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Cancer Control : Journal of the Moffitt... Apr 2016A man aged 65 years with metastatic renal cell carcinoma presented for evaluation after a recent fall. A thorough workup of the case was performed and secondary adrenal...
A man aged 65 years with metastatic renal cell carcinoma presented for evaluation after a recent fall. A thorough workup of the case was performed and secondary adrenal insufficiency induced by the administration of megestrol acetate was determined to be the cause. Adrenal insufficiency is a serious disorder that is a potential adverse event of megestrol acetate, a medication used to help patients with cancer cachexia increase their appetite and gain weight. This association is not well recognized in clinical practice, so this case highlights the importance of distinguishing possible endocrine complications induced by the long-term administration or sudden discontinuation of megestrol acetate.
Topics: Adrenal Insufficiency; Aged; Humans; Male; Megestrol Acetate
PubMed: 27218795
DOI: 10.1177/107327481602300212 -
Supportive Care in Cancer : Official... Aug 2015Delayed chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of moderately emetogenic chemotherapy not containing anthracyclines and... (Review)
Review
Prophylactic treatment for delayed chemotherapy-induced nausea and vomiting after non-AC based moderately emetogenic chemotherapy: a systematic review of randomized controlled trials.
PURPOSE
Delayed chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of moderately emetogenic chemotherapy not containing anthracyclines and cyclophosphamide (non-AC MEC). In this review, we summarize current literature to update recommendations for delayed CINV prophylaxis after non-AC MEC.
METHODS
We conducted a systematic search in PubMed and conference proceedings from ASCO, ESMO, and MASCC. Included randomized controlled trials (RCTs) aimed to prospectively evaluate the efficacy of two or more antiemetic strategies in the prevention of delayed CINV after the administration of non-AC MEC. At least one of the following endpoints was used: complete response, complete control, no nausea, no vomiting, and/or no use of rescue medication.
RESULTS
Our search provided 247 publications. Nine met the predefined criteria. Included RCTs reported outcomes on palonosetron, aprepitant, casopitant, netupitant/palonosetron (NEPA), olanzapine, and megestrol acetate.
CONCLUSIONS
Superiority of palonosetron over first-generation 5-HT3 receptor antagonists for the prevention of acute and delayed CINV after non-AC MEC has not been proven. The addition of an NK1 receptor antagonist to first-generation 5-HT3 receptor antagonists does not significantly improve the incidence of delayed CINV after non-AC MEC. The efficacy of a single-day regimen of dexamethasone with palonosetron is non-inferior to multiday dexamethasone. NEPA, olanzapine, and megestrol acetate show highly effective complete response (CR) rates.
Topics: Antiemetics; Antineoplastic Agents; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Nausea; Vomiting
PubMed: 26041480
DOI: 10.1007/s00520-015-2778-6 -
World Journal of Gastroenterology Mar 2008Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced... (Review)
Review
Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Sex hormones receptors are expressed in a significant proportion of HCC samples. Following preclinical and epidemiological studies supporting a relationship between sex hormones and HCC tumorigenesis, several randomized controlled trials (RCTs) tested the efficacy of the anti-estrogen tamoxifen as systemic treatment. Largest among these trials showed no survival advantage from the administration of tamoxifen, and the recent Cochrane systematic review produced a completely negative result. This questions the relevance of estrogen receptor-mediated pathways in HCC. However, a possible explanation for these disappointing results is the lack of proper patients selection according to sex hormones receptors expression, but unfortunately the interaction between this expression and efficacy of tamoxifen has not been studied adequately. It has been also proposed that negative results might be explained if tamoxifen acts in HCC via an estrogen receptor-independent pathway, that requires higher doses than those usually administered, but an Asian RCT conducted to assess dose-response effect was completely negative. Interesting, preliminary results have been obtained when hormonal treatment (tamoxifen or megestrol) has been selected according to the presence of wild-type or variant estrogen receptors respectively, but no large RCTs are available to support this strategy. Negative results have been obtained also with anti-androgen therapy. In conclusion, there is no robust evidence to consider HCC a hormone-responsive tumor. Hormonal treatments should not be part of the current management of HCC.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Evidence-Based Medicine; Gonadal Steroid Hormones; Humans; Liver Neoplasms; Megestrol Acetate; Meta-Analysis as Topic; Neoplasms, Hormone-Dependent; Patient Selection; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Receptors, Steroid; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome
PubMed: 18350599
DOI: 10.3748/wjg.14.1682 -
Annals of Oncology : Official Journal... Jul 2003Advanced breast cancer is largely incurable and current treatment modalities are aimed towards restricting tumour growth, prolonging survival, palliating symptoms and... (Review)
Review
BACKGROUND
Advanced breast cancer is largely incurable and current treatment modalities are aimed towards restricting tumour growth, prolonging survival, palliating symptoms and maintaining quality of life (QoL). The development of breast cancer is strongly influenced by endogenous oestrogens (and other growth factors), leading to a strong focus on the development of antioestrogenic compounds for the treatment of hormone-sensitive advanced disease.
