High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: Clinical and biological effects

Background: Neuroendocrine tumors usually present with inoperable metastatic disease and severe hormonal symtoms. Specific chemotherapy, alpha-interferon and the somatostatin analog octreotide are established therapies in these patients but all of them eventually fail. Other somatostatin analogs, e.g., RC-160 and lanreotide, are currently being studied in different doses and modes of administration.Patients and methods: Nineteen patients with advanced neuroendocrine gastrointestinal tumors [13 carcinoids and six endocrine pancreatic tumors (EPT)], liver metastases being present in 18, most of them heavily pretreated, were included. Seventeen out of 18 patients had somatostatin receptors demonstrated by octreotide scintigraphy. Lanreotide was given as four daily subcutaneous injections, starting with 750 µg/d, then increasing every week up to 12,000 µg/d after six weeks, a dose which was maintained, if tolerated, for 12 months, or until progression.Results: There was a significant tumor size response (>50%) in one patient (5%), whereas 12 patients (70%) had tumor stabilization for 12 months. Bichemical tumor markers were significantly reduced at six months (urinary 5-hydroxyindoleacetic acid and plasma chromogranin) and 12 months (chromogranin) and the overall biochemical response rate was 58% with this high dose of lanreotide. Adverse events were observed and four patients stopped the treatment due to adverse events. Studies of tumor biopsies before and during treatment indicated induction of apoptosis in patients with tumor stabilization and biochemical response.Conclusion: High-dose treatment with lanreotide (12,000 µg/d) produced tumor size response in 5%, stabilization in 70% and a biochemical response in 58% of patients. These results should be related to the advanced stage of the disease as indicated by the mean duration of disease of more than four years, but they do not appear to be better than those achieved with standard doses of somatostatin analogs. However, in responding patients we observed induction of apoptosis in the tumors, a phenomenon not seen with regular doses of somatostatin analogs, but often produced by chemotherapeutic agents.     

Long-acting depot lanreotide in the treatment of patients with advanced neuroendocrine tumors

Long-acting depot forms of somatostatin analogs administered by intramuscular injections are now available for the treatment of neuroendocrine tumors (NETs). In the present study, we investigated the efficacy and tolerability of a slow-release form of lanreotide in patients with advanced NETs. From July 1996 to January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization. All the patients had measurable disease. Seventeen patients were symptomatic and 20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was positive in 23 of 25 patients. Lanreotide was administered as intramuscular injections at the dose of 30 mg every 2 weeks until there was objective, biochemical, or symptomatic tumor progression. Objective partial responses (PRs) were documented in 2 patients (8%), whereas 10 patients (40%) had tumor stabilization. The PRs were observed in patients with midgut carcinoids, of whom one was pretreated with subcutaneous octreotide. The response duration was 21+ and 24+ months in responding patients; the median duration of disease stabilization was 8.5 months (range, 4-21+). The overall biochemical response rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all biochemical responses were observed mostly in patients with carcinoid tumors; the duration of response was 18+ and 30+ months for CRs; the median duration of biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic response rate was 70% with a median duration of 7.5, 18, and 18+ months for diarrhea, abdominal pain, and flushing, respectively. Median duration of lanreotide treatment was 10 months (range, 2-30+). No significant side effects were reported. Depot lanreotide 30 mg shows significant efficacy in terms of objective response rate and in biochemical and symptomatic control, in pretreated patients as well as nonpretreated patients with advanced NETs. Tolerability is good, with good patient compliance.     

Long-term disease stabilization in a patient with castration-resistant metastatic prostate cancer by the addition of lenalidomide to low-dose dexamethasone and celecoxib

Background: Treatment of castrationresistant prostate cancer (CRPC) remains a challenge considering that most patients are elderly men with significant comorbidities. Alternative treatment strategies to cytotoxic therapy should be explored. There is evidence that the continuous administration of cyclooxygenase 2 (COX2) inhibitors and the immunomodulatory agents thalidomide or lenalidomide can result in longterm disease stabilization. Case Report: A 70-year-old patient with castrationresistant metastatic prostate cancer was treated with a combination of lowdose dexamethasone, celecoxib and subsequently lenalidomide. The patient had longterm disease stabilization for 33 months and a very good performance status despite moderate side effects, i.e. moderate Cushing's syndrome and mild laboratory hematologic toxicity. Conclusion: The addition of lenalidomide to low-dose dexamethasone and celecoxib resulted in an impressive longterm disease stabilization of CRPC in this patient, allowing him to lead an active life with a good quality of life.     

