Autoimmunity can be associated with cancer and one of the forms of its expression is the developm... more Autoimmunity can be associated with cancer and one of the forms of its expression is the development of antibodies to autologous cellular antigens. The types of cellular proteins which induce autoantibody responses in gastrointestinal malignancies are quite varied and include cellular proteins encoded by mutated normal genes (p53), cellular proteins that are overexpressed and/or aberrantly expressed in malignant tissues (carcinoembryonic antigen), inhibitors of apoptosis (survivin and livin), major components of mucus (mucins), surface receptors of apoptosis (Fas) and nuclear-restricted proteins (double-stranded DNA, single-stranded DNA and Sm family proteins). In the past few years, due to the great clinical interest and the advancement in detection techniques, the above list has grown significantly and a large number of cancer-related antigens, which trigger a specific humoral immune response to the host, have also been identified. The authors review the autoantibodies associated with gastrointestinal malignancies and their clinical implications.
The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and ... more The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.
Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, app... more Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, approved as first line treatment concurrently administrated with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer. One of the most common side effects, rash, is possibly linked to overall and progression-free survival and may serve as a potential surrogate marker. Nevertheless, erlotinib-induced rash is cause of negative impact on patients' quality of life and often can trigger discontinuation of treatment. Adequate and timely management of rash depending on the grade of rash is important for therapy continuation.
Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is c... more Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.
Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing... more Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing ones. Multiple molecules regulate angiogenesis, such as the vascular endothelial growth factor, angiopoietins, the fibroblast growth factor, the platelet-derived growth factor and the transforming growth factor-β. Angiogenesis plays an important role in the growth, progression and metastasis of a tumour. Inhibiting the angiogenic process or targeting existing tumour vessels can be used for treatment of tumours as an alternative or in parallel with conventional chemotherapy. Many anti-angiogenic factors are under investigation and some are already being used in clinical practice with various results.
The diagnosis of pancreatic cancer is devastating for patients and their relatives as the inciden... more The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.
Prostate cancer is one of the leading causes of cancer related death in men, and remains incurabl... more Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC). In an attempt to improve survival benefit, several novel drugs targeting specific pathways involved in cell signaling, proliferation, angiogenesis, apoptosis and immune modulation are currently under investigation either as single agents or in combination with cytotoxic drugs. Clinical trials evaluate the inhibition of prostate cancer cells growth by targeting the nuclear receptor of vitamin D alongside cytotoxic therapy. Angiogenesis inhibitors as well as epidermal growth factor receptor blockage are also under clinical investigation in several combinations. Immunomodulatory agents and autologous dendritic cells or allogenic whole cell vaccines have progressed up to phase III trials. New drugs targeting bone microenvironment or apoptotic and proliferation pathways may enhance antitumour activity of chemotherapy in HRCP. Given the complexity of mechanisms underlying prostate cancer progression, future therapeutic strategies should rely on multidisciplinary approaches, thus exploiting newer molecular targets in concert with immunotherapy and cytotoxic chemotherapy. Here, we review the latest clinical evidence regarding the use of novel agents in HRPC.
Platinum-containing agents (cisplatin, carboplatin, oxaliplatin) are regarded as a high risk for ... more Platinum-containing agents (cisplatin, carboplatin, oxaliplatin) are regarded as a high risk for the development of hypersensitivity reactions. 1 Oxaliplatin is a third-generation organoplatinum compound in which the platinum atom is complexed with diaminocyclohexane and with an oxalate ligand. The drug has been approved for both second-line and first-line treatment of metastatic colorectal cancer (mCRC) in combination with 5-fluorouracil (5-FU) and leucovorin (LV), 2 and also for the adjuvant treatment of stage III CRC. 3 Oxaliplatin in combination with capecitabine has also used in a trial setting as preoperative chemoradiation in locally advanced rectal cancer. 3 Oxaliplatin is active in other malignancies, including gastric and pancreatic carcinomas. Its administration is especially convenient for patients and oncology departments because it is safely given in the outpatient setting. Widely used in a great variety of indications with various combinations of 5-FU/LV and capecitabine-based regimens, oxaliplatin is also combined with bevacizumab, an antineovasculature monoclonal antibody (MoAb) that binds to vascular endothelial growth factor. 2,4 The use of oxaliplatin has shown to have mild side effects ranging from reversible neurotoxicity and vomiting to manageable neutropenia and leukopenia. However, a significant percentage of patients receiving this chemotherapeutic agent might present idiosyncratic or hypersensitivity reactions (HSRs).
Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitab... more Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitabine is the accepted standard for the adjuvant and metastatic treatment of pancreatic cancer, however, it also has indications in breast, ovarian, and non-small cell lung cancers. The most common side effect is myelosuppression. Dyspnea is reported in 23% and bronchospasm occurs in less than 2% of subjects. Acute respiratory distress syndrome is rare with single agent use or in combination.
S-1 is an oral fluoropyrimidine that is designed to improve the antitumor activity of 5-fluoroura... more S-1 is an oral fluoropyrimidine that is designed to improve the antitumor activity of 5-fluorouracil (5-FU) concomitantly with an intent to reduce its toxicity. S-1 consists of tegafur, a prodrug of 5-FU combined with two 5-FU biochemical modulators:5-chloro-2,4-dihydroxypyridine (gimeracil or CDHP), a competitive inhibitor of dihydropyrimidine dehydrogenase and oteracil potassium which inhibits phosphorylation of 5-FU in the gastrointestinal tract decreasing serious gastrointestinal toxicities,including nausea, vomiting, stomatitis and diarrhea. Being an oral agent, S-1 offers convenience of administration and prevents complications of central venous access such as infection, thrombosis and bleeding. S-1 has shown efficacy in both gastrointestinal as well non-gastrointestinal malignancies. The authors review the current literature and provide their expert opinion on the incorporation of S-1 in the treatment of solid malignancies [corrected].
Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with sign... more Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with signs and symptoms inconsistent with known toxicity of antineoplastic drugs. These reactions are uncommon and usually associated with certain antineoplastic categories, such as taxanes, platinum-containing compounds, epipodofyllotoxins, asparaginase, procarbazine and, more rarely, with doxorubicin and 6-mercaptopurine. The mechanisms that are responsible for hypersensitivity reactions are unclear and vary between agents. Symptoms of these reactions range from mild skin rashes to more severe reactions, such as arthralgia, respiratory arrest or even death in some cases. Once hypersensitivity reactions are observed, basic principles that allow their management and possible continuance and completion of the regimen should be followed.
Although pancreatic carcinoma and depression have been linked for many years, the prevalence and ... more Although pancreatic carcinoma and depression have been linked for many years, the prevalence and relationship of these two entities are still poorly understood. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. If the definition of depression is broadened to include mild depression in addition to major depression, these numbers may increase. Depression in pancreatic cancer is a condition that must be diagnosed and treated, as studies have shown that depression is a detrimental factor in the last stages of life of cancer patients as patients with high score of depression have worse survival rates in breast and hepatobiliary cancers. Treatment for depression has also been shown to impact quality of life and may bring increased comfort during end of life. This article reviews the literature linking pancreatic carcinoma to depression as well as the appropriate therapeutic approach. In addition, for the first time, it fully underlines the key role of a social worker as a key participant throughout the cancer continuum: at time of diagnosis, treatment, relapse, survivorship, end of life and bereavement in the management of pancreatic cancer patients.
Heat shock proteins (HSP) play an essential role as molecular chaperones by assisting correct hol... more Heat shock proteins (HSP) play an essential role as molecular chaperones by assisting correct holding and folding in human cells. At the same time they present implications in tumor cell proliferation, differentiation, matrix invasion, angiogenesis, metastasis and cell death. They also possess the ability to present tumor molecules to the immune system and elicit an immune response. New agents targeting HSP, as anticancer treatment, are under clinical evaluation. The aim of this review is to explore the role of HSP90 inhibitors as anticancer agents as well as to evaluate the benefit from the use of autologous HSP vaccines in both the adjuvant setting and first-line treatment. The latest evidence regarding the use of geldanamycin analogues or newer water-soluble and synthetics molecules that inhibit the binding of HSP90 to client proteins was reviewed. Immunization using tumor-derived HSP in several cancer types was also evaluated. HSP90 inhibitors represent a promising therapeutic option although further evaluation in larger clinical trials is needed. On the other hand, HSP vaccination has already an established role in our armory against cancer.
Pancreatic cancer is a deadly malignancy with still high mortality and poor survival despite the ... more Pancreatic cancer is a deadly malignancy with still high mortality and poor survival despite the significant advances in understanding, diagnosis, and access to conventional and novel treatments. Though cytotoxic chemotherapy based on the purine analogue gemcitabine remains the standard approach in adjuvant and palliative setting the need for novel agents aiming at the main pathophysiological abnormalities and molecular pathways involved remains soaring. So far, evidence of clinical benefit, though small, exists only from the addition of the targeted agent erlotinib on the standard gemcitabine chemotherapy. Apart from the popular monoclonal antibodies and small molecules tyrosine kinase inhibitors, other novel compounds being tested in preclinical and clinical studies target mTOR, NF-κB, proteasome and histone deacetylase. These new drugs along with gene therapy and immunotherapy, which are also under clinical evaluation, may alter the unfavorable natural course of this disease. In this review we present the main pathophysiological alterations met in pancreatic cancer and the results of the florid preclinical and clinical research with regards to the targeted therapy associated to these abnormalities.
