leo
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Joined: 23 Sep 2004
Posts: 1574
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 Posted: Wed Oct 20, 2004 11:26 am Post subject: Re: Stage 4 Endometrial Cancer |
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Jane
I pasted below an excerpt from Up-to-Date. I hope it is helpful. As you know, the prognosis is not good, but there are some options available.
[quote]MANAGEMENT OF RECURRENT OR DISSEMINATED DISEASE ? Women with inoperable recurrent or advanced endometrial cancer can be treated with hormonal therapy, chemotherapy, or radiation.
Hormonal therapy ? Women with well-differentiated tumors that express estrogen (ER) and/or progesterone receptors (PgR) are more likely to experience a response to progestin therapy than those with hormone receptor-negative tumors. Several progestins (eg, hydroxyprogesterone caproate, medroxyprogesterone acetate) have been investigated, and they all have similar response rates (15 to 30 percent) [96]. An oral progestin (eg, megestrol acetate [160 to 320 mg per day]) is the agent of choice. The use of higher dosages (eg, 1000 mg/day) does not improve efficacy [97], and increases the likelihood of side effects. The duration of benefit is limited; average response duration is only four months, and mean survival is 10 months following the institution of therapy.
Tamoxifen, a selective estrogen receptor modulator (SERM), also appears to be effective in women with advanced and/or recurrent endometrial cancer, either alone or in combination with a progestin. Although preliminary results from a GOG trial using tamoxifen with either medroxyprogesterone acetate or megestrol acetate demonstrated response rates of 32 and 26 percent, respectively, the combination of tamoxifen and a progestin has not been shown to be more effective than progestin therapy alone [98].
Other SERMs are also active in women with advanced disease. As an example, arzoxifene, a third generation SERM, was associated with a response rate of 31 percent in 37 patients; all responders had progestin-responsive disease [99]. Arzoxifene is not commercially available in the United States. The antitumor efficacy of two available SERMs, toremifene and raloxifene, is unknown.
Gonadotropin-releasing hormone analogs have also been evaluated in patients with advanced endometrial cancer, with objective response rates between 9 to 28 percent; response rates are lower in the setting of prior progestin treatment [100-102].
The combination of hormone therapy and chemotherapy is discussed below.
Chemotherapy ? Both single agents and combination regimens of cytotoxic chemotherapy have been studied in women with advanced endometrial carcinoma.
Single agent therapy ? Doxorubicin, cisplatin, carboplatin and topotecan are all active as monotherapy, with response rates of 20 to 28 percent [96,103-105]. Most of these responses are partial and of short duration. As a salvage agent, paclitaxel has a reported overall response rate of 27 to 37 percent [106-108]. Dactinomycin had a 12 percent overall response rate in one GOG study [109].
Combination chemotherapy ? Although response rates for various combination regimens that include cisplatin and/or doxorubicin are slightly higher (36 to 67 percent), progression-free survival has generally been only four to eight months [78,110-115], and in randomized trials, there is no evidence that survival is prolonged with cisplatin plus doxorubicin compared to single agent therapy [116].
Paclitaxel-containing combination regimens have not been directly compared to single agent therapy. Early studies of paclitaxel with either carboplatin or cisplatin suggested response rates between 50 and 56 percent, and an improved progression free survival rate compared to historical experience with other regimens [117-119]. Moreover, these regimens may be associated with a long-term survival benefit in women with primary advanced endometrial adenocarcinoma with as well as the more aggressive nonendometrioid adenocarcinoma histologies (see "Papillary serous and clear cell endometrial tumors" below).
This was illustrated in a report in which 63 women with locally advanced or recurrent endometrial cancer received 28-day cycles of paclitaxel (175 mg/m2 over three hours) plus carboplatin (area under the concentration x time curve [AUC] 5 to 7) with or without radiation therapy [118]. Three-year overall survival rates for women receiving combined therapy for locally advanced disease were 39 and 62 percent for those with nonpapillary and papillary serous cancers, respectively. Furthermore, the median survival duration for patients treated with chemotherapy alone for recurrent disease was 15 months.