Octreotide acetate long-acting release in patients with metastatic neuroendocrine tumors pretreated with lanreotide

Background:In the present study we investigated the efficacy andtolerability of i.m. octreotide acetate (octreotide LAR) in patients withmetastatic neuroendocrine tumors (NETs) previously treated and failed on i.m.lanreotide. Patients and methods:Fifteen patients (8 females, 7 males, medianage 67 years, range 28–81 years) with metastatic NETs (8 endocrinepancreatic tumors, 7 midgut carcinoids) were enrolled in the study. Allpatients were in progressive disease (objective: 11 patients, symptomatic: 10patients, biochemical: 11 patients) after treatment with slow releaselanreotide, 30 mg every 14 days for a median time of 8 months (range3–19 months). All patients had measurable disease; 12 patients hadelevated serum and/or urine markers and 11 were symptomatic. Octreotidescintigraphy was positive in 13 of 15 patients. Octreotide LAR wasadministered as i.m. injection at the dose of 20 mg every four weeks untildisease progression. Results:An objective partial response (PR) was documented in onepatient (7%), no change (NC) in six (40%), and progressivedisease (PD) in eight patients (53%). The PR was observed in onepatient with non-functioning endocrine pancreatic tumor with progressive liverand lymph node metastases after 16 months of i.m. lanreotide therapy. Themedian duration of disease stabilization was 7.5 months (range 6–12+months). The overall biochemical response rate was 41%, including CRs(33%) and PRs (8%); biochemical responses were observed incarcinoids as well as in endocrine pancreatic tumors; the median duration ofresponse was 5 months for CRs and 7.5 months for PRs. The overall symptomaticresponse rate was 82%. The median duration of response for diarrhoea,abdominal pain, or both was 6.5 months (range 3–12+ months). Improvementin performance status (PS) was obtained in 5 of 11 patients with PS of 1 atstudy entry.Median duration of octreotide LAR treatment was seven months (range3–12+ months). No serious adverse events were reported; mild sideeffects were reported in 26% of patients. Conclusions:Octreotide LAR 20 mg shows significant efficacy interms of objective response rate (PR + SD), biochemical and symptomaticcontrol in patients with metastatic NETs of the GEP system pretreated andprogressing on slow release lanreotide.     

Somatostatin analogs and prednisone in advanced refractory thymic tumors

BACKGROUND: Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium-labeled octreotide ((111)In-DTPA-D-Phe(1)-octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study. METHODS: Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow-up). In 8 cases, octreotide was replaced by the long-acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated. RESULTS: The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow-up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients). CONCLUSIONS: Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long-acting analog lanreotide, which requires fewer injections, improves patients' compliance.     

Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation

We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m(-2)) and etoposide (100 mg m(-2)) on days 1-3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours.     

A retrospective case study of sunitinib treatment in three patients with Von Hippel-Lindau disease

Von Hippel-Landau (VHL) disease is characterized by malignant and benign tumors in multiple organs. Sunitinib, a tyrosine kinase inhibitor, has been clinically available for treating sporadic patients with recurrent or unresectable and metastatic clear renal cell carcinomas (cRCCs) and metastatic lesions of the lung, but its effect on VHL disease-associated tumors remains poorly understood. This retrospective case series examined the effect of sunitinib on RCC, hemangioblastomas, pheochromocytomas, and pancreatic neuroendocrine tumors in patients with confirmed VHL. Of note, three patients with VHL disease who were treated with sunitinib were identified from a review of their medical records. The efficacy of sunitinib was evaluated by comparing computed tomography (CT) or magnetic resonance imaging (MRI) scans conducted before and after treatment. Adverse side effects associated with sunitinib were assessed and recorded. All three patients with VHL disease exhibited clinical improvement after treatment with sunitinib. Patient 1 exhibited a decrease in the size of both their pheochromocytoma and RCC after 19 months of sunitinib treatment. RCCs in Patients 2 and 3 exhibited stable response to sunitinib for approximately 1 and 6 years, respectively. All the patients reported tolerable side effects. Therefore sunitinib treatment was associated with either partial response or stable control of VHL-related RCCs, pheochromocytomas and pancreatic neuroendocrine tumor (NET) with acceptable side effects. Further evaluation of sunitinib in patients with VHL disease in larger prospective studies is warranted.     

Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group.

