Efficacy and Safety of Fixed-Dose-Rate Infusions of Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer 
Pages 44-51
Alberto Muñoz, Eider Azkona, Estíbaliz Iza, Eluska Iruarrizaga, Abigail Ruiz de Lobera, Itziar Rubio, Joan Manel Mañé, Sergio Carrera, Inés Marrodán Ciordia and Guillermo López-Vivanco
DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.01.8
Published: 12 February 2015

Abstract: Purpose: To evaluate the efficacy and safety of fixed-dose-rate infusions of gemcitabine in combination with erlotinib for advanced pancreatic cancer.

Methods/Patients: Patients with locally advanced (LAPC) or metastatic pancreatic cancer (MPC) without previous treatment for the advanced disease and Eastern Cooperative Oncology Group performance status ≤2 received 1500 mg/m² of gemcitabine in 150-minute infusions (10 mg/m²/minute) on days 1, 8 and 15 in 4-week cycles combined with 100 mg/day of oral erlotinib. The primary endpoint was overall survival (OS).

Results: Sixty-two evaluable patients were enrolled (LAPC, n=16; MPC, n=46). Median OS was 10.0 (95% CI, 7.1-13.0) months. OS was longer in patients with LAPC (p=0.019), females (p=0.010) and patients not receiving opioids (p=0.027). A trend towards longer OS was shown in patients with grade ≥2 rash (p=0.078). In multivariate analysis, only gender remained statistically significant (p=0.01). Median PFS was 4.9 (95% CI, 3.1-6.8) months, which was longer in patients with LAPC (p=0.004) and females (p=0.013). Overall response rate was 12.9% (95% CI, 4.7-21.3), with eight patients achieving partial response, and tumour growth control rate was 67.7% (95% CI, 79.3-56.1). The main grade 3/4 adverse events were neutropenia (40.3%), asthenia (22.6%), anaemia (19.4%), thrombocytopenia (17.7%) and infections (14.5%). Three patients died due to septic shock, cholangitis or pulmonary embolism.

Conclusions: The combination of fixed-dose-rate infusions of gemcitabine and erlotinib represents a feasible and active regimen for advanced pancreatic cancer with a manageable safety profile.

Emerging Role of ¹⁷⁷Lu in Nuclear Oncology: A Brief Review
Pages 148-153

Khan Anna and Chadha D. Vijayta
https://doi.org/10.6000/1927-7229.2017.06.04.2

Published: 14 December 2017

Abstract: With the innovations in nuclear medicine techniques, Lutetium 177 (¹⁷⁷Lu) has epitomized as a revolutionary theranostic agent- with both scintigraphic and therapeutic properties. The present review focusses on the introduction of ¹⁷⁷Lu as a promising modality for tumor diagnosis and therapy in widespread metastases . Being a shorter β-range emitter providing better irradiation of smaller tumor volumes, ¹⁷⁷Lu- based PRRT is being increasingly used in patients with somatostatin receptor positive neuroendocrine tumors. Clinical trials with ¹⁷⁷Lu–DOTATATE and ¹⁷⁷Lu–DOTATOC have gained considerable interest in recent years with successful tumor regression in patients with malignant metastatic neuroendocrine tumors. Especially, therapy with ¹⁷⁷Lu-DOTATATE PRRT has reported to significantly improve the quality of life of Gastroenteropancreatic NET patients because of higher affinity of DOTATATE for the somatostatin type 2 receptors. In addition, this review also sheds light on the diagnostic and palliative aspects of ¹⁷⁷Lu which also serves to be an attractive candidate for the preparation of radiopharmaceuticals for radiation synovectomy of small to medium sized joints. Enlisting all the said features, ¹⁷⁷Lu is strongly emerging as a promising theranostic agent that could possibly endow Nuclear Medicine an edge over other conventional therapies in near future.

Keywords: Theranostic agent, somatostatin receptor, radionuclide therapy, radioimmunotherapy, imaging agent.