DESIGN
This is a review of current endocrine therapies available for postmenopausal women with advanced breast cancer, examining the likely impact of newer agents on treatment strategies.
RESULTS
In postmenopausal women, current treatment options include tamoxifen, aromatase inhibitors (AIs) and megestrol acetate. Fulvestrant ('Faslodex') is a new, well-tolerated, oestrogen receptor antagonist that has no known agonist effect and is at least as effective as the AI anastrozole for the treatment of postmenopausal patients with metastatic or advanced breast cancer who have progressed on prior endocrine therapy. Fulvestrant maintains QoL throughout successful treatment.
CONCLUSIONS
Fulvestrant represents a new treatment option for postmenopausal women with advanced disease. New agents that appear to lack cross-resistance with existing treatments may be used to extend the time period during which endocrine therapy may be employed before the need for cytotoxic chemotherapy.
Topics: Aged; Aromatase Inhibitors; Breast Neoplasms; Down-Regulation; Enzyme Inhibitors; Estradiol; Estrogen Antagonists; Female; Fulvestrant; Humans; Megestrol Acetate; Middle Aged; Postmenopause; Prognosis; Quality of Life; Receptors, Estrogen; Tamoxifen
PubMed: 12853342
DOI: 10.1093/annonc/mdg290 -
The Cochrane Database of Systematic... Jan 2007Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use for many years. Aromatase inhibitors (AIs) are a class of compounds that systemically inhibit oestrogen synthesis in the peripheral tissues. Aminoglutethimide was the first AI in clinical use (first generation) and had a similar tumour-regressing effect to other endocrine treatments, which showed the potential of this alternative type of therapy. Other AIs have since been developed and the third generation AIs anastrozole, exemestane and letrozole are in current use. Randomised evidence on response rates and side effects of these drugs is still limited.
OBJECTIVES
To compare aromatase inhibitors to other endocrine therapy in the treatment of advanced breast cancer in postmenopausal women.
SEARCH STRATEGY
The Cochrane Breast Cancer Group Specialised Register was searched on 3 December 2004 using the codes for "advanced" and "endocrine therapy". Details of the search strategy applied to create the Register and the procedure used to code references are described in the Cochrane Breast Cancer Group module on The Cochrane Library. The search was updated to 30 September 2005 and additional publications were included. Experts were consulted to determine that no relevant studies had been excluded.
SELECTION CRITERIA
Randomised trials comparing the effects of any aromatase inhibitor versus other endocrine therapy, no endocrine therapy or a different aromatase inhibitor in the treatment of advanced (metastatic) breast cancer.
DATA COLLECTION AND ANALYSIS
Data from published trials were extracted by two independent review authors. A third independent author then carried out a further cross check for accuracy and consistency. Hazard ratios (HR) were derived for analysis of time-to-event outcomes (overall and progression-free). Odds ratios (OR) were derived for objective response and clinical benefit (both analysed as dichotomous variables). Toxicity data were extracted where present and treatments were compared using odds ratios. All but one of the studies included data on one or more of the following outcomes: overall survival, progression-free survival, clinical benefit and objective response.