PURPOSE: Somatostatin analogs and interferon alfa control hormone-active/functional neuroendocrine gastroenteropancreatic tumors. In addition to hormonal control, variable degrees of antiproliferative effects for both agents have been reported. Until now, however, no prospective, randomized studies in therapy-naive patients have compared somatostatin analogs or interferon alfa alone with a combination of the two. METHODS: Eighty therapy-naive patients with histologically verified neuroendocrine tumor disease (primary localization: foregut, n = 36; midgut, n = 30; hindgut, n = 3; unknown, n = 11; functional, n = 29; nonfunctional, n = 51) were randomly treated either with lanreotide (1 mg three times a day administered subcutaneously [SC]) or interferon alfa (5 x 106 U three times a week SC) or both. All patients had disease progression in the 3 months before study entry, verified with imaging procedures. RESULTS: Twenty-five patients were treated with lanreotide, 27 patients were treated with interferon alfa, and 28 patients were treated with the combination. Partial tumor remission was seen in four patients (one patient who received lanreotide, one patient who received interferon alfa, and two patients who received the combination). During the 12 months of therapy, stable disease was observed in 19 patients (seven patients who received lanreotide, seven patients who received interferon alfa, and five patients who received the combination), whereas tumor progression occurred in 14 of 25 patients (lanreotide), 15 of 27 patients (interferon alfa), and 14 of 28 patients (combination). Side effects leading to an interruption of therapy were more frequent in the combination group than in the monotherapy arms. CONCLUSION: This prospective, randomized, multicenter study shows for the first time that somatostatin analogs, interferon alfa, or the combination of the two had comparable antiproliferative effects in the treatment of metastatic neuroendocrine gastroenteropancreatic tumors. Response rates were lower compared with those published in previous, nonrandomized studies. The antiproliferative effect of the tested substances was similar for functional and nonfunctional neuroendocrine tumors.     

Successful use of pazopanib for treatment of refractory metastatic hemangiopericytoma

Hemangiopericytoma is a rare disease entity of soft-tissue sarcoma (STS) that can be cured with surgical resection. In cases of inoperable recurrence or metastasis, palliative chemotherapy is indicated, though there is currently no approved chemotherapy regimen. Therefore new treatment regimens are needed.We describe three cases of metastatic hemangiopericytoma. In the first case, five lines of chemotherapeutic agents were used unsuccessfully in a patient with a 12-year history of metastatic hemangiopericytoma. After one cycle of pazopanib therapy, however, chest radiography showed a decrease in tumor volume of more than 30%. A marked decrease in FDG uptake on PET CT was also noted, and the patient is now on her 5^th month of pazopanib therapy. The second case is a patient with a brain hemangiopericytoma with multiple liver, lung, and bone metastases. Pazopanib induced radiologic stabilization of metastatic disease over the course of 8 months. The third case is a patient with a retroperitoneal hemangiopericytoma with pleural and peri-renal metastases. For more than 8 months, he has exhibited stable disease with pazopanib treatment.Pazopanib may be useful for treatment of metastatic hemangiopericytoma, though further studies are needed to confirm the efficacy of this medication and to investigate its molecular mechanism of action.     

High-voltage irradiation and combination chemotherapy for malignant pheochromocytoma

A 29-year-old man with metastatic extraadrenal pheochromocytoma developed paraplegia which reversed completely after megavoltage irradiation of the dorsolumbar spine. Later, treated with cyclophosphamide, vincristine, and dacarbazine, he had a temporary decrease in plasma norepinephrine concentration, a partial recalcification of bone lesions, and a decrease in the need for antihypertensive treatment for 12 months. Irradiation and combination chemotherapy should be evaluated further in the management of malignant pheochromocytoma.     

Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs

Somatostatin analogs and α-interferon induce good responses as single drugs in the treatment of endocrine pancreatic tumors. We examined the efficacy and tolerability of the combination of α-interferon and somatostatin analogs in 16 patients with metastatic endocrine pancreatic tumors. All patients except one had received prior treatment and were in a progressive state. Doses of α-interferon and somatostatin analogs were individually titrated. The α-interferon doses varied between 9 and 25 million units per week and were combined with 100–1500 μg of octreotide or 6000 μg of lanreotide daily. Radiological response was seen in 3 of 16 (19%) patients (median duration 23 mo). Biochemical response was seen in 10 of 16 (62.5%) patients (median duration 22 mo). All three patients previously progressing on both α-interferon and somatostatin analog as single drugs achieved a stabilization of the disease when treated with the combination (median duration 10 mo). Seven of eight (88%) patients previously progressing on α-interferon treatment benefited from the combination with biochemical partial response or stabilization. All six patients previously progressing during somatostatin analog treatment achieved biochemical partial response or stabilization. More than 80% of patients who progressed during previous treatment with either drug benefited from the combined treatment, which also was well tolerated. Thus, a combination of α-interferon and somatostatin analogs may be considered for patients previously progressing on treatment with α-interferon or somatostatin analogs. However, in this study, the value of sequential treatment has not been evaluated.     

