Efficacy Of Octreotide LAR Research Articles

Efficacy of long-acting release octreotide for preventing chemotherapy-induced diarrhoea: protocol for a systematic review

IntroductionDiarrhoea is a common adverse effect induced by chemotherapy that can reduce the dose of chemotherapeutic drugs or interrupt the chemotherapy schedule. The current treatment strategies have various limitations. It...

Long-term efficacy of octreotide LAR in acromegaly patients, a prospective single centre study with 7 years follow up

Long-term efficacy of octreotide LAR in acromegaly patients, a prospective single centre study with 7 years follow up

Efficacy of octreotide LAR (OCT) in patients (pts) with advanced neuroendocrine tumors (NET): A post hoc analysis of the placebo (PBO) arm of the phase III RADIANT-2 study with updated survival data.

265 Background: In pts with metastatic midgut NET, OCT showed antitumor activity and significantly extended time to tumor progression (TTP) vs PBO (PROMID trial, Rinke et al. 2009). We present a post hoc analysis assessing efficacy of OCT (30 mg q28d) in the PBO+ OCT arm of the phase III RADIANT-2 study. Methods: For this post hoc analysis, progression-free survival (PFS by central review, cutoff Apr 2, 2010) and overall survival (OS, cutoff Jun 13, 2013) in the PBO + OCT arm were estimated by prior somatostatin analogue (SSA) use and primary tumor location subgroups using the Kaplan-Meier (KM) method. Results: 213 pts were randomized to PBO + OCT (median age, 60 yrs; male, 58%; WHO PS: 0/1/2 in 66%/29%/5% pts; >80% had well-differentiated disease). Of these, 47 (22%) were SSA naïve (foregut, 32%; midgut, 51%; hindgut, 4%; not classified or missing, 13%) and 166 (78%) had received SSA (foregut, 10%; midgut, 72%; hindgut, 11%; not classified or missing, 7%) prior to study entry. Median PFS (95% CI) for pts who were SSA naïve vs who had received SSA was 13.6 (8.2-22.7) mos vs 11.1 (8.4-14.2) mos. By primary tumor location, median PFS (95% CI) in SSA naïve pts vs who received SSA was 5.7 (2.8-27.8) mos vs 8.7 (2.8-13.9) mos for foregut, 22.2 (8.3-29.5) mos vs 12.0 (8.4-17.7) mos for midgut, and not-reached (NR; 4.7-NR) vs 6.6 (3.0-13.0) mos for hindgut. OS analysis is in table. Conclusions: This post hoc analysis of the PBO + OCT arm of the RADIANT-2 study showed a PFS of 13.6 mos in SSA naïve pts treated with OCT. While the RADIANT-2 study PBO arm differs from PROMID in patient population and method of assessment of tumor progression, the data from this post hoc analysis provide additional evidence of the antiproliferative effect of OCT in NET. Clinical trial information: NCT00412061. [Table: see text]

Neoadjuvant treatment of primary inoperable or local recurrent thymoma with octreotide LAR to improve tumor resectability.

7105 Background: The therapeutic outcome for unresectable, locally advanced, malignant thymoma is poor. Most important factor for long-term survival in thymoma patients is complete resection (R0) of the tumor. The study was performed to evaluate the efficacy of octreotide LAR plus prednisone in patients with primary inoperable or local recurrent thymoma to reduce tumor size. Methods: This was an open label, single-arm study in patients with inoperable or local recurrent thymoma. Patients were considered unlikely to achieve R0 resection at enrollment. Octreotide LAR was administered once every 2 weeks in combination with prednisone. Two stages were planned according to Fleming’s one sample multiple testing procedure for phase II clinical trials. The objective of the study was to show that octreotide LAR is effective in this patient population with respect to tumor shrinkage. Response was defined as decrease in tumor volume of at least 20% at month 3 as compared to baseline. Results: 17 thymoma patients at Masaoka stage III were recruited. Octreotide LAR showed a response in 15 of 17 patients (88.24%) at week 12. Two patients had discontinued the study before week 12 due to unsatisfactory therapeutic effect or adverse events. At Week 12, 5 patients (29.41%) operable for radical resection. 10 patients (58.82%) were not operable for radical resection. 16 of 17 patients (94.12%) experienced adverse events (AEs). The most frequent AEs were gastrointestinal disorders (70.59%), infections and infestations (64.71%), and blood/lymphatic system disorders (41.18%). Conclusions: Octreotide LAR was shown to be effective in patients with inoperable thymoma with respect to tumor shrinkage.Octreotide LAR was generally well tolerated. The reported AEs are in accordance with the known safety profile.

