Expert Opinion on Pharmacotherapy最新文献

Introduction: Endometriosis is a chronic inflammatory estrogen-dependent disease affecting 10% of women worldwide leading to chronic pelvic pain and infertility which may be treated clinically or surgically.

Areas covered: Current literaure was reviewed using the keywords 'gonadotropin releasing hormone agonists (GnRHa),' 'endometriosis,' 'infertility' and 'chronic pelvic pain.' Relevant papers prioritizing randomized controlled clinical trials (RCT), systematic reviews, meta-analyses, as well as international guidelines were evaluated.

Expert opinion: Available options for relieving endometriosis associated pain include GnRHa, progestagens and combined oral contraceptives all of which block menstruation to control symptoms without curing the disease. GnRHa administration decreases pain and symptom recurrency after surgical treatment but side effects and costs limit its use. Published studies to test its effectiveness in easing endometriosis associated pain are heterogeneous, consider different outcomes with no long term results. Drug choice should be individualized considering the side-effects profile, tolerability, costs, risks and benefits as one size does not fit all. As we wait for the development of an ideal pharmacological agente, GnRHa with an add-back regimen remain a second line option to alleviate the painful symptoms in women with endometriosis. Endometriosis management should consider the systemic nature of the disease and the complexity involved in the pathogenesis of symptoms.

Introduction: . The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role in treatment resistance. This pathway's involvement in breast carcinogenesis and its link to treatment resistance underscores the significance of targeting it in BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due to toxicity issues that hinder their development.

Areas covered: This review discusses the PI3K-pathway inhibitors used in BC, highlighting emerging, innovative strategies.

Expert opinion: The introduction of mTOR inhibitors marked a key step in tackling hormone receptor-positive (HR+) BC, targeting endocrine resistance. However, toxicity concerns remain, especially with PIK3CA and AKT inhibitors. Selective PI3K-targeted agents aim to reduce off-target toxicity, enhancing patient adherence and control over the disease. New compounds employing allosteric mechanisms may further limit adverse effects and allow safer combination therapies, previously limited by toxicity. Advancements in dosing strategies, focus on patient-centered outcomes, and synergistic agents are essential in advancing AKT-pathway inhibition, paving the way for a new phase in HR+ BC treatment.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) and its associated pain negatively affect patient outcomes and quality of life (QoL). The two-part MiroCIP study included interventional and prospective observational studies. Here, we report the latter, describing CIPN incidence, risk factors, and outcomes.

Research design and methods: This 1-year, multicenter, prospective registry study (May 2021-April 2023) included patients aged ≥20 years with colorectal, gastric, non-small cell lung, or breast cancer who were scheduled to undergo chemotherapy with oxaliplatin or taxane. The primary endpoint was Grade ≥ 2 sensory CIPN incidence within 12 months after chemotherapy initiation. Subjective and objective symptoms, QoL, and pain were evaluated.

Results: Overall, 216 patients (female, 64.4%; mean age, 60.3 years) were included. Ninety-one (42.1%) and 131 (60.6%) patients received oxaliplatin- and taxane-based chemotherapy, respectively (six received both and were included in both groups). Grade ≥ 2 CIPN occurred in 96 patients (44.4%; 72.8/100 person-years), with 70.8% (68/96 patients) developing symptoms within 90 days. The most prominent CIPN symptoms were limb numbness/tingling and decreased vibration sensibility. No clinically meaningful risk factors were identified.

Conclusions: We clarified CIPN incidence in cancer patients. Subjective symptoms (limb numbness/tingling, decreased vibration sensibility) and pain are important CIPN symptoms requiring careful monitoring.

Trial registration: jRCTs031210101.

Introduction: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A. Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist.

Areas covered: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts.

Expert opinion: While post hoc analyses indicate that palovarotene may have modest benefits for the inhibition of new HO formation in FOP, a number of limitations and concerns remain about its generalized use. Although the long-term risks and benefits of treatment with palovarotene remain unknown, the regional approval of palovarotene marks a milestone for the FOP community at the very beginning of a new era of clinical trials.

Introduction: Dysmenorrhea is a painful symptom associated with uterine contractions and menstrual bleeding and is treated by administering analgesic drugs. Since progesterone receptors (PRs) have a major role in regulating uterine tissues (myometrium and endometrium) physiology, oral contraceptives are used off-label for treating primary or secondary dysmenorrhea. The development of selective progesterone receptor modulators (SPRMs), a class of synthetic steroids with agonistic, antagonistic, or mixed effects in targeting PRs in different tissues, stimulated their possible clinical use for treating secondary dysmenorrhea related to uterine diseases (endometriosis, adenomyosis, uterine fibroids).

Areas covered: The present review examines the development of the clinical trials and observational studies done with the different SPRMs for the treatment of dysmenorrhea in patients with uterine diseases.

Expert opinion: Mifepristone, telapristone acetate and vilaprisan have antagonistic activity on PRs, whereas ulipristal acetate and asoprisnil have both potent antagonist and partial agonist effects.Since no studies have been done on primary dysmenorrhea, the different SPRMs have been evaluated in the treatment of endometriosis, adenomyosis and uterine fibroid-related dysmenorrhea.

Introduction: Osteoporosis is a metabolic skeletal disease characterized by low bone mass and strength, and increased risk for fragility fractures. It is a major health issue in aging populations, due to fracture-associated increased disability and mortality. Antiresorptive treatments are first line choices in most of the cases.

Areas covered: Bone homeostasis is complicated, and multiple factors can compromise skeletal health. Bone turnover is a continuous process regulated by the coupled activities of bone cells that preserves skeletal strength and integrity. Imbalance between bone resorption and formation leads to bone loss and increased susceptibility to fractures. Antiresorptives prevent bone loss and reduce fracture risk, by targeting osteoclastogenesis and osteoclast function and survival. Their major drawback is the coupling of osteoclast and osteoblast activity, due to which any reduction in bone resorption is followed by suppression of bone formation.

Expert opinion: During the last couple of decades significant progress has been made in understanding of the genetic and molecular basis of osteoporosis. Critical pathways and key molecules that mediate regulation of bone resorption have been identified. These factors may underpin novel therapeutic avenues for osteoporosis, but their potential for translation into clinical applications is yet to be tested.

Introduction: BPH/male LUTS is a prevalent condition in the aging male population with multifactorial pathophysiology. Pharmacotherapy remains the cornerstone of treatment in patients who fail conservative treatment. 5-α-Reductase inhibitors (5-ARIs) are the only class of medication shown to reduce the risk of acute retention and BPH-related surgery and, thus, are commonly used along with other "short acting" medications in combination treatments.

Areas covered: Combination treatments with α-blockers and 5-ARIs have been investigated extensively in high quality trials that prove the long-term efficacy of such treatments with acceptable rates of side effects. Combination treatments involving 5-ARIs and other classes of medications (anticholinergics, b3 agonists, PDEI) have been shown to be beneficial in the short term and but studies with longer follow-up periods are required to fully establish their role.

Expert opinion: A-blocker/5-ARI combination treatment is a reasonable approach for patients with male LUTS/BPH who are at increased risk of disease progression or have incomplete response to monotherapies. Other combination treatments with 5-ARIs and PDEI or anticholinergics/β-3 agonists can be tried based on predominant symptoms or side effect profile, but patients should be informed about the lack of long-term data.