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| |  ASCO: Zoladex (Goserelin) May Be Effective in Pre-Menopausal Breast Cancer NEW ORLEANS, LA -- May 24, 2000 -- The latest results from two large international studies presented this week at ASCO, identify that endocrine therapy with the LHRH agonist Zoladex (goserelin), alone or in combination with the antioestrogen, tamoxifen, could offer an effective, well tolerated, treatment option for pre-menopausal women with early breast tumours. For this patient group, chemotherapy is generally the accepted 'standard' treatment approach following initial surgery to remove the tumour. However, chemotherapy is frequently associated with distressing - and visible - side effects for the patient, including hair loss, nausea and vomiting (despite the use of anti-emetics), and the risk of life-threatening infection. Approximately three in every five cases of breast cancer occurring in pre-menopausal women are thought to be ER+ve, which means that the tumour is partially dependent on the hormone oestrogen to grow. Patients with tumours suitable for hormonal manipulation are therefore most likely to benefit from adjuvant endocrine therapies. Studies have already shown that those patients who suffer ovarian tissue damage during chemotherapy, hence lowering oestrogen production and inducing amenorrhoea - often permanently - seem to do better than those who continue menstruating after completion of treatment. However, the effect of chemotherapy on ovarian oestrogen production is unpredictable (between 31 percent and 89 percent of patients are rendered amenorrhoeic), depending on a number of factors, including the regimen used and the patient's age. Treatment with Zoladex, a Luteinising Hormone Releasing Hormone (LHRH) agonist, produces reliable, targeted suppression of ovarian oestrogen production ('oestrogen blockade'), reducing levels of the hormone in the blood down to those seen in post-menopausal women resulting in amenorrhoea in the majority of patients. Surgical removal of the ovaries or irradiation to stop their oestrogen production results in a permanent 'castration', as does chemotherapy-induced ovarian damage in a large proportion of cases. This brings on the onset of a premature menopausal state in these younger patients, with all the associated adverse effects, including an increased risk of cardiovascular disease and/or osteoporosis. Following cessation of Zoladex, a number of patients - dependent on their age and menopausal status prior to treatment - will return to normal ovarian function, hence avoiding continuation of the menopausal side effects and the long-term risks associated with permanent methods of ovarian ablation. The ZIPP (Zoladex in Pre-Menopausal Patients) study set out to explore whether the addition of 'Zoladex' to 'standard' adjuvant treatment (i.e. surgery with or without radiotherapy and/or chemotherapy and/or tamoxifen) was beneficial in terms of improved disease-free or overall survival in pre-/peri-menopausal women with early-stage breast cancer and similarly, if the addition of tamoxifen was beneficial. The study involved a total of 2710 young women. These patients have now been followed for an average of 5.5 years and the latest results presented today indicate that women who received 'Zoladex' had significantly better recurrence-free survival rates (HR = 0.80;CI 0.70-0.92; p<0.001) than those not treated with ‘Zoladex’ - irrespective of whether or not they also received tamoxifen and/or prior chemotherapy. The results are also suggestive of a longer overall survival in the 'Zoladex' treatment group (HR = 0.82; CI 0.67- 0.99; p = 0.04), although longer follow-up will be needed to confirm this trend. Although tamoxifen on its own reduced the risk of relapse this was not shown to be statistically significant. Joan Houghton from the Cancer Research Campaign Breast Cancer Trials Group presenting the 5.5-year median follow-up results of the ZIPP study believes these are very exciting findings for this patient population, 'young women at risk of breast cancer recurrence after initial surgery face some difficult decisions about follow-up treatment at the moment. Chemotherapy, while effective for a lot of women, is not without its problem side-effects which many of our patients find difficult to bear. 'Zoladex', on the other hand, is well tolerated and could offer this patient group an effective treatment option, whether given in combination with tamoxifen or not. Our study also illustrates that for those women who chose to undergo chemotherapy, addition of Zoladex is likely to further reduce risk of recurrence'. ZIPP is one of a number of studies reporting recently on the beneficial use of Zoladex in younger patients with early breast cancer given as adjuvant therapy either alone, or in combination with tamoxifen as an alternative or following 'standard' chemotherapy treatment. Further mature results from these trials, involving over 6,000 patients, will ultimately define the optimum role for Zoladex as an adjuvant treatment in pre-menopausal women with early breast cancer. At this stage, the trials indicate: The addition of Zoladex to 'standard therapy' (i.e. surgery followed by radiotherapy and/or chemotherapy and/or tamoxifen) provides statistically significant benefit, in terms of disease-free survival, over standard therapy alone. The combination of Zoladex plus tamoxifen is at least as effective as 'standard' chemotherapy* benefit from adding Zoladex (±tamoxifen) sequential to chemotherapy, particularly in those patients <40 years of age. Also reported at ASCO were the preliminary results of the ZEBRA (Zoladex in Early Breast Cancer Research Association Trial), involving 1,640 pre-/peri-menopausal women aged £50 years with stage II node positive breast cancer. This is the first study to directly compare the benefits of oestrogen suppression with an LHRH agonist with a 'standard' chemotherapy regimen following initial surgery (+ radiotherapy). Patients either received Zoladex (3.6mg every 28 days) for two years or chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) six x 28 day cycles. While the first efficacy results are due to report later this year, the initial tolerability data have already been analysed. These findings show that Zoladex was substantially more effective than CMF in inducing amenorrhoea (95.2 percent vs 60.2 percent following completion of 24 weeks' treatment). In addition, the ZEBRA results highlight the contrast in tolerability of the two treatment options; after 24 weeks, typical side effects of chemotherapy e.g. alopecia, nausea and vomiting (despite use of anti-emetics in over 97 percent of CMF patients) and infection were all substantially higher with CMF (43 percent vs. 4 percent, 56 percent vs. 5 percent and 13 percent vs. 5 percent, respectively). Menopausal symptoms such as vaginal dryness and hot flushes were initially lower with CMF (14 percent vs. 24 percent and 42 percent vs. 72 percent, respectively) but remained virtually unchanged post-treatment, whereas on cessation of Zoladex the incidence of these effects was markedly reduced. Further mature results from these two trials, together with those from the other trials which have already reported will ultimately define the optimum role for Zoladex as an adjuvant treatment in pre-menopausal women with early breast cancer. Related Link: Zoladex (goserelin).
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