Remission of Merkel cell tumor after somatostatin analog treatment

We recently treated one patient presenting with a disseminated non-operable Merkel cell carcinoma (MCC) by lanreotide (somatostatin analog), with a complete remission of the disease and a follow up of 17 months. We present in this paper a case report with a review of the utilization of somatostatin analogues in the treatment of MCC.     

Phase I-II study of the somatostatin analogue lanreotide in hormone-refractory prostate cancer

Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin growth factor 1 (IGF1). A total of 30 patients with hormone-refractory prostate cancer were treated with a slow-release formulation of lanreotide. The mean age was 71 years. Patients were treated with one intramuscular injection of 30mg BIM 23014 once a week and were followed for prostage-specific antigen (PSA) level evolution until disease progression or WHO grade 3 or 4 toxicity and for survival. The patients were treated for a mean duration of 12 weeks (range, 2–60 weeks). The performance status and bone pain were improved in 40% and 35% of patients, respectively. In all, 20% of the patients had a decrease of 50% in PSA levels and 16% showed a stabilization. The biological response was correlated with clinical improvement. The 1-year global survival rate was 72%, with the rate being 89% in the group of patients who were responders on PSA plasma level and 64% in patients with progressive disease. The response duration ranged from 16 to 60 weeks. Toxicity was minor, with transient grade I digestive side effects being noted in a few patients. Lanreotide given at 30 mg once a week to patients with metastatic hormone-refractory prostate cancer was well tolerated. The response rate was higher than that reported in recent published series. Higher doses of lanreotide should be evaluated.     

Neuroendocrine small cell carcinoma of the uterine cervix: what disease? What treatment? Report of ten cases and a review of the literature

Neuroendocrine small cell carcinoma of the uterine cervix (NESCCC) is an entity with very aggressive behaviour. The optimal initial therapeutic approach to this rare disease has not yet been clearly defined.We reviewed our experience of this disease over the past 10 years with regard to chemosensitivity. Since 1988, ten patients (mean age 33 years; range 24–47) have been diagnosed with NESCCC and treated in our institutions. Disease stage at presentation was IA (one), IB (five, two with lymph node involvement), IIB (one), IIIB (one), and IV (two). One patient had metastatic disease at presentation; three developed metastases during initial treatment. Eight patients underwent surgery and eight received radiation therapy. Six patients received pre- or postoperative cisplatinumvepeside (PE) combination chemotherapy, either alone or concurrently with radiation therapy. PE alone as primary chemotherapy led to disease stabilization in the two patients so treated; concurrent PE and radiation therapy resulted in a pathological complete response in one patient. Eight patients relapsed within 16 months and died of their disease within 29 months from the initial diagnosis. Two patients are alive with no evidence of disease at 13 and 53 months.Our series confirms the previously described very poor prognosis of NESCCC, despite initial aggressive multidisciplinary treatment. It may be that the introduction of chemotherapy, especially combined primary chemoradiotherapy, might allow patients to do a little better, although at the moment there is no good evidence one way or the other.     

嗜铬细胞瘤的手术治疗:11例报告

背景与目的：嗜铬细胞瘤临床上少见,无高血压或无其他症状者容易误诊,手术切除可治愈,但在术前无准备或准备不充分情况下手术风险极大。本文报告我们手术治疗嗜铬细胞瘤的经验。方法：回顾性分析11例嗜铬细胞瘤患者的临床资料,着重总结该病手术前、手术中控制血压的方法和手术经验。结果：11例患者均手术成功切除肿瘤,术后随访3个月—10年,全部病例血压恢复正常,症状消失。1例术后半年在腰交感链部位肿瘤复发,再次手术切除后治愈。结论：嗜铬细胞瘤最根本的治疗是手术切除,充分的术前准备和手术技巧是保证手术成功的关键。     

Antitumor effects of somatostatin analogs in neuroendocrine tumors

Background.

For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs.

Methods.

A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts.

Results.

In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20–0.59; p = .000072).

Conclusions.

In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs.     

Case report of metastatic familial pheochromocytoma treated with cisplatin and 5-fluorouracil

Summary We report on a rare case of malignant pheochromocytoma in a patient with a family history of this disease. After three cycles of treatment with cisplatin and 5-fluorouracil, a decrease in the need for antihypertensive treatment occurred, which lasted almost 2 years despite the discontinuation of chemotherapy. The patient showed an objective response, which was technically a minor response, although in this slow-growing tumor it was of major clinical significance. This chemotherapy regimen may play a role in the management of malignant pheochromocytoma.     

