.05). Remarkably in this ER-ve population, disease free and overall survival were also improved in the goserelin arm. In conclusion, our data are the first to show that concomitant use of chemotherapy and goserelin may protect ovarian function sufficiently to prevent long term deleterious effects on bone turnover. In young women who experience POI as a result of chemotherapy it will be important that bone health assessment is carried out as part of their longer term follow up [26, 27].
Role of funding Source The OPTION trial was sponsored by the Anglo Celtic Cooperative Oncology Group with funding received from Cancer Research UK, Experimental Cancer Medicine Centre and the National Institute of Health Research UK (grant number C4831/A181). Study design, collection, analysis and interpretation of data, writing of the report and the decision to submit the article for publication was the responsibility of the authors with no involvement of the funding source.
Declaration of interest statement
Introduction Osteosarcoma is an aggressive bone neoplasm arising from primitive transformed cells of mesenchymal origin. It was such a fatal disease that “months to metastasis” rather than actual survival time, was used to measure the outcomes of treatment in studies of early stage. In the 1950s, there was no optional therapy that could significantly increase the survival rate, with a 5-year survival rate of 22% [1]. However, with the aid of effective chemotherapeutic drugs the survival rate of osteosarcoma has been significantly improved since the late 1970s [2,3]. Recently, the gold standard of osteosarcoma chemotherapy have been based on around 5 drugs; high-dose methotrexate (HDMTX) with leucovorin rescue, doxorubicin (adriamycin), cisplatin, ifosfamide, and etoposide [4]. Combinations of these drugs, mostly in the form of neoadjuvant as well as adjuvant MAP, are the current management for osteosarcoma [5], and various chemotherapy protocols are still under investigation. The experience with radiotherapy is limited, as osteosarcoma is long considered resistant to applicable doses of radiation. However, recent data suggest that the combined approach of irradiation with chemotherapy may be useful in patients who have microscopic residual tumor foci following intralesional resection [6]. With the advent of effective neoadjuvant chemotherapy in the 1970s, limb salvage surgery (LSS) has been taken as a potential treatment for osteosarcoma [7,8]. Usually, LSS has functional and physiological advantages over traditional amputative procedures when combined with neoadjuvant or adjuvant chemotherapy [9]. It is now generally accepted that LSS is indicative for localized osteosarcoma, while surgical amputation is adopted for high malignancy osteosarcoma. However, there are still some surgeons holding the view that immediate and aggressive removal of the tumor will prevent the progression of fracture-induced disease, and consequently amputation is considered to be a better option for osteosarcoma patients with pathologic fracture [10–13].