Autoimmunity can be associated with cancer and one of the forms of its expression is the developm... more Autoimmunity can be associated with cancer and one of the forms of its expression is the development of antibodies to autologous cellular antigens. The types of cellular proteins which induce autoantibody responses in gastrointestinal malignancies are quite varied and include cellular proteins encoded by mutated normal genes (p53), cellular proteins that are overexpressed and/or aberrantly expressed in malignant tissues (carcinoembryonic antigen), inhibitors of apoptosis (survivin and livin), major components of mucus (mucins), surface receptors of apoptosis (Fas) and nuclear-restricted proteins (double-stranded DNA, single-stranded DNA and Sm family proteins). In the past few years, due to the great clinical interest and the advancement in detection techniques, the above list has grown significantly and a large number of cancer-related antigens, which trigger a specific humoral immune response to the host, have also been identified. The authors review the autoantibodies associated with gastrointestinal malignancies and their clinical implications.
The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and ... more The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.
Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, app... more Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, approved as first line treatment concurrently administrated with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer. One of the most common side effects, rash, is possibly linked to overall and progression-free survival and may serve as a potential surrogate marker. Nevertheless, erlotinib-induced rash is cause of negative impact on patients' quality of life and often can trigger discontinuation of treatment. Adequate and timely management of rash depending on the grade of rash is important for therapy continuation.
Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is c... more Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.
Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing... more Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing ones. Multiple molecules regulate angiogenesis, such as the vascular endothelial growth factor, angiopoietins, the fibroblast growth factor, the platelet-derived growth factor and the transforming growth factor-β. Angiogenesis plays an important role in the growth, progression and metastasis of a tumour. Inhibiting the angiogenic process or targeting existing tumour vessels can be used for treatment of tumours as an alternative or in parallel with conventional chemotherapy. Many anti-angiogenic factors are under investigation and some are already being used in clinical practice with various results.
Autoimmunity can be associated with cancer and one of the forms of its expression is the developm... more Autoimmunity can be associated with cancer and one of the forms of its expression is the development of antibodies to autologous cellular antigens. The types of cellular proteins which induce autoantibody responses in gastrointestinal malignancies are quite varied and include cellular proteins encoded by mutated normal genes (p53), cellular proteins that are overexpressed and/or aberrantly expressed in malignant tissues (carcinoembryonic antigen), inhibitors of apoptosis (survivin and livin), major components of mucus (mucins), surface receptors of apoptosis (Fas) and nuclear-restricted proteins (double-stranded DNA, single-stranded DNA and Sm family proteins). In the past few years, due to the great clinical interest and the advancement in detection techniques, the above list has grown significantly and a large number of cancer-related antigens, which trigger a specific humoral immune response to the host, have also been identified. The authors review the autoantibodies associated with gastrointestinal malignancies and their clinical implications.
The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and ... more The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.
Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, app... more Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, approved as first line treatment concurrently administrated with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer. One of the most common side effects, rash, is possibly linked to overall and progression-free survival and may serve as a potential surrogate marker. Nevertheless, erlotinib-induced rash is cause of negative impact on patients' quality of life and often can trigger discontinuation of treatment. Adequate and timely management of rash depending on the grade of rash is important for therapy continuation.
Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is c... more Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.
Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing... more Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing ones. Multiple molecules regulate angiogenesis, such as the vascular endothelial growth factor, angiopoietins, the fibroblast growth factor, the platelet-derived growth factor and the transforming growth factor-β. Angiogenesis plays an important role in the growth, progression and metastasis of a tumour. Inhibiting the angiogenic process or targeting existing tumour vessels can be used for treatment of tumours as an alternative or in parallel with conventional chemotherapy. Many anti-angiogenic factors are under investigation and some are already being used in clinical practice with various results.
The diagnosis of pancreatic cancer is devastating for patients and their relatives as the inciden... more The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease. Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.
