lutetium-lu-177-dotatate and Digestive-System-Neoplasms

Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system.. To estimate the clinical effectiveness of three interventions [everolimus (Afinitor. The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science.. We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel. Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin. A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials.. Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales.. Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial.. This study is registered as PROSPERO CRD42016041303.. The National Institute for Health Research Health Technology Assessment programme.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Digestive System Neoplasms; Disease Progression; Everolimus; Humans; Lung Neoplasms; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Quality-Adjusted Life Years; Radioisotopes; Randomized Controlled Trials as Topic; Sunitinib

The primary analysis of the phase 3 NETTER-1 trial showed significant improvement in progression-free survival with. This open-label, randomised, phase 3 trial enrolled patients from 41 sites in eight countries across Europe and the USA. Patients were 18 years and older with locally advanced or metastatic, well differentiated, somatostatin receptor-positive midgut neuroendocrine tumours (Karnofsky performance status score ≥60) and disease progression on fixed-dose long-acting octreotide. Patients were randomly assigned (1:1) via an interactive web-based response system to intravenous. From Sept 6, 2012, to Jan 14, 2016, 231 patients were enrolled and randomly assigned for treatment. The prespecified final analysis occurred 5 years after the last patient was randomly assigned (when 142 deaths had occurred); median follow-up was 76·3 months (range 0·4-95·0) in the. Advanced Accelerator Applications, a Novartis company.

Topics: Aged; Antineoplastic Agents, Hormonal; Chemoradiotherapy; Digestive System Neoplasms; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Prognosis; Radiopharmaceuticals; Survival Rate

Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium (177)(Lu) DOTATATE in patients with progressive NETs.. Thirty-seven patients with grade 1 and grade 2 disseminated and progressive gastroenteropancreatic NET were enrolled in a nonrandomized, phase 2 clinical trial. Repeated cycles of 200 mCi (7.4 GBq; ±10%) were administered up to the cumulative dose of 800 mCi (29.6 GBq; ±10%).. Among 32 evaluable patients, partial response and minimal response to treatment were seen in 28% and 3%, respectively, and stable disease was seen in 41% of patients. A total of 28% had progressive disease. A response to treatment was significantly associated with lower burden of disease in the liver. No significant acute or delayed hematologic or kidney toxicity was observed. An impressive improvement of performance status and quality of life were seen after Lu-DOTATATE therapy.. Treatment with multiple cycles of (177)Lu-DOTATATE peptide receptor radionuclide therapy is well tolerated. This treatment results in control of the disease in most patients, whereas systemic toxicities are limited and reversible. Quality of life is also improved.

Topics: Adult; Aged; Digestive System Neoplasms; Disease Progression; Dose Fractionation, Radiation; Female; Fluorodeoxyglucose F18; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multimodal Imaging; Neoplasm Grading; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Predictive Value of Tests; Quality of Life; Radiopharmaceuticals; Receptors, Somatostatin; Texas; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

The purpose of this study is to extend an established SPECT/CT quantitation protocol to (177)Lu and validate it in vivo using urine samples, thus providing a basis for 3D dosimetry of (177)Lu radiotherapy and improvement over current planar methods which improperly account for anatomical variations, attenuation, and overlapping organs.. In our quantitation protocol, counts in images reconstructed using an ordered subset-expectation maximization algorithm are converted to kilobecquerels per milliliter using a calibration factor derived from a phantom experiment. While varying reconstruction parameters, we tracked the ratio of image to true activity concentration (recovery coefficient, RC) in hot spheres and a noise measure in a homogeneous region. The optimal parameter set was selected as the point where recovery in the largest three spheres (16, 8, and 4 ml) stagnated, while the noise continued to increase. Urine samples were collected following 12 SPECT/CT acquisitions of patients undergoing [(177)Lu]DOTATATE therapy, and activity concentrations were measured in a well counter. Data was reconstructed using parameters chosen in the phantom experiment, and estimated activity concentration from the images was compared to the urine values to derive RCs.. In phantom data, our chosen parameter set yielded RCs in 16, 8, and 4 ml spheres of 80.0, 74.1, and 64.5 %, respectively. For patients, the mean bladder RC was 96.1 ± 13.2% (range, 80.6-122.4 %), with a 95 % confidence interval between 88.6 and 103.6 %. The mean error of SPECT/CT concentrations was 10.1 ± 8.3% (range, -19.4-22.4 %).. Our results show that quantitative (177)Lu SPECT/CT in vivo is feasible but could benefit from improved reconstruction methods. Quantifying bladder activity is analogous to determining the amount of activity in the kidneys, an important task in dosimetry, and our results provide a useful benchmark for future efforts.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Digestive System Neoplasms; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Phantoms, Imaging; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Urinary Bladder