Endometrial cancer treatment

Meg estrolAceta.te. This compound is used outside the United States as an oral contraceptive. In the United States, it is used for the paUiative treatment of breast cancer and endometrial cancer, or as an adjunct to other therapies. Its use has been associated with an increased appetite and food intake and has been evaluated in the treatment of anorexia and cachexia (107). 

Interestingly, while it has been reported that the inhibition of cell growth by carotenoids in colon (Palozza et al., 2001b, 2007a) as well as in prostate (Williams et al., 2000) adenocarcinoma cancer cells was independent of p53 and p21 status, HL-60 cells increased their p21 expression as a consequence of the treatment with p-carotene (Palozza et al., 2002b). In addition, the antiproliferative effects of P-carotene required p21 expression in human fibroblasts (Stivala et al., 2000). In contrast, mammary and endometrial cancer cells decreased p21 levels, following lycopene treatment (Nahum et al., 2001). 

Chan S (2002) A review of selective estrogen receptor modulators in the treatment of breast and endometrial cancer. Semin Oncol 29 129... 

Droloxifene (3-hydroxy-tamoxifen) behaves as an estrogen agonist in bone tissue and several lipid and coagulation markers in castrated rat models and does not show stimulation of the endometrial epithelium in preclinical studies (Ke et al. 1997). Endometrial stimulation has, however, been observed in clinical trials, which, together with the fact that as an estrogen agonist it is ten times less potent than tamoxifen in bone tissue and lipid metabolism (Hendrix et al. 2001) and that in a recent head-to-head comparison with tamoxifen droloxifene was demonstrated not to be superior in any parameter of breast cancer treatment efficacy (Buzdar et al. 2002), has resulted in cancellation of its clinical development. 

The SERMs that belong to the benzopyrans group form a large group of drugs (Fig. 2.5), several of which are at early stages of clinical development for the treatment of hormone-dependent breast cancer and endometrial cancer. 

EM-800 (SCH-57050) and its active metabolite EM-652 (acolbifene, SCH-57068), are highly potent antiestrogens in human breast and uterine cancer cells in vitro as well as in vivo in nude mice and are currently undergoing clinical trials in the treatment of hormone-dependent breast cancer and endometrial cancer (Labrie et al 1999). Acolbifene shows a higher capacity of binding to... 

Fig. 10.8. Hazard ratio of presenting an endometrial cancer as the consequence of treatment with tamoxifen or raloxifene (MORE study). Reproduced with permission from Cuzick et al. (2003)...

In a case-control study (van Leeuwen et al. 1994) in which 98 cases of invasive endometrial carcinoma were diagnosed at least 3 months after diagnosis of primary breast cancer, it was observed that the use of tamoxifen was associated with a RR of 1.3. The risk appeared to have a tendency to increase during treatment, from 0.6 for less than a year to 3.0 for more than 5 years of treatment. It should be noted that the accumulated dose of tamoxifen was significantly associated with risk of endometrial cancer. However, the average daily dose used (20-40 mg/d) did not seem to influence risk. Other authors have also observed that the increase in risk is only detected when a determined accumulated dose is attained (van Leeuwen et al. 1994 De Muylder et al. 1991). 

According to results from clinical trials, the agonistic effects of tamoxifen detected in animals were also observed in the human uterus as it produces a trophic effect and an increase in the incidence of endometrial pathology, which is related to endometrial thickening (> 4 mm). Its use seems to be associated with an increase in endometrial cancer, which is related to the length of treatment and the accumulated dose of tamoxifen. Nevertheless, these tumors do not seem to be more aggressive or to have a worse prognosis than those found in women who do not follow this treatment or who receive hormone therapy. 

Swerdlow AJ, Jones ME, British Tamoxifen Second Cancer Study Group (2005) Tamoxifen treatment for breast cancer and risk of endometrial cancer a case-control study. J Natl Cancer Inst 97(5) 375-384... 

In the same way as estrogens, progestogens are used in the treatment of several other conditions such as infertility, endometriosis, in the management of certain breast and endometrial cancers, and either alone or in combination with estrogens in the treatment of menstrual disorders, among others. The therapeutic doses required in the treatment of many of these diseases are often significantly larger than those employed in contraception. 

Tamoxifen is on oestrogen-receptor antagonist. It is used in post-menopousol women with oestrogen-receptor-positive metastatic breast cancer at a dose of 20 mg doily. It con also be used in combination with chemotherapy. Severe side-effects ore infrequent however, it is associated with a small risk of endometrial cancer. Patients should be informed and reassured that the benefits of the treatment at this dose outweigh the risk. 

The administration of tamoxifen necessitates routine gynaecological monitoring since uterine fibroids and endometrial changes may occur with its use. Prior to starting treatment, patients should be informed of the small risk of endometrial cancer associated with tamoxifen therapy. 

Although there have been some efforts to combine chemotherapy and radiation for patients with ovarian cancer, these cancers are usually advanced at presentation, limiting the role of local treatment. For patients with endometrial cancer, the possible role of combined adjuvant treatment is just beginning to be explored by the multi-institutional clinical trials groups. 

The most frequent adverse reactions to tamoxifen include hot flushes, nausea, and vomiting. The incidence of endometrial cancer shows a twofold increase in women on longterm treatment with tamoxifen. 

With regard to hormone use in the adjuvant setting a systematic review in the Cochrane database of six trials involving 4351 women concluded Current evidence does not support the use of adjuvant progestogen therapy in the primary treatment of endometrial cancer (see Martin-Hirsch et al., 1999). 

Tamoxifen is a partial estrogen agonist in breast and thus is used as a treatment and chemopreventative for breast cancer. Tamoxifen is a full agonist in bone and endometrium, and prolonged use of tamoxifen leads to a fourfold to fivefold increase in the incidence of endometrial cancer. See Chapter 56 for a detailed discussion of the use of tamoxifen in breast cancer. 

The chief therapeutic uses of estrogens and progestins are as oral contraceptives and hormone replacement therapy. Progestins and SERMs are also important agents in the treatment of osteoporosis, breast cancer, endometrial cancer, and infertility. 

Certain tissues of the female reproductive tract, which are subject to the trophic action of hormones, exhibit a high frequency of neoplasia. Cancer of the breast, the second most common form of cancer in American women, and the rarer endometrial cancer in women, are often responsive to treatments with estrogens or progestins. The toxicity of these hormonal treatments compared with standard cancer chemotherapy is low. 

Treatment duration >5 yr may provide no further benefit and increase risk of endometrial cancer for some women reevaluate the need for continued therapy... 

It has become apparent that reduction in the dose of the constituents of oral contraceptives has markedly reduced mild and severe adverse effects, providing a relatively safe and convenient method of contraception for many young women. Treatment with oral contraceptives has also been shown to be associated with many benefits unrelated to contraception. These include a reduced risk of ovarian cysts, ovarian and endometrial cancer, and benign breast disease. There is a lower incidence of ectopic pregnancy. Iron deficiency and rheumatoid arthritis are less common, and premenstrual symptoms, dysmenorrhea, endometriosis, acne, and hirsutism may be ameliorated with their use. 

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