Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors

Villa, Erica; Ferretti, Ilva; Grottola, Antonella; Buttafoco, Paola; Buono, Maria Grazia Del; Giannini, Francesco; Manno, Mauro; Bertani, Helga; Dugani, Aisha; Manenti, F.

doi:10.1054/bjoc.2000.1534

Cited by 95 publications

(76 citation statements)

References 18 publications

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“…Compared with HCCs expressing wtER, HCCs with variant ER (vER) had more aggressive clinical features and insensitivity to tamoxifen [23,24]. In a preliminary, prospective, randomized study of 45 patients with HCC characterized by vER, patients treated with megestrol had a significantly longer median survival time than untreated patients (19 months vs. 7 months; p = .0090) [25]. Antiandrogen therapies have also failed to improve survival in randomized studies in patients with advanced HCC [16,26].…”

Section: Hormonal Therapymentioning

confidence: 99%

Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

2006

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Worldwide, hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death. In the U.S., 18,510 new cancers of the liver and intrahepatic bile duct are expected in 2006, with an estimated 16,200 deaths. The incidence rates for HCC in the U.S. continued to rise steadily through 1998 and doubled during the period 1975-1995. Unresectable or metastatic HCC carries a poor prognosis, and systemic therapy with cytotoxic agents provides marginal benefit. A majority of HCC patients (>80%) presents with advanced or unresectable disease. Even for those with resected disease, the recurrence rate can be as high as 50% at 2 years. Because of the poor track record of systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology community for decades. However, with the arrival of newly developed molecularly targeted agents and the success of some of these agents in other traditionally challenging cancers, like renal cell carcinoma, there has recently been renewed interest in developing systemic therapy for HCC. This review attempts to concisely summarize the historical perspective and the current status of systemic therapy development in HCC. The Oncologist

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Section: Hormonal Therapymentioning

confidence: 99%

Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?

2006

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“…This suggests that the direct effect of megestrol acetate on the growth of HepG2 cells can only be achieved at higher dosages, and high dosages are needed clinically for inhibition of growth of HCC in patients. The high IC 50 for megestrol acetate value may also explain the equivocal and discrepant results of the limited number of studies using megestrol acetate for the treatment of inoperable HCC (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported to cause minor reduction of tumor size and prolonged survival time in HCC (26). A small controlled trial has shown that megestrol acetate favorably influence the course of advance HCC and improve patient survival (27). Quite apart from its antiestrogen mechanisms, megestrol acetate impacts positively on the quality of life in patients with advanced malignancy (28).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Megestrol Acetate on Growth of HepG2 Cells In vitro and In vivo

Zhang¹,

Chow

2004

Clinical Cancer Research

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Purpose: Hepatocellular carcinoma (HCC) is generally considered as a sex hormone-dependent tumor, and hormonal therapy has been proposed as a strategy for the treatment of HCC. The aim of the study is to investigate the effect of megestrol acetate, a synthetic progesteronal agent, on growth of HepG2 cells in vitro and in vivo.Experimental Design: Cell growth in vitro was assessed by a colormetric method, and cell growth in vivo was assessed by tumor volumetrics. Results: Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose-and time-dependent manners with an IC 50 of 260 M (24-h incubation).The growth of HepG2 cell-transplanted tumors in nude mice was also inhibited by i.p. injection of megestrol acetate (10 mg/ kg/day). The tumor volumes of the megestrol acetate-treated group regressed to 59% of controls by week 6 and to 41% of controls by week 13. Apoptosis following G 1 arrest was observed in megestrol acetate-treated cells and may be a mechanism through which megestrol acetate inhibits HepG2 cells. Megestrol acetate was also demonstrated to have a beneficial effect on the weight gain of tumor-bearing nude mice, and the mean weight of the megestrol acetate-treated animals was higher than that of controls from week 4 of the treatment period, and the differences were statistically significant in week 5 and 6 (P < 0.05, compared with controls). No significant survival advantage was, however, demonstrated in the treatment group.Conclusions: This study showed that megestrol acetate inhibited the growth of HepG2 cells grown in vitro and in vivo. These data provide useful information for clinical study of megestrol acetate for the treatment of HCC.

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“…Several prospective randomized trials and a systematic review of tamoxifen in patients with advanced HCC have failed to show a survival benefit or improved functional status (Castells et al, 1995;Chow et al, 2002;Nowak et al, 2004;Barbare et al, 2005). One possible reason for the lack of efficacy may be the presence of variant ERs in some of these tumors (Villa et al, 1996;Villa et al, 2001). Tamoxifen may also function as a potential inhibitor of p-glycoprotein, the MDR (multidrug resistance) gene www.intechopen.com product, and this has led to trials of tamoxifen combined with various chemotherapeutic agents.…”

Section: Tamoxifenmentioning

confidence: 99%