Patient‐Reported Symptom Control of Diarrhea and Flushing in Patients with Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a Randomized,Placebo‐Controlled,Double‐Blind and 32‐Week Open‐Label Study

Background

In the double‐blind (DB) ELECT study, lanreotide depot/autogel significantly reduced versus placebo the need for short‐acting octreotide for symptomatic carcinoid syndrome (CS) control in neuroendocrine tumor (NET) patients. Here we present patient‐reported symptom data during DB and initial open‐label (IOL) treatment.

Materials and Methods

Adults with NETs and CS history, with/without prior somatostatin analog use, were randomized to 16 weeks’ DB lanreotide 120 mg subcutaneous or placebo every 4 weeks, followed by 32 weeks’ IOL lanreotide. Patients recorded diarrhea and/or flushing frequency and severity daily by Interactive Voice (Web) Response System for 1 month prior to randomization and throughout the study.

Results

Of 115 patients randomized (n = 59 lanreotide, n = 56 placebo), 56 lanreotide and 45 placebo patients enrolled in the IOL phase. During DB treatment, least square (LS) mean percentages of days with moderate/severe diarrhea and/or flushing were significantly lower for lanreotide (23.4%) versus placebo (35.8%; LS mean difference [95% confidence interval]: ?12.4 [?20.73 to ?4.07]; p = .004). For DB lanreotide patients, average daily composite (frequency × severity) diarrhea scores improved significantly between DB and IOL treatment (mean difference: ?0.71 [?1.20 to ?0.22]; p = .005), and remained stable for diarrhea and/or flushing. For DB placebo patients, composite scores for diarrhea, flushing, and diarrhea and/or flushing improved significantly between DB and IOL treatment (mean differences: ?1.07 [?1.65 to ?0.49]; ?1.06 [?1.93 to ?0.19]; and ?2.13 [?3.35 to ?0.91]; all p ≤ .018).

Conclusion

Improved diarrhea and flushing control in CS patients during 16‐week lanreotide treatment was sustained during maintenance of lanreotide treatment for the 32‐week IOL phase (48 weeks total).

Implications for Practice

This study prospectively collected daily patient‐reported data on diarrhea and flushing from the ELECT trial to evaluate the direct impact of lanreotide depot on patients’ relief of carcinoid syndrome symptoms. Treatment with lanreotide depot was associated with significant reductions in the percentages of days patients reported symptoms of diarrhea and flushing, as well as reductions in the frequency and severity of daily symptoms compared with placebo during 16 weeks of double‐blind treatment. These improvements were sustained for 32 additional weeks of open‐label lanreotide treatment (i.e., through week 48 of treatment), resulting in clinically meaningful, long‐term symptom reduction.     

Radiation treatment of recurrent pheochromocytoma of the bladder: case report and review of literature

Secondary to the paucity of pheochromocytoma, very limited data exist regarding the optimal treatments of metastatic disease. Malignant pheochromocytomas are often considered unresponsive to radiotherapy, but this decision is based on the few case reports performed before 1970. There have been a handful of reports about metastatic resolution and palliation from radiation therapy. Nevertheless, radiotherapy is not considered a mainstay of pheochromocytoma treatment. In this case report, we describe a patient with a malignant extraadrenal pheochromocytoma, metastatic to the right humerus, and her treatment course of surgery and radiotherapy.     

The Use of Lanreotide Autogel? in the Treatment of Intestinal Obstruction in a Patient with Adenocarcinoma

Intestinal obstruction is a common complication in patients with advanced abdominal or pelvic cancer. The synthetic somatostatin analogue octreotide can help relieve nausea, vomiting and pain in patients with inoperable obstruction. Here, we report a case of recurrent intestinal obstruction in a patient with adenocarcinoma. Although the obstruction was resolved after 3 days of treatment with octreotide, new episodes of obstruction occurred, resulting in a delay of the chemotherapy treatment. After 3 episodes of obstruction, we initiated treatment with a longer-acting somatostatin analogue, lanreotide Autogel® 120 mg, administered once every 4 weeks. The treatment with lanreotide Autogel is being continued, allowing for continuation of the chemotherapy without further episodes of intestinal subocclusion or obstruction. Until November 2013, the patient received eighteen 4-weekly injections of lanreotide Autogel and did not report side effects. This case report demonstrates the successful treatment of intestinal obstruction with lanreotide Autogel in a patient with adenocarcinoma.Key words: Intestinal obstruction, Adenocarcinoma, Somatostatin analogue, Lanreotide Autogel®