Clinical Oncology

[Role of calcium metabolism in malignant diseases]

MÉSZÁROS Szilvia1, TAKÁCS István1

AUGUST 30, 2019

Clinical Oncology - 2019;6(03)

[Calcium plays a key role in a wide range of biologic functions. It is involved in skeletal mineralization, muscle functions, nerve transmission, and hormonal secretion and modulate various cellular functions too. Lines of research, on possible association of calcium metabolism regulation with tumorigenesis have been extensively studied in the recent decades. Implying disruptions and/or alterations of known regulatory and molecular pathways can lead to severe, sometimes life-threatening complications. The shift in physiological regulation and pathological factors also affect bone metastases and hypercalcaemia in cancer patients. For this reason, it is important to know about the changes in calcium metabolism and its treatment options in cancerous diseases.]


  1. Semmelweis Egyetem, I. Sz. Belgyógyászati Klinika, Budapest



Further articles in this publication

Clinical Oncology

[The American Society of Clinical Oncology 2019. Annual The most important news of the congress]


Clinical Oncology


KIS Erika Gabriella

[Tumors with standard electrochemotherapy (ECT) has raised over the past decade from skin cancers to locally advanced or metastatic tumors. The procedure became a reliable alternative of other local tumor ablation methods, because of its patient tolerability, effi cacy across histotypes, and repeatability. ECT is based on the physical phenomenon of reversible electroporation; short electric pulses are applied to tumor nodules to achieve transient cell membrane permeabilization to otherwire poorly permeant chemotherapy drugs, which consequently increases cytotoxicity. At present recognized indications include superfi cial metastases of malignant melanoma, breast cancer, head and neck skin tumors, Kaposi sarcoma, primary and recurrent nonmelanoma skin cancers, and in well-selected patients mucosal oropharyngeal cancers. Emerging applications include skin metastases from visceral or hematological malignancies, vulvar cancer, certain benign skin lesions, and the combination of ECT with systemic immunotherapy. Thanks to the technical developments, the new ECT indications are deep-seated tumors, including bone metastases, liver malignancies, pancreatic and prostate cancers with the use of long needle variable geometry electrodes. Herein we review the present status of ECT from the basic principles to emerging applications, and report the effi cacy of standard ECT across histotypes.]

Clinical Oncology

[Beyond second line therapy in patients with metastatic colorectal cancer: a systematic review]

D. Arnold, G. W. Prager, A. Quintela, A. Stein, S. Moreno Vera, J. Taieb

[Background: The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the effi cacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes. Results: The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefi t for trifl uridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in effi cacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy. Conclusions: These fi ndings support the introduction of an approved agent such as trifl uridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second line treatment.]

Clinical Oncology

[Prevention of drug-related neuropathy in the clinical practice]


[There was a revolution of oncological treatments in the last fi ve years caused by introduction of immuncheckpoint inhibitors. Platinum and taxane based chemotherapies are the standard of care of the most frequent malignancies such as colon and breast cancer. Signifi cant improvement was achieved concerning side effects of chemotherapy in the few past decades. Preventive treatment of vomiting, neutropenia, aneamia are now based on clinical evidences. Meanwhile, there remained side effects (including chemotherapy induced neuropathy) which are diffi cult to treat. This article provides overwiev of the pharmacological therapies, vitamins and non-pharmacological procedures aimed to prevent chemotherapy induced neuropathy. Unfortunately still there are no drugs that are highly effective of preventing of chemotherapy induced periferial neuropathy validated in randomized clinical trials.]

Clinical Oncology

[A chemist’s thoughts about alternative medicine]


[Alternative medicine offers a virtual challenge for classical 21st century evidence based medicine even that the latest is justifi ed by effi cacy and survival improvements. The theoretical basis of the alternative medicine is not justifi ed by experimental or clinical evidence. Ethics of the contemporary pharmacologic marketing equally considers the interest of the patient, the doctor and the pharmacological company. Unfortunately, alternative medicine does not consider market ethics and gains unjustifi ed competitive advantage. Beside the statements of the professional organizations, it is necessary continuously inform the patients and the doctors on the lack of real evidence on the effi cacies of these ”alternative” medical solutions.]

All articles in the issue

Related contents

Hypertension and nephrology

[Novelties in the diagnosis and treatment of X-linked hypophosphatemia]

RUESZ György Sándor, MIKES Bálint, CSIZEK Zsófia, HORVÁTH Orsolya

[X-linked hypophosphataemia (XLH) is the most common inherited cause of phosphate wasting. Its pathogenesis is complex, determined by the dysregulation of phosphate homeostasis and bone metabolism. We review herein the pathophysiology of XLH leading to multiple manifestations, stages of diagnosis and the treatment strategies. XLH is now in the scientific interest of pediatric nephrology, because a new treatment modality, burosumab became available in Hungary. Burosumab is a monoclonal antibody against fibroblast growth factor 23 (FGF-23). XLH is caused by the loss of function mutations in ”phosphate regulating endopeptidase homolog, X-linked” (PHEX) gene, which results enhanced secretion of the phosphaturic hormone FGF-23. The diagnosis of XLH is based on signs of rickets and/or osteomalacia and decreased growth velocity in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Conventional treatment with oral phosphate supplementation together with active vitamin D (calcitriol or alfadiol) can improve bone metabolism, but only partial results can be achieved, and can promote side effects (nephrocalcinosis). The better understanding of the role of PHEX gene and FGF-23 levels in the pathomechanism helped to identify therapeutic options more properly. With monoclonal antibody therapy against FGF-23 the disease process can be interrupted, and complications can be prevented if the therapy is initiated in time. However, deformities already leading to disability cannot regress completely during burosumab therapy, highlighting the need of early diagnosis and the start of the biological treatment before complications.]