The superiority of paclitaxel versus nonpaclitaxel-containing combination regimens has been evaluated in at least three trials:
In a GOG trial that randomly assigned 314 women with advanced or recurrent endometrial carcinoma to doxorubicin plus either paclitaxel (24 hour infusion) or cisplatin, the group receiving paclitaxel did not have a better outcome in terms of response rates (40 versus 43 percent for doxorubicin plus cisplatin or paclitaxel, respectively), disease-free, or overall survival [120].
In contrast, better outcomes for paclitaxel-based chemotherapy have been suggested in two trials [121,122]. A French study randomly assigned 67 women with recurrent or advanced endometrial cancer to 21 day cycles of doxorubicin (60 mg/m2 day 1) plus cisplatin (50 mg/m2), or carboplatin (AUC 5) plus paclitaxel (175 mg/m2 over three hours) [121]. In a preliminary report, carboplatin/paclitaxel was associated with a higher response rate (35 versus 28 percent), and a greater likelihood of disease-free (35 versus 24 percent) and overall survival (41 versus 27 percent) at 15 months. There were no major differences in toxicity profile.
Similarly, GOG trial 177 randomly assigned 273 women with stage III or IV or recurrent endometrial cancer to doxorubicin (60 mg/m2) plus cisplatin (50 mg/m2) both administered on day one every three weeks, or the three drug combination of doxorubicin (45 mg/m2 on day 1), cisplatin (50 mg/m2 on day 1) plus paclitaxel (160 mg/m2 over three hours on day 2) with G-CSF support (TAP) [122]. Response rates were significantly higher with TAP (57 versus 34 percent), as was the duration of median progression-free survival (8.3 versus 5.3 months) and overall survival (15.3 versus 12.3 months). TAP was associated with more grade 3 neuropathy (12 versus 1 percent) and grade 3 symptomatic heart failure (three patients receiving TAP compared to none receiving doxorubicin plus cisplatin), although less grade 4 neutropenia (36 versus 50 percent).
Based upon these results, the GOG is currently conducting a randomized equivalency trial of TAP versus carboplatin plus paclitaxel in patients with measurable advanced and recurrent endometrial cancer.
Other chemotherapy combinations such as cisplatin and vinorelbine are also active and well tolerated [123]. Nevertheless, the demonstration of superiority of any combination regimen will require a randomized trial that shows a survival benefit.
Chemohormonal therapy ? Combinations of chemotherapy with hormonal treatment have also been extensively evaluated in women with advanced or recurrent endometrial cancer with some evidence of benefit.
In one study, 23 patients received carboplatin, methotrexate, and 5-fluorouracil, in combination with medroxyprogesterone acetate (300 mg orally each day) until progression (JMF-M regimen) [124]. Objective response was seen in 17 patients (74 percent), with two long-lasting complete responses (9 percent). The median response duration was more than 10 months (range 3 to 45+) and the median survival was more than 16 months (range 2 to 45+).
In a second series, fifty consecutive patients treated from 1978 to 1985 received melphalan, 5-fluorouracil, medroxyprogesterone acetate (MFP regimen) as first-line therapy, and 50 additional patients treated from 1987 through 1993 were prospectively treated with cisplatin, adriamycin, etoposide, and megestrol acetate (PAV-M) [125]. Response rates for MFP versus PAV-M were not statistically different, but there was a significant advantage for PAV-M in two-year (45 versus 14 percent), five-year (30 versus 5 percent), and median survival (22 versus 9 months, p = 0.008) in women with primary advanced endometrial adenocarcinoma. PAV-M also appeared to be better than MFP in patients with papillary serous and clear cell cancers (see below).
Summary ? It appears that combinations of chemotherapy and hormone therapy may represent optimal treatment for patients with advanced or recurrent endometrial cancer; the best regimen is unknown. Megestrol plus cisplatin and doxorubicin, PAV, or paclitaxel and carboplatin appear to be reasonable choices.
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Leonardo F - Webmaster Cancer Forums
Disclaimer: this information is for informational purposes only. It is not medical advice. |
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