ONCOSTROL-40MG/160MG
Megestrol Acetate

Megestrol acetate is a synthetic progesterone derivative that is primarily used in the treatment of certain types of cancer, particularly breast and endometrial cancers. It is also used to manage appetite and weight loss in individuals with HIV/AIDS and to control symptoms of advanced stage breast or endometrial cancer.

Mechanism of Action of Megestrol Acetate:
Megestrol acetate works by binding to progesterone receptors in target tissues, including breast and endometrial tissue, thereby inhibiting the growth and proliferation of cancer cells. It also has anti-inflammatory and immunosuppressive properties, which contribute to its effectiveness in the treatment of cancer and its associated symptoms.

Clinical Applications of Megestrol Acetate:
 
Breast Cancer: Megestrol acetate is commonly used in the treatment of advanced breast cancer in postmenopausal women who have already undergone other forms of hormone therapy. It can also be used as a second-line therapy after chemotherapy for patients who have not responded to other treatments.
Endometrial Cancer: Megestrol acetate is also used in the treatment of endometrial cancer, particularly in women who are not candidates for surgery or radiation therapy. It is often used in combination with other medications, such as progestins, to help control the growth of cancer cells.
Palliative Care: Megestrol acetate is commonly used in palliative care for patients with advanced-stage cancer, particularly for those experiencing weight loss and loss of appetite. It has been shown to improve appetite and promote weight gain in these patients, as well as improve their overall quality of life.
 
Megestrol Acetate Dosage and Administration:

Megestrol acetate is available in several different forms, including oral tablets and suspension. The recommended dosage and administration will vary depending on the indication being treated and the patient's individual needs. It is important to follow the prescribing physician's instructions carefully and to report any side effects or changes in symptoms.

Megestrol Acetate Side Effects:

The most common side effects of megestrol acetate include weight gain, fluid retention, and changes in appetite. Other potential side effects may include nausea, vomiting, diarrhea, headache, and dizziness. Rare but serious side effects may include blood clots, stroke, and liver damage.

Cachexia is primarily caused by several cytokines, the most important of which are tumor necrosis factor (TNF)-, interleukin (IL)-1, interleukin (IL)-6, and interferon (IFN)-γ.
It is believed that TNF- works through a variety of mechanisms to produce a significant portion of the severe cachexia that can occur in patients who suffer from chronic infections and cancer.

New evidence suggests that TNF- and other inflammatory cytokines contribute to muscle wasting by inhibiting myogenic differentiation via an NF-κB-dependent pathway. This pathway is responsible for the process.

Increased levels of mitochondrial uncoupling proteins from TNF- also serve as an energy sink, and the protein blocks the activity of the enzyme lipoprotein lipase, which in turn promotes lipolysis in the body.

Both IL-6 and IL-1 play a role in the development of cachexia by interacting with other cytokines.

It appears that Megestrol acetate has direct anti-cytokine properties.

TNF, IL-6, and IL-1 are just a few of the cytokines that this medication significantly reduces.

Megestrol acetate has been shown to significantly reduce serum levels of IL-1 α and β and IL-6  production in peripheral blood mononuclear cells in patients with cancer.

It has been demonstrated that the drug can reverse the effects of anorexia and weight loss that are caused by treatments based on IFNα- and IL-2 in patients who have advanced metastatic cancer.

All evidences on data file and will be provided on request.

Brief History of Megestrol Acetate Development:

In 1959, Megestrol Acetate was successfully synthesized at Syntex(In January 1944, a pharmaceutical firm called Laboratorios Syntex SA (later Syntex Laboratories, Inc.) was established in Mexico City.). Megestrol Acetate was produced through a process that began with the synthesis of medroxyprogesterone acetate(Depo-Provera, as well as the generic name Depot Medroxyprogesterone Acetate (DMPA), is an injectable form of the progestin hormone medication known as medroxyprogesterone acetate (MPA)) at Syntex in the year 1957.