Efficacy of Chemiluminescence (ViziLite™) as a Screening Method in the Detection ofClinically Suspicious Oral Cancerous and Precancerous Lesions
Pages 176-181
Antonio Carrera Torres, Ángel Martínez-Sahuquillo Márquez, Javier Fernández Farhall, María José Cobos Fuentes and Isabel Gallardo Castillo
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.03.8
Published: 31 July 2013

Abstract: Several screening techniques based on light interaction with tissue have been described to aid clinicians in the detection of early oral cancerous lesions. One of the most studied techniques is chemiluminescence. This method has been used in different studies but always by Oral Medicine specialists.

Objective: To evaluate the chemiluminescence system as a screening method in the detection of clinically suspicious cancerous and precancerous oral lesions when used by clinicians without an Oral Medicine Speciality.

Study Design: A total of 100 patients attending the Oral Medicine Unit at the Dental School of the University of Seville were enrolled. All patients were current smokers and were above the age of 40. The clinical examination was performed by dental students who were instructed in the location and recognition of potentially malignant oral disorders, using visual examination and the chemiluminescence test ViziLite Plus ™ (Zila Pharmaceuticals, Phoenix, AZ, USA). To assess the validity of the chemiluminescence test as a screening method, a visual exam was performed by a specialist in Oral Medicine which was used as a gold-standard.

Results: Conventional oral visual examination by the Oral Medicine Specialist found 13 lesions suspicious for malignancy, out of which 7 were also detected using the chemiluminescence test. Furthermore, 87 patients were diagnosed as lesion-free, of which 49 obtained negative results during the chemiluminescence test and 38 patients had some sort of lesion. With these results, the test yielded a sensitivity of 0.56 and a specificity of 0.56. These results indicate values similar to other studies, in fact lower sensitivity values, possibly due to the lack of experience of the clinician.

Conclusions: The chemiluminescence test (ViziLite Plus™) did not present any advantages in terms of cost-benefit compared to conventional examination as a screening method for cancerous and precancerous oral lesions.

Emerging Therapeutics for Radioiodide-Refractory Thyroid Cancer
Pages 75-86
Juan Pablo Nicola and Ana María Masini-Repiso

DOI: http://dx.doi.org//10.6000/1927-7229.2016.05.02.5
Published: 06 May 2016

Abstract: Although uncommon, thyroid cancer constitutes the main endocrine neoplasia with an incidence rate that has been increasing steadily over the past decades. Recently, remarkable advances have occurred in understanding the biology of thyroid cancer. Novel germline and somatic point mutations as well as somatic chromosomal rearrangements associated with thyroid carcinogenesis have been discovered. Strikingly, acquired knowledge in the genetics of thyroid cancer has been translated into clinical practice, offering better diagnostic and prognostic accuracy and enabling the development of novel compounds for the treatment of advanced thyroid carcinomas.

Even after 70 years, radioiodide therapy remains as the central treatment for advanced or metastatic differentiated thyroid cancer. However, the mechanisms leading to reduced radioiodide accumulation in the tumor cell remain partially understood. Radioiodide-refractory thyroid cancer metastasis constitutes a central problem in the management of thyroid cancer patients. In recent years, the antiangiogenic tyrosine kinase inhibitors sorafenib and lenvatinib have been approved for the treatment of advanced radioiodide-refractory thyroid carcinoma. Moreover, still on clinical phase of study, oncogene-specific and oncogene-activated signaling inhibitors have shown promising effects in recovering radioiodide accumulation in radioiodide-refractory thyroid cancer metastasis. Further clinical trials of these therapeutic agents may soon change the management of thyroid cancer.

This review summarizes the latest advances in the understanding of the molecular basis of thyroid cancer, the mechanisms leading to reduced radioiodide accumulation in thyroid tumors and the results of clinical trials assessing emerging therapeutics for radioiodide-refractory thyroid carcinomas in the era of targeted therapies.