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Journal of Analytical Oncology

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.

Keywords: Adenocarcinoma, efficacy, erlotinib, fixed-dose-rate infusion, gemcitabine, pancreas, safety.
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Journal of Analytical Oncology

Biomarkers of Oxidative Stress, Proliferation, Inflammation and Invasivity in Saliva from Oral Cancer Patients 
Pages 52-57
Radu Radulescu, Alexandra Totan, Bogdan Calenic, Cosmin Totan and Maria Greabu

DOI:
http://dx.doi.org/10.6000/1927-7229.2015.04.01.9
Published: 12 February 2015


Abstract: Cancer represents the main cause of death in the economically developed countries and the second cause of death in developing ones. Head and neck squamous cell carcinomas are the sixth most common malignancies worldwide with oral cavity and pharynx cancers being the most common. Saliva qualifies as one of the most suitable diagnostic fluids due to the non-invasivity nature, simple handling procedures, easy collection and storage and good cooperation with patient groups such as children or persons with disabilities.

The aim of the present study is to assess the presence in saliva of several cancer biomarkers such as: tumor cells proliferation - Ki-67 Antigen and Squamous Cell Carcinoma Antigen (SCCA), inflammation - Interleukin-6 (IL-6), extracellular matrix collagen degradation - Matrix Metallo-proteinase-9 (MMP-9) and Tissue Inhibitor of Metalloproteinases 2 (TIMP-2), oxidative stress - total antioxidant capacity and uric acid. Both uric acid and total antioxidant capacity showed decreased levelsin the saliva of oral cancer patients. IL-6, Ki-67, SCCA and MMP-9 showed increased levels in the saliva of oral patients compared to the control group. Salivary TIMP-2 levels were also decreased in the patients group. We can conclude that salivary diagnosis has the potential of becoming a powerful tool in detecting and monitoring oral cancer patients.

Keywords: MMP-9, TIMP-2, IL-6, Ki-67, SCCA, saliva, oral cancer.
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Journal of Analytical Oncology

Angioimmunoblastic T-Cell Lymphoma: Clinical Aspects and Recent Advances in Biology and Therapy
Pages 191-200
Bernardo Garicochea, Alessandro Igor Cavalcanti Leal, Fernando Sérgio Blumm Ferreira, Volney Assis Lara Vilela, Alesso Cervantes Sartorelli, Yana Novis, Paulo Marcelo Gehm Hoff
DOI:
http://dx.doi.org/10.6000/1927-7229.2014.03.04.2
Published: 29 October 2014


Abstract:  Angioimmunoblastic T-cell lymphoma (AITL) comprehends 20% of the peripheral T-cell lymphomas (PTCL). Although rare, its clinical features may overlap with many other inflammatory, infectious or neoplastic disorders. Therefore, that patients are often diagnosed with advanced stage disease, which contributes for the disease´s dismal prognosis. The clinical presentation of AITL is frequently an assemblage of symptoms including generalized and painful lymphadenopathy, multiple cutaneous alterations, hypergammaglobulinemia, fever, loss of weight and significant autoimmune phenomena. Recent advances in AITL biology have implicated a cell with T-follicular helper phenotype as the origin of the disorder. This rare type of T lymphocyte has a peculiar capacity of interact with microenviroment, which results in an important production of cytokines, explaining the clinical findings of this type of lymphoma. In addition to its pathologic features, AITL can be distinguished from other T-cell lymphomas based on gene expression arrangement, suggesting that AITL has a uniquebiology. Moreover, somatic mutations in the epigenetic regulators DNMT3A, TET2, IDH2, and, especially, in the multifunctional RHOA GTPase gene, have emerged as very consistent genetic abnormalities in AITL. Considering its low incidence, the development of clinical trials in AITL is a challenging matter. Furthermore, the majority of data available originates from studies that contain other subtypes of PTCL, making prognosis analysis and treatment decision a tough work. In this review, we discuss the biological and clinical aspects of AITL and the alternatives for frontline treatment and the management of relapsed disease.