After hydroxyprogesterone caproate(Hydroxyprogesterone caproate (OHPC), sold under the brand names Proluton and Makena among others, is a progestin medication ) in 1954 and medroxyprogesterone acetate in 1957, Megestrol Acetate was the third synthetic form of progesterone to be made into a drug.

In 1963, British Drug Houses in the UK started selling the Megestrol Acetate with ethinylestradiol (EE) as an oral contraceptive under the brand name Volidan (4 mg Megestrol Acetate and 50 g EE tablets). In 1964, Serial 28 (1 mg MGA and 100 g EE tablets) and Volidan 21 (4 mg MGA and 50 g EE tablets) and Nuvacon (2 mg MGA and 100 g EE tablets) followed in 1967.By 1965, it was also sold under the brand name Delpregnin (5 mg of MGA and 100 g of mestranol tablets).After reports in the early 1970s that birth control pills with MGA caused a lot of venous thromboembolism, the pills were taken off the market.(Please keep in mind megestrol acetate alone doesnt exist earlier.)

After it was taken off the market, Megestrol Acetate was eventually brought back to treat cancers that respond to hormones. In 1951, it was discovered that progesterone helped treat endometrial hyperplasia, and in 1959, it was discovered that progestins helped treat endometrial cancer.(hyperplasia is a stage before cancer in which there is increase in the number of cells) In the middle of the 1960s, it was reported that Megestrol acetate was effective in the treatment of endometrial hyperplasia.

It was first looked at as a way to treat endometrial cancer in 1967, and the results were published in 1973. Megestrol Acetate was reportedly introduced for the treatment of endometrial cancer in the United States in 1971. In 1951 and 1952, progesterone was studied as a way to treat breast cancer, but the results were not very impressive. In 1967, Megestrol Acetate was one of the first progestins to be looked at for treating breast cancer. A second study was conducted in 1974. When a study was published in 1978 that used a large dose of medroxyprogesterone acetate to treat breast cancer, it was seen as a "breakthrough" and sparked a lot of interest in progestins as a way to treat breast cancer. In 1980, a third study of Megestrol Acetate for breast cancer was published, and more studies were done in the 1980s and after. At least by 1983, Megestrol Acetae was approved for treating breast cancer in the United States.

In the 1980s, clinical studies of very high doses of Megestrol Acetate for breast cancer showed that patients gained a lot of weight and ate more, even though they had advanced cancer. This made Researcher think that Megestrol Acetate might be a good way to make people eat more. In 1986, a paper was published suggesting that Megestrol Acetate be studied and maybe used to treat cachexia.(Cachexia is a complicated syndrome caused by an underlying illness that leads to a steady loss of muscle that can't be completely stopped by taking nutritional supplements).

Megestrol Acetate was then looked at for this indication, and after phase III clinical trials were done, it was approved in the United States in 1993 as an oral suspension to treat anorexia–cachexia syndrome caused by cancer and other long-term conditions like HIV/AIDS. Since then, the company that makes Megace ES, Par Pharmaceutical(Endo International Company), has heavily promoted it as a way to treat unintentional weight loss in older people, especially those who live in long-term care facilities. In March 2013, Par Pharmaceutical settled a federal and multi-state criminal and civil lawsuit for $45 million. The company was accused of pushing the branded version of MGA over the generic version to treat geriatric wasting that wasn't caused by AIDS or Cancer.

Study revealed that Megestrol Acetate combined with ONS may be an effective and safe treatment option for lung cancer-related malnutrition.

Megestrol Acetate drug used in tablet form to relieve the symptoms of advanced breast cancer and endometrial cancer. It is also being studied in the treatment of other conditions and types of cancer. Megestrol acetate blocks the effects of the hormone estrogen in the body, which may help keep some cancer cells from growing. It is a type of progestin.


The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature. Nonetheless, based primarily on the cost and inconvenience associated with the use of higher doses of this drug, it is reasonable to use 160 mg/d for the initial treatment of cancer anorexia/cachexia in routine clinical practice.

Primary hormonal therapy of advanced breast cancer with megestrol acetate: predictive value of estrogen receptor and progesterone receptor levels.