The efficacy of octreotide LAR in acromegalic patients as primary or secondary therapy

The objective of this study was to investigate the efficacy of octreotide therapy in acromegalic patients as primary or secondary therapy. Ten acromegalic patients diagnosed at the Endocrinology Clinic in Sarajevo (seven females and three males, mean age 55.2 ± 7.2 years, age range 40-65 years, five patients with microadenoma and five patients with macroadenoma) were treated with octreotide. Among them, 60% of patients were operated on and the majority of the procedures were performed transnasaly (90%). That group of patients had recidivism of disease (pituitary adenoma and acromegaly). The concentration of human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1) was evaluated at 0, 6 and 12 months, while magnetic resonance imaging (MRI) was taken before the treatment and 12 months after. Eight patients received octreotide 30 mg/28 days, one patient received a dose of 20 mg and the other received 60 mg/28 days. Before treatment growth hormone (GH) levels were 50.87 ± 10.56 ng/ml (range: 26-64.9), IGF-1 were 776.66 ± 118.40 ng/ml (range: 526-934). Four patients (40%) were treated with primary octreotide treatment and six patients (60%) with secondary somatostatin analog treatment. At the beginning of therapy, there were no differences in terms of age, HGH levels and IGF-1 levels between primary and secondary treatment groups (p > 0.05). The difference between groups was only in regard to the size of tumors (p = 0.01). After 6 and 12 months the GH levels decreased to 1.61 ± 0.86 ng/ml (range: 0.7-2.65) and 1.85 ± 2.40 ng/ml (range: 0.0-8.3), respectively, while the IGF-1 became 305.90 ± 43.19 ng/ml after 6 months of treatment (range: 240-376) and 256.99 ± 71.43 ng/ml after 12 months of octreotide treatment (range: 126-325), respectively. The pituitary adenomas size prior to treatment was 9.57 mm, while after 12 months of treatment, the size decreased to 8.0 mm. After therapy, a GH decrease to less than 2.5 ng/ml was achieved in 90% of cases; tumor size decrease was achieved in 60% while normalization of IGF-1 was achieved in 100% of the patients, respectively. All differences about HGH and IGF-1 in each group were statistically significant (p < 0.05). In the group of acromegalic patients treated with octreotide LAR as primary therapy, the difference was more significant for GH and IGF-1 than for adenomas size. Octreotide treatment of acromegaly not only decreases GH and IGF-1 concentrations, but also appears to diminish the size of the tumor in about 60% of cases. The somatostatin analogs are more efficient in the primary treatment of acromegalic patients, due to the fact that primary therapy is as effective as secondary therapy but primary therapy has small advantages when compared with secondary octreotide therapy because no surgical treatment is required before.

Objective radiological disease control with Sandostatin monotherapy in metastatic neuroendocrine tumours

Conventional cytotoxic chemotherapy is not usually effective in neuroendocrine tumours (NET). Somatostatin analogues (SSA) such as octreotide (Sandostatin; octreotide LAR and lanreotide) are typically used to treat symptoms caused by NET, but not as the primary treatment aiming for an objective response. Recently, results from the PROMID (Placebo-controlled prospective Randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumours) trial were published showing that octreotide LAR significantly lengthens the time to tumour progression compared with a placebo in patients with functionally active and inactive metastatic midgut NET. We report a retrospective descriptive analysis of six patients, treated at two Australian institutions, who obtained an objective radiological tumour response on long acting SSA. In this retrospective series of NET, radiological responses were observed using single agent SSA, which was administered mainly for symptom management. This could be due to an antiproliferative and/or antiangiogenic activity of this agent in NET. A response can occur beyond 12 months, which might explain why the response rate is under reported in NET trials. Further investigation in prospective trials is warranted and the possibility for late responses might have implications for trial design.

The Efficacy of Octreotide LAR as Firstline Therapy for Patients with Newly Diagnosed Acromegaly is Independent of Tumor Extension: Predictive Factors of Tumor and Biochemical Response

Surgical outcome of acromegaly depends on the preoperatory tumor size and extension. Somatostatin analogues are also a highly effective treatment for acromegalic patients. Nevertheless, the response of GH-secreting adenomas to primary medical therapy is variable. The aim of the present study was to evaluate the efficacy of octreotide LAR as primary therapy for acromegalic patients as a function of initial tumor extension. We performed a multicentre, prospective, observational and analytical study recruiting 19 "naive" acromegalic patients (5 microadenomas, 10 intrasellar, and 4 extrasellar macroadenomas). All of them were treated with octreotide LAR for 12 months. Basal GH and fasting IGF-I concentrations, and tumor volume were measured at baseline and after 6 and 12 months of treatment. Six patients withdrew the study. The patients who completed the protocol showed a significant reduction of tumor volume (25+/-23%, Wilk's lambda=0.506, F=4.400, p=0.046) independently of tumor extension at study entry (Wilk's lambda=0.826, F=0.452, p=0.769). A shrinkage >25% of baseline tumor volume was achieved in 8 (42%) patients with no differences between tumor extension subgroups. Basal GH levels (76+/-18%) and fasting IGF-I (52+/-31%) decreased throughout the study. Six (46%) patients normalized their IGF-I levels. Octreotide LAR is an effective first-line treatment for a large group of acromegalic patients independent of initial tumor extension.