Keywords: Angioimmunoblastic T-cell lymphoma, T-follicular helper cells, gene expression profiling, TET2 mutation, RHOA GTPase mutation, relapsed disease.
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Journal of Analytical Oncology

Metastatic Bone Marrow Tumors Manifested by Hematologic Disorders: Study of Thirty-Four Cases and Review of Literature
Pages 185-190
Guan Min Lai, Jen-Tsun Lin and Cheng-Shyong Chang
DOI:
http://dx.doi.org/10.6000/1927-7229.2014.03.04.1
Published: 29 October 2014


Abstract:  Purpose: Bone marrow metastasis of cancer is a sign of extensively hematogenous spreading of cancer and may be a terminal event of those patients. With the improvement of systemic chemotherapy for malignant disease, some patients may have longer survival. We plan to find out the clinical hematologic presentation and prognostic factors in cancer patients with bone marrow metastasis.

Materials & Methods: In this retrospective study, we reviewed the results of 162 bone marrow examination carried out in adult malignancy patients (colon, lung, gastric, breast and prostate cancers) between January 2002 and December 2012 in Changhua Christian Hospital. The indication for bone marrow study for those patients with hematologic disorders included: leukoerythroblastosis, microangiopathic hemolytic anemia, unknown etiology of anemia, thrombocytopenia, bicytopenia and pancytopenia. Statistics analysis used SPSS 18.0 and overall survival was analyzed with the use of Kaplan–Meier curves and the log-rank test.

Results: Thirty-four patients (20.9%) had evidence of involvement of the bone marrow by a solid tumor, most common cancers were prostate and lung. At the time of diagnosis, the most common hematologic disorders were leukoerythroblastosis and microangiopathic hemolytic anemia. Median survival after the diagnosis of bone marrow metastasis with supportive care only compared with definite treatments was 0.3 months and 20.6 months (p<0.0001). Patients with visceral organ metastasis (0.4 months vs 6.4 months, respectively; p <0.002) and anemia (2.1 months vs 6.4 months, p=0.031) had inferior survival. Patents without any cytopenia had better survival (12.5 months vs 4.1 months, p=0.029). Initial level of thrombocyte and neutrophil, bone marrow infiltration type (focal or diffuse) and disease status were not significant prognostic factor.

Conclusions: Visceral metastasis and anemia are most poor prognostic factors in solid cancers with bone marrow metastasis. Since the improvement of the diagnosis and treatment for cancers during the recent decades, a portion of patients can be had better disease control after definite treatment especially in breast and prostate cancers with bone marrow metastasis.

Keywords: Bone marrow metastasis, leukoerythroblastosis, microangiopathic hemolytic anemia, bone marrow involvement, adenocarcinoma.
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Journal of Analytical Oncology

Diffuse Alopecia Areata Associated with a Solid-Organ Malignancy: Case Report and Literature Review
Pages 201-204
A. Trink, Y. Ramot and F. Rinaldi
DOI:
http://dx.doi.org/10.6000/1927-7229.2014.03.04.3
Published: 29 October 2014


Abstract:  Alopecia areata (AA) is an autoimmune disease, manifesting as non-scarring hair loss. Here we report a 57-year-old woman, who presented with sudden diffuse non-scarring hair loss on the scalp. Histology confirmed the diagnosis of AA. Imaging studies revealed the presence of an irregular mass in the left kidney, and histology demonstrated spindle cell-type renal cell carcinoma. There was spontaneous regrowth of hair after surgical and chemotherapy treatments. Reports of AA as first manifestation of malignancy are uncommon, and to our knowledge, this is the first report of AA as a paraneoplastic manifestation of renal cell carcinoma. This report also suggests that screening for malignancy should be considered in older patients, who present with sudden and diffuse AA.

Keywords: Alopecia areata, kidney cancer, autoimmune disease, paraneoplastic alopecia, hair loss disease.
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