Prostate cancer is one of the leading causes of cancer related death in men, and remains incurabl... more Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC). In an attempt to improve survival benefit, several novel drugs targeting specific pathways involved in cell signaling, proliferation, angiogenesis, apoptosis and immune modulation are currently under investigation either as single agents or in combination with cytotoxic drugs. Clinical trials evaluate the inhibition of prostate cancer cells growth by targeting the nuclear receptor of vitamin D alongside cytotoxic therapy. Angiogenesis inhibitors as well as epidermal growth factor receptor blockage are also under clinical investigation in several combinations. Immunomodulatory agents and autologous dendritic cells or allogenic whole cell vaccines have progressed up to phase III trials. New drugs targeting bone microenvironment or apoptotic and proliferation pathways may enhance antitumour activity of chemotherapy in HRCP. Given the complexity of mechanisms underlying prostate cancer progression, future therapeutic strategies should rely on multidisciplinary approaches, thus exploiting newer molecular targets in concert with immunotherapy and cytotoxic chemotherapy. Here, we review the latest clinical evidence regarding the use of novel agents in HRPC.
Platinum-containing agents (cisplatin, carboplatin, oxaliplatin) are regarded as a high risk for ... more Platinum-containing agents (cisplatin, carboplatin, oxaliplatin) are regarded as a high risk for the development of hypersensitivity reactions. 1 Oxaliplatin is a third-generation organoplatinum compound in which the platinum atom is complexed with diaminocyclohexane and with an oxalate ligand. The drug has been approved for both second-line and first-line treatment of metastatic colorectal cancer (mCRC) in combination with 5-fluorouracil (5-FU) and leucovorin (LV), 2 and also for the adjuvant treatment of stage III CRC. 3 Oxaliplatin in combination with capecitabine has also used in a trial setting as preoperative chemoradiation in locally advanced rectal cancer. 3 Oxaliplatin is active in other malignancies, including gastric and pancreatic carcinomas. Its administration is especially convenient for patients and oncology departments because it is safely given in the outpatient setting. Widely used in a great variety of indications with various combinations of 5-FU/LV and capecitabine-based regimens, oxaliplatin is also combined with bevacizumab, an antineovasculature monoclonal antibody (MoAb) that binds to vascular endothelial growth factor. 2,4 The use of oxaliplatin has shown to have mild side effects ranging from reversible neurotoxicity and vomiting to manageable neutropenia and leukopenia. However, a significant percentage of patients receiving this chemotherapeutic agent might present idiosyncratic or hypersensitivity reactions (HSRs).
Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitab... more Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitabine is the accepted standard for the adjuvant and metastatic treatment of pancreatic cancer, however, it also has indications in breast, ovarian, and non-small cell lung cancers. The most common side effect is myelosuppression. Dyspnea is reported in 23% and bronchospasm occurs in less than 2% of subjects. Acute respiratory distress syndrome is rare with single agent use or in combination.
S-1 is an oral fluoropyrimidine that is designed to improve the antitumor activity of 5-fluoroura... more S-1 is an oral fluoropyrimidine that is designed to improve the antitumor activity of 5-fluorouracil (5-FU) concomitantly with an intent to reduce its toxicity. S-1 consists of tegafur, a prodrug of 5-FU combined with two 5-FU biochemical modulators:5-chloro-2,4-dihydroxypyridine (gimeracil or CDHP), a competitive inhibitor of dihydropyrimidine dehydrogenase and oteracil potassium which inhibits phosphorylation of 5-FU in the gastrointestinal tract decreasing serious gastrointestinal toxicities,including nausea, vomiting, stomatitis and diarrhea. Being an oral agent, S-1 offers convenience of administration and prevents complications of central venous access such as infection, thrombosis and bleeding. S-1 has shown efficacy in both gastrointestinal as well non-gastrointestinal malignancies. The authors review the current literature and provide their expert opinion on the incorporation of S-1 in the treatment of solid malignancies [corrected].
Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with sign... more Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with signs and symptoms inconsistent with known toxicity of antineoplastic drugs. These reactions are uncommon and usually associated with certain antineoplastic categories, such as taxanes, platinum-containing compounds, epipodofyllotoxins, asparaginase, procarbazine and, more rarely, with doxorubicin and 6-mercaptopurine. The mechanisms that are responsible for hypersensitivity reactions are unclear and vary between agents. Symptoms of these reactions range from mild skin rashes to more severe reactions, such as arthralgia, respiratory arrest or even death in some cases. Once hypersensitivity reactions are observed, basic principles that allow their management and possible continuance and completion of the regimen should be followed.