MAIN RESULTS
Thirty studies were identified, twenty five of which were included in the main analysis of any AI versus any other treatment (9416 women). The pooled estimate showed a significant survival benefit for treatment with an AI over other endocrine therapies (HR 0.89, 95%CI 0.82 to 0.96). A subgroup analysis of the three commonly prescribed AIs (anastrozole, exemestane, letrozole) also showed a similar survival benefit (HR 0.88, 95%CI 0.80 to 0.96). The results for progression-free survival, clinical benefit and objective response were not statistically significant and there was statistically significant heterogeneity across types of AI. There were very limited data to compare one AI with a different AI, but these suggested an advantage for letrozole over anastrozole. All the trials of AIs used exclusively as first-line therapy were against tamoxifen. There was an advantage to treatment with AIs in terms of progression-free survival (HR 0.78, 95% CI 0.70 to 0.86) and clinical benefit (OR 0.70, 95% CI 0.51 to 0.97) but not overall survival or objective response. There was considerable heterogeneity across studies when considering clinical benefit (P = 0.001). Use of an AI as second-line therapy showed a significant benefit in terms of overall survival (HR 0.80, 95% CI 0.66 to 0.96) but not for progression-free survival (HR 1.08, 95% CI 0.89 to 1.31), clinical benefit (OR 1.00, 95% CI 0.87 to 1.14) or objective response (OR 0.96, 95% CI 0.81 to 1.14). This is difficult to interpret due to the extreme heterogeneity across AIs for progression-free survival but not the other endpoints.AIs have a different toxicity profile to other endocrine therapies. For all AIs combined, they had similar levels of hot flushes (especially when compared to tamoxifen) and arthralgia, increased risks of nausea, diarrhoea and vomiting, but a decreased risk of vaginal bleeding and thromboembolic events compared with other endocrine therapies. A similar pattern of risks and benefits was still seen when analyses were limited to the currently most-prescribed third generation AIs.
AUTHORS' CONCLUSIONS
In women with advanced (metastatic) breast cancer, aromatase inhibitors including those in current clinical use show a survival benefit when compared to other endocrine therapy.
Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Female; Humans; Neoplasms, Hormone-Dependent; Randomized Controlled Trials as Topic
PubMed: 17253488
DOI: 10.1002/14651858.CD003370.pub2 -
Frontiers in Oncology 2022The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients...
BACKGROUND
The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins.
STUDY DESIGN
Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA".
RESULTS
A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months.
CONCLUSIONS
Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.
PubMed: 36185260
DOI: 10.3389/fonc.2022.965029 -
International Journal of Molecular... Oct 2021Endometrial cancer (EC) is a deleterious condition which strongly affects a woman's quality of life. Although aggressive interventions should be considered to treat... (Review)
Review
Endometrial cancer (EC) is a deleterious condition which strongly affects a woman's quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.
Topics: Adult; Endometrial Neoplasms; Female; Fertility; Fertility Preservation; Humans; Medroxyprogesterone Acetate; Myometrium; Neoplasm Staging; Progestins; Quality of Life
PubMed: 34769256
DOI: 10.3390/ijms222111825 -
Journal of B.U.ON. : Official Journal... 2021To explore the clinical efficacy of hysteroscopic resection combined with megestrol acetate in the treatment of patients with early-stage endometrial cancer (EC) and its...
PURPOSE
To explore the clinical efficacy of hysteroscopic resection combined with megestrol acetate in the treatment of patients with early-stage endometrial cancer (EC) and its prognosis.
METHODS
130 patients with early-stage EC were divided into two groups: MA group (hysteroscopic resection combined with megestrol acetate, n=65) and Control group (hysteroscopic resection alone, n=65). The clinical efficacy, serum carbohydrate antigen 125 (CA125) level and incidence of adverse reactions were compared between the two groups, and the patients' pregnancy status, pregnancy outcome, survival status and tumor recurrence were recorded through follow-up.
RESULTS
The curative effect was assessed in all patients after treatment. The overall response rate was 83.1% (54/65) and 65.2% (43/65), respectively, in MA group and Control group, which was significant better in MA group than that in Control group. After treatment, the serum CA125 levels markedly declined in both groups. The pregnancy rate in MA group was obviously higher than in Control group. The follow-up results revealed that the 5-year overall survival (OS) was 83.1% (54/65) and 81.5% (53/65) and the progression-free survival (PFS) was 76.9% (50/65) and 73.8% (48/65), respectively, in MA group and Control group.
CONCLUSION
Hysteroscopic resection combined with megestrol acetate has superior clinical efficacy to hysteroscopic resection alone in the treatment of patients with early-stage EC, which can greatly increase the success rate of pregnancy and reduce the serum CA125 level. However, thelong-term survival and PFS of patients had no significant differencesbetween the two treatment methods. Key words: hysteroscopic resection, megestrol acetate, endometrial cancer, early stage, curative effect.