Efficacy of Octreotide-LAR in Dieting Women With Abdominal Obesity and Polycystic Ovary Syndrome

Somatostatin, an endogenous hypothalamic peptide, lowers circulating levels of luteinizing hormone (LH), growth hormone, and insulin. The presence of somatostatin receptors at both the ovarian and adrenal levels suggests that somatostatin analogs may be effective as a treatment for polycystic ovary syndrome (PCOS). This study evaluated one of these analogs, octreotide-LAR, a long-acting formulation, versus placebo, in 20 overweight or obese women with PCOS, 18 of whom completed the study. Octreotide has been shown to lower levels of LH, insulin, insulin-like growth factor-I (IGF-I), and androgen. It also has enhanced spontaneous and stimulated ovulation in women with PCOS. The present patients received a low-calorie diet for 1 month, after which 10 mg octreotide-LAR or placebo was injected every 28 days for 6 months. All women complied with treatment and tolerated it well. Body weight, body mass index, and waist circumference decreased, but differences from the placebo patients were not significant. Testosterone and androstenedione levels declined significantly only in actively treated patients. Both fasting and stimulated insulin levels decreased during treatment with octreotide-LAR, whereas levels of IGF-binding protein-2 (IGFBP-2) and IGFBP-3 increased. Hirsutism improved with active treatment but not in women given placebo. All women given octreotide but only one placebo recipient had ovulated by the end of the trial. Acanthosis nigricans decreased during treatment. Octreotide treatment was associated with significantly higher levels of estradiol and progesterone. One octreotide-treated woman conceived spontaneously in the second cycle after treatment stopped. Long-term benefit is observed in women with PCOS who, in addition to dieting, take octreotide-LAR over the long term. Ovulation is restored to otherwise anovulatory patients. The treatment is well-tolerated and safe.

Efficacy of Octreotide-LAR in Dieting Women with Abdominal Obesity and Polycystic Ovary Syndrome

Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. A single-blind, placebo-controlled study was performed, lasting for 7 months. The patients were ambulatory throughout the study. Twenty PCOS subjects were enrolled. Eighteen completed the study. A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.

Efficacy of Octreotide LAR in Acromegalic Patients

Background: Octreotide (OC)-LAR is a long-acting preparation of octreotide which has been effectively used to suppress GH/IGF-1 hypersecretion in acromegalic patients. The clinical response, biochemical outcomes, and safety of OC-LAR were evaluated in 27 active acromegalic patients. Method: 27 patients with an active disease status (according to the clinical picture, GH >5 μg/L and elevated age-matched IGF-1), and previously treated with bromocriptine after surgery, comprised the study population. OC-LAR was given (20 mg, i.m., every 4 week for 3 injections, then the doses were titrated individually) and the acromegalic symptoms and adverse reactions recorded. The serum levels of GH and IGF-1 were evaluated every 12 week. The acromegalic symptoms including headache, fatigue and arthralgia, improved in all patients. Results: Gastrointestinal side effects were transient and mild. The levels of GH significantly decreased, from 8.9 ± 3.5 to 2.9 ± 2.2 μg/L at 12 weeks (P < 0.001, vs. baseline), to 2.9 ± 2.1 μg/L after 24 weeks (P < 0.001) and to 2.5 ± 1.3 μg/L at 48 weeks (P < 0.001). The levels of IGF-1 significantly decreased, from 753.7 ± 213.6 to 429.7 ± 253.4 μg/L at 12 weeks (P < 0.001, vs. at baseline), to 405.7 ± 213.3 μg/L at 24 weeks (P < 0.001) and to 348.9 ± 144.7 μg/L at 48 weeks (P <0.001). The safelevel of GH is less than 2.5 μg/L and normal age-matched IGF-1 levels were achieved in 63 and 52% of the patients, respectively. Conclusion: Octreotide-LAR was well tolerated and effective as an adjuvant treatment in lowering the levels of GH and IGF-1 in active acromegalic patients (J Kor Soc Endocrinol 20:344～352, 2005).