Clinical Neuroscience

[Calcium ion is a common denominator in the pathophysiological processes of amyotrophic lateral sclerosis]

PATAI Roland, NÓGRÁDI Bernát, MESZLÉNYI Valéria, OBÁL Izabella, ENGELHARDT József István, SIKLÓS László

[Amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease is characterized by progressive muscle weakness caused by the degeneration of the motor neurons in the spinal cord and motor cortex. However, according to the recent observations, ALS is a rather complex syndrome which frequently involves symptoms of cognitive impairment. Therefore, ALS cases can be interpreted in a clinico-pathological spectrum spanning from the classical ALS involving only the motor system to the fronto-temporal dementia. The progression of the disease, however, manifested in the degeneration of the upper and lower motor neurons, is based on the same complex pathobiology. The main elements of the pathomechanism, such as oxidative stress, excitotoxicity, immune/inflammatory processes and mitochondrial dysfunction are well described already, which operate in orchestrated way and amplify the deleterious effect of each other. It is assumed that calcium ions act as a catalyst in this interaction, hence each of the individual mechanisms has strong, positive and reciprocal calcium dependence thus may combine the individual pathological processes into a unified escalating mechanism of neuronal destruction. This review provides an overview of the role of calcium in connecting and amplifying the major mechanisms which lead to degeneration of the motor neurons in ALS. ]


[The role of alfacalcidol in the prevention of osteopenia following renal transplantation]


[AIM - The aim of this prospective study was the long-term evaluation of the effect of calcium and alfacalcidol treatment on calcium metabolism in patients with renal transplantation. METHODS - Patients were divided in two groups. Patients in Group 1 (n=159) received calcium substitution, while patients in Group 2 (n=81) were treated with alfacalcidol. Serum Ca, P, Mg, alkaline phosphatase (AP) and PTH levels were determined before and after transplantation regularly for three years. Femur neck and lumbar vertebral bone mineral densities (BMD) were measured at the same time after transplantation. RESULTS - After transplantation the mean serum calcium level significantly increased, while the mean serum phosphate level significantly decreased in both groups. After the operation the PTH levels decreased in both groups and it was found to be more pronounced in the alfacalcidol group.The majority of patients had osteopenia in the follow-up period. Between the third month and the third year after transplantation, BMD increased by 9.4% in Group1, and decreased by 4% in Group 2 at the lumbar spine. At 3 years the mean BMD value at the femoral neck was increased by 6.5% in Group 1, and by 6.7% in Group 2, compared to the 3-month values.The change in BMD was only significant at the lumbar spine, in Group 1 (p=0.019). During the follow-up period osteonecrosis was diagnosed in 6 patients in Group 1 and in 9 cases in Group 2. CONCLUSION - Alfacalcidol treatment decreased secondary hyperparathyroidism more rapidly and effectively, which was also indicated by the more pronounced decrease of serum PTH levels. During the 3 years follow-up period, BMD increased in both groups except for the lumbar spine in Group 2, however, the majority of the patients still had osteopenia.The study could not demonstrate a superiority of alfacalcidol over calcium supplementation in the prevention of posttransplantational osteopenia.]

LAM Extra for General Practicioners



[Various medical associations issue different recommendations for the prevention and treatment of vitamin D deficiency. These significant differences are partly explained by the different definition of normal vitamin D level and the use of completely different mathematical models to predict the increase in vitamin D level as a response to therapy. According to the Institute of Medicine (IOM), the target vitamin D level is 20 ng/ml, whereas the Endocrine Society (ES) recommends 30 ng/m as the miminum target value. According to the ES, a 1 ng/ml increase of vitamin D level can be reached by a daily intake of 100 NE, while the IOM recommends 3.6 ng/ml. Moreover, the IOM states that the effect of therapy on serum level is nonlinear. These differences show that the ES and IOM have different views on the risk of adverse effects. The IOM recommends 400 IU vitamin D daily for children younger than 1 year, 800 IU for those above 70 years and 600 IU/per day for everyone else. The ES recommend 400-1000 IU daily for all infants and 1500- 2000 IU for adults. Screening, however, is not recommended by either society. To decrease uncertainty concerning the side effects of higher-dose vitamin D treatment, it is important to understand, use and support the function of the pharmacovigilance system of the pharmaceutical industry that manufactures and markets various (prescription, over-the-counter) preparations. This is what the author aims to highlight in the second part of this article. Using this system, both the doctor and the patient can help support and accept the justification of higher-dose vitamin D therapy.]

Clinical Oncology

[Bone metastases - Current treatment strategy]

BOÉR Katalin, NÉMETH Zsuzsanna

[Bone is the most common site of metastatic disease in many solid tumours, mainly in breast, prostate and lung cancer. Patients with bone metastases are at risk for skeletal-related events such as bone pain, pathological fractures requiring surgery and/or radiation to bone lesions, hypercalcemia, and spinal cord compression. Skeletal-related events are major source of morbidity for cancer patients and may be associated with negative impact on quality of life and survival. Bisphosphonates inhibit osteoclast function and are widely used in the treatment of malignant bone disease, as preventive therapy against skeletal-related events. Recently, the NF-κappa B-ligand (RANKL)-mediated osteoclast activity and this pathway in bone metabolism became a prime target for the treatment of bone metastases. The fi rst drug targeting the RANK-RANKL pathway is denosumab, a fully monoclonal human antibody which binds to RANKL and inhibits osteoclast activity. Nowadays optimal treatment of bone metastases requires multidisciplinary management of patients including the administration of bone-modifying agents such bisphosphonates or denosumab. The use of bone-targeted agents is a valuable additional treatment in the fi ght against bone metastases and multiple, randomised trials have demonstrated the effectivity of these drugs in reducing skeletal morbidity caused by advanced cancer.]