Topics: Adult; Antineoplastic Agents, Hormonal; Carcinoma, Endometrioid; Combined Modality Therapy; Endometrial Neoplasms; Female; Humans; Hysteroscopy; Megestrol Acetate; Neoplasm Staging; Progesterone; Prognosis; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 34564987
DOI: No ID Found -
Current Problems in Cancer 2011Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and...
Cancer-induced cachexia remains a significant cause of morbidity and mortality in cancer treatment. Cancer research and development continues at an aggressive pace and yet a degree of cancer-induced cachexia is experienced by up to 80% of advanced stage cancer patients. Unfortunately, there are no established treatment regimens for this condition. Weight loss and fatigue consistently appear in patient oncologic histories and progress notes. However, few oncologists fully understand the pathologic mechanisms causing cachexia resulting in well-meaning advice to increase caloric intake with minimal results. Our goal is to describe the pathologic basis of cancer-induced cachexia and to detail accompanying metabolic derangements. Understanding the causes of cachexia sheds light on the subsequent need for multi-modality therapy including clinical intervention with specialized nutrition support, drug therapy, lifestyle and diet changes. In addition to nutrition support modalities, practicing oncologists may prescribe medical therapies designed to increase body weight and lean body mass, including megestrol acetate, tetrahydrocannibinol, oxandrolone, and non-steroidal anti-inflammatory drugs. A variety of experimental therapies are also being investigated for cancer-induced cachexia including tumor necrosis factor-alpha inhibitors and ghrelin infusions. We review the available data to support nutrition-oriented interventions in cancer-induced cachexia, including omega-3 fatty acids, amino-acid loading/protein supplementation, parenteral and enteral nutrition support, and food-derived compounds such as curcumin, reservatrol, and pomegranate.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Curcumin; Dronabinol; Fatty Acids, Omega-3; Ghrelin; Humans; Interleukins; Lythraceae; Megestrol Acetate; NF-kappa B; Neoplasms; Nutrition Assessment; Nutritional Physiological Phenomena; Nutritional Requirements; Nutritional Support; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha
PubMed: 21420558
DOI: 10.1016/j.currproblcancer.2011.01.001 -
Experimental and Therapeutic Medicine Jan 2023Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are...
Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are limited therapeutic options for this syndrome. Previous evidence has demonstrated that increasing adipose tissue may improve quality of life and survival outcomes in cachexia. Cisplatin, as a chemotherapy drug, also causes cachexia during antitumor therapy due to its adverse effects. To establish a rat model of cachexia, the animals were intraperitoneally treated with cisplatin at doses of 1, 2 and 3 mg/kg, and the rats that responded to cisplatin at the optimal dose were used to test the effect of nomegestrol acetate (NOMAc). Rats that were assessed to be sensitive to cisplatin were randomly grouped and intragastrically administered vehicle, 5 or 10 mg/kg megestrol acetate (MA) or 2.5, 5 or 10 mg/kg NOMAc. The body weights and food consumption of the rats were assessed. Serum IL-6 and TNF-α levels were assessed using ELISA. The protein expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), peroxisome proliferator activated receptor γ (PPARγ), fatty acid synthase (FASN) and sterol regulatory element-binding protein-1 (SREBP-1) from inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) were evaluated using western blotting. The optimal way to establish a chemotherapy-induced rat model of cachexia demonstrated in the present study was to intraperitoneally administer the rats with 2 mg/kg cisplatin for 3 consecutive days. NOMAc (2.5, 5 mg/kg) and MA (10 mg/kg) were able to significantly ameliorate the loss of body weight in the cisplatin-induced cachectic rats. NOMAc significantly reduced the serum levels of TNF-α at 10 mg/kg. Morphologically, iWAT atrophy, with a remarkable reduction in adipocyte volume, was observed in the cisplatin-induced cachectic rats, but the effects were reversed by administering 5, 10 mg/kg NOMAc or 10 mg/kg MA. Furthermore, 2.5 mg/kg NOMAc markedly reduced the protein expression levels of the lipolysis genes HSL and ATGL, and 5 mg/kg NOMAc markedly enhanced the protein expression levels of adipogenesis genes, including FASN, SREBP-1 and PPARγ in iWAT but not in eWAT. NOMAc was demonstrated to improve cachexia at lower doses compared with MA. Overall, NOMAc is likely to be a promising candidate drug for ameliorating cancer cachexia induced by cisplatin.
PubMed: 36561625
DOI: 10.3892/etm.2022.11723