Vol 2 No 2 (2020)

• Role of Cetuximab Re-introduction and Re-challenge in Later Lines of Treatment in Metastatic Colorectal Cancer: A Case Series

  Amrou Shaaban, Asit Mohanty, Yousef Abo Eseud, Jasem Albarrak

  Colorectal cancer (CRC) is the third-largest cancer in the world and has the second-highest mortality rate, characterized by poor prognosis and high metastasis. The early symptoms of CRC are mostly inconspicuous and it is usually diagnosed in the advanced stages. Nearly half of the patients diagnosed with metastatic colorectal cancer (mCRC) are inoperable and have high chances of recurrence and metastasis. Combination therapy with cetuximab and chemotherapy is considered the first-line treatment for mCRC. In patients with Kirsten RAt Sarcoma wild-type mCRC, re-challenge and maintenance therapy with cetuximab was found to be beneficial. However, the disease progression is inevitable. This paper discusses three different cases of metastatic adenocarcinoma in the colon and rectum treated with the re-introduction and re-challenge of cetuximab in combination with chemotherapy. The treatment was found to be effective in treating mCRC in later lines of therapy where treatment options are scarce.

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• To Use or not to Use Anticoagulation in Patients with Advanced Malignancies? – This is the Question Should we use a more flexible approach to cancer-associated thrombosis?

  Katarzyna Rygiel

  The management of cancer-associated thrombosis (CAT) often presents challenges to members of medical teams, attending to patients with advanced malignancies. In general, indications for treatment of CAT have been driven by the randomized clinical trials (RCTs) that have usually excluded patient populations suffering from metastatic cancers, at the end-of-life period. Since the findings of such RCTs are not representative of this particular group of oncology patients, medical providers need practical help in the daily care of this population. It should be noted that venous thromboembolism (VTE) associated with cancer has been related to increased morbidity and mortality rates, as well as different symptoms that can deteriorate the patient’s quality of life (QoL). Therefore, current guidelines promote the use of anticoagulation therapy in oncology patients, focusing on the acute care contexts (e.g., a perioperative period, or chemotherapy (CHT) regimen). In contrast, in the palliative care (PC) setting, the main benefit of anticoagulation should be a reduction of symptom burden associated with VTE. However, during end-of-life care, the risk of bleeding can often overweight the potential benefits of anticoagulation. To shed some light on these complicated issues, this mini-review presents some challenges in CAT anticoagulation management. It briefly discusses VTE risk factors and therapeutic options and compares acute and PC services. This overview supports therapeutic teams in charge of oncology patients receiving PC services, where the main goal is not life extension but an assurance of the best possible QoL.

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• The Paradigm of T Cells in Shaping Tumor Microenvironment

  Dia Roy, Sayantan Bose, Saikat Dutta, Gaurisankar Sa

  The infiltration of immune cells in the tumor micro-environment is well-documented in cancer patients and the resultant complex interactions are determinants of disease prognosis. Consequently, a proper understanding of this interplay is essential for the development and advancement of therapeutic strategies as well as novel prognostic markers. The co-existence of immune cells with the tumor is often accompanied by an impaired immune response that creates a tumor-promoting micro-environment. T-cell mediated immunity forms the major branch of the immune system that is required to mount an effective response against nascent tumors. Major research in the last few decades indicates that a potent source of immunosuppressive cellular and molecular networks prevailing at the site of tumor is mediated by dysfunctional and defective responses mediated by T cell thereby redirecting and reshaping the destiny of T cell and promoting tumor progression. In this review, we aim to summarize the breakthrough advances in recent years that help us gain a better understanding of the immunosuppressive networks resulting from T-cell anergy, exhaustion, senescence and presence of Treg cells in the tumor micro-environment. We also focus on recent discoveries regarding advance in the Th17 balance, polyfunctionality of T cells as well as T cell stemness that improve our perception of the tumor-immunity interactions. We try to emphasize how such information has an impact on therapeutic development and the clinical outcome of the patients.

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• A Preliminary Phase-2 Study with very High-Dose of Melatonin (1000 mg/day) in Untreatable Advanced Cancer Patients Already Progression on Previous Palliative Therapy with High-Dose Melatonin

  Paolo Lissoni, Giorgio Porro, Carla Galli, Rosalia Codogni, Nicoletta Merli, Giuseppe Di Fede

  It is known since more than 50 years that the pineal gland plays a fundamental role in the natural biological resistance against cancer onset and growth. The anticancer role of the pineal gland is due to the production of several antitumor molecules, the most known of them is the indole hormone melatonin (MLT). Unfortunately, although there are a lot of experimental evidences that MLT is completely non-toxic, no oncologist seem to be interested to the clinical use of MLT in the treatment of human neoplasms, at least from a palliative point of view. However, a few number of clinical studies of MLT in the complementary treatment of cancer has demonstrated that the anticancer activity of MLT is a dose-dependent phenomenon. On this basis, a preliminary study with a very high dose of MLT, consisting of 1000 mg/once day in the evening, was carried out in untreatable cancer patients, who failed to respond to the conventional anticancer therapies, and for whom the only available treatment was the palliative therapy. The treatment was well tolerated, and a disease control was achieved in 54% patients. These preliminary results would justify further clinical studies to generate a new interpretation of cancer control, consisting of the pharmacological reproduction of the same mechanisms responsible for the natural resistance against cancer development.

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