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Acromegaly
Published in Nadia Barghouthi, Jessica Perini, Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
For patients considering breastfeeding, concurrent medical management of acromegaly is controversial as there are limited data. Dopamine agonists are incompatible with breastfeeding as they inhibit lactation.22,23Octreotide is excreted into breast milk; however, absorption from the oral route is unknown.6Pasireotide and lanreotide both pass into the milk of lactating rats.24,25 Due to the potential presence in human milk and the prolonged half-life of pasireotide, it is recommended to avoid breastfeeding for 6 months after pasireotide is discontinued.25 In a single patient, the levels of pegvisomant in the breast milk were below the lower limit of quantification of the assay.26
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Pasireotide (as the SigniforTM brand) is available as both a solution of the disparate salt for injection, and a pamoate salt in powder form for reconstitution for injection. A depot version, Pasireotide LARTM, was approved by the FDA and EU for the treatment of acromegaly in 2014. The side effects of pasireotide are similar to those of octreotide and lanreotide, and the manufacturers advise that it should be used with caution in patients with diabetes mellitus, liver disease, and cardiac disorders (including bradycardia). It should not be used in pregnancy or while breastfeeding, and the use of contraception is advised throughout treatment due to a possible teratogenic affect.
Endocrine and Neuroendocrine Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Natasha Shrikrishnapalasuriyar, P.N. Plowman, Márta Korbonits, Ashley B. Grossman
Medical treatment is recommended for patients who decline surgery, are unfit, or despite surgery have active disease. First-line medical treatment is the use of somatostatin receptor ligands (SRL), with cabergoline and GH receptor antagonists held in reserve for treatment failure. SRLs are effective in controlling GH/IGF-1 hypersecretion and reduce tumor size, but are completely effective in hormonal control in only around 30% of patients. Octreotide LAR and Lanreotide Autogel are the SRLs in general use, activating the somatostatin receptor subtype 2, while second generation somatostatin analogues include pasireotide, which acts on the subtype 5 receptor (amongst others) and may be considered in cases of resistance to octreotide or lanreotide. However, nearly 70% of patients develop impaired glycemic control with pasireotide, which needs to be taken into consideration, especially in patients with pre-existing diabetes.35 The dopamine agonist cabergoline can be used in conjunction with first-line somatostatin analogues in patients who have mildly elevated IGF-1 at baseline, but is of limited efficacy.
New insights into targeting hepatic cystogenesis in autosomal dominant polycystic liver and kidney disease
Published in Expert Opinion on Therapeutic Targets, 2020
Thijs R. M. Barten, Lucas H. P. Bernts, Joost P. H. Drenth, Tom J. G. Gevers
Another important approach to improve outcomes is by combining different therapeutic targets to create a synergistic effect. We have already shown in this review that combining different treatment modalities (octreotide and pasireotide) can reduce side effects while maintaining efficacy [34]. Similarly, a study with Pkd1 mice showed that concomitant administration of tolvaptan and pasireotide reduced cystic volumes and decreased cAMP to wild-type levels [87]. Both studies aimed to reduce cyst growth by simultaneous administration of drugs that target the cAMP pathway. A synergistic effect could further be enhanced when combining treatments that target distinct pathways, as demonstrated by a study that combined hydroxychloroquine and pasireotide in PCK rats and found that the combination achieved better repression of cystogenesis compared to each drug alone [64]. We believe that when targeting the female hormone pathway appears effective, combining this strategy with SAs is a key strategy that could provide a viable treatment option in PLD.
New and emerging systemic therapy options for well-differentiated gastroenteropancreatic neuroendocrine tumors
Published in Expert Opinion on Pharmacotherapy, 2020
Steven D. Scoville, Jordan M. Cloyd, Timothy M. Pawlik
Recent research has investigated the efficacy of other SSAs. For example, pasireotide is a newer SSA with higher affinity for SSTRs 1, 2, 3, and 5, compared to octreotide and lanreotide which primarily target SSTR2. Pasireotide had previously been used for postoperative pancreatic fistula prevention and treatment of pituitary tumors [25,26]. Early studies had suggested pasireotide may be an effective alternative for tumors that had become resistant to octreotide or lanreotide [27,28]. However, a randomized phase III trial comparing pasireotide to octreotide LAR was stopped early due to a lack of difference in symptom control despite initial PFS improvements noted in the pasireotide treatment arm [29]. Several other monotherapy, combination, or increased dosage treatment strategies with pasireotide are currently being explored [30]. Pasireotide has not been approved for use in GEP-NETs but is certainly a focus of future research efforts.
The emerging role of targeted therapies for advanced well-differentiated gastroenteropancreatic neuroendocrine tumors
Published in Expert Review of Clinical Pharmacology, 2019
Jordan M. Cloyd, Bhavana Konda, Manisha H. Shah, Timothy M. Pawlik
While not approved for use in GEP-NETs, other SSAs have been studied. For example, pasireotide, which binds to SSTR subtypes 1,2,3, and 5, was reported in an early preliminary trial to have promising efficacy for advanced NETs refractory to standard SSAs [24]. A randomized phase 3 trial comparing pasireotide to octreotide LAR was stopped early based on non-inferiority of differences in symptom control. However, at the early stopping point, PFS was improved among patients receiving pasireotide compared with octreotide LAR [25]. Multiple other single arm and randomized clinical trials have explored the use of pasireotide either as monotherapy or in combination with other drugs (e.g. everolimus, cabergoline, teriflunomide) to treat NETs [26]. However, given the increased side effect profile, and lack of convincing evidence of increased antitumor efficacy, pasireotide is not currently approved for use in GEP-NETs. Regardless of the specific agent, given the low objective response rate observed, patients with indolent, low-volume disease and low proliferative rate histology are presumably the best candidates for SSA therapy. SSAs may also be used as a bridge to more effective systemic therapies when the rate of disease progression begins to increase.