Although pancreatic carcinoma and depression have been linked for many years, the prevalence and ... more Although pancreatic carcinoma and depression have been linked for many years, the prevalence and relationship of these two entities are still poorly understood. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. If the definition of depression is broadened to include mild depression in addition to major depression, these numbers may increase. Depression in pancreatic cancer is a condition that must be diagnosed and treated, as studies have shown that depression is a detrimental factor in the last stages of life of cancer patients as patients with high score of depression have worse survival rates in breast and hepatobiliary cancers. Treatment for depression has also been shown to impact quality of life and may bring increased comfort during end of life. This article reviews the literature linking pancreatic carcinoma to depression as well as the appropriate therapeutic approach. In addition, for the first time, it fully underlines the key role of a social worker as a key participant throughout the cancer continuum: at time of diagnosis, treatment, relapse, survivorship, end of life and bereavement in the management of pancreatic cancer patients.
Heat shock proteins (HSP) play an essential role as molecular chaperones by assisting correct hol... more Heat shock proteins (HSP) play an essential role as molecular chaperones by assisting correct holding and folding in human cells. At the same time they present implications in tumor cell proliferation, differentiation, matrix invasion, angiogenesis, metastasis and cell death. They also possess the ability to present tumor molecules to the immune system and elicit an immune response. New agents targeting HSP, as anticancer treatment, are under clinical evaluation. The aim of this review is to explore the role of HSP90 inhibitors as anticancer agents as well as to evaluate the benefit from the use of autologous HSP vaccines in both the adjuvant setting and first-line treatment. The latest evidence regarding the use of geldanamycin analogues or newer water-soluble and synthetics molecules that inhibit the binding of HSP90 to client proteins was reviewed. Immunization using tumor-derived HSP in several cancer types was also evaluated. HSP90 inhibitors represent a promising therapeutic option although further evaluation in larger clinical trials is needed. On the other hand, HSP vaccination has already an established role in our armory against cancer.
Pancreatic cancer is a deadly malignancy with still high mortality and poor survival despite the ... more Pancreatic cancer is a deadly malignancy with still high mortality and poor survival despite the significant advances in understanding, diagnosis, and access to conventional and novel treatments. Though cytotoxic chemotherapy based on the purine analogue gemcitabine remains the standard approach in adjuvant and palliative setting the need for novel agents aiming at the main pathophysiological abnormalities and molecular pathways involved remains soaring. So far, evidence of clinical benefit, though small, exists only from the addition of the targeted agent erlotinib on the standard gemcitabine chemotherapy. Apart from the popular monoclonal antibodies and small molecules tyrosine kinase inhibitors, other novel compounds being tested in preclinical and clinical studies target mTOR, NF-κB, proteasome and histone deacetylase. These new drugs along with gene therapy and immunotherapy, which are also under clinical evaluation, may alter the unfavorable natural course of this disease. In this review we present the main pathophysiological alterations met in pancreatic cancer and the results of the florid preclinical and clinical research with regards to the targeted therapy associated to these abnormalities.
Autoimmunity can be associated with cancer and one of the forms of its expression is the developm... more Autoimmunity can be associated with cancer and one of the forms of its expression is the development of antibodies to autologous cellular antigens. The types of cellular proteins which induce autoantibody responses in gastrointestinal malignancies are quite varied and include cellular proteins encoded by mutated normal genes (p53), cellular proteins that are overexpressed and/or aberrantly expressed in malignant tissues (carcinoembryonic antigen), inhibitors of apoptosis (survivin and livin), major components of mucus (mucins), surface receptors of apoptosis (Fas) and nuclear-restricted proteins (double-stranded DNA, single-stranded DNA and Sm family proteins). In the past few years, due to the great clinical interest and the advancement in detection techniques, the above list has grown significantly and a large number of cancer-related antigens, which trigger a specific humoral immune response to the host, have also been identified. The authors review the autoantibodies associated with gastrointestinal malignancies and their clinical implications.
The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and ... more The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.
Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, app... more Erlotinib is a tyrosine kinase inhibitor with anti epidermal growth factor receptor activity, approved as first line treatment concurrently administrated with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer. One of the most common side effects, rash, is possibly linked to overall and progression-free survival and may serve as a potential surrogate marker. Nevertheless, erlotinib-induced rash is cause of negative impact on patients' quality of life and often can trigger discontinuation of treatment. Adequate and timely management of rash depending on the grade of rash is important for therapy continuation.
Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is c... more Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.
Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing... more Angiogenesis is the physiological process of the formation of new blood vessels from pre-existing ones. Multiple molecules regulate angiogenesis, such as the vascular endothelial growth factor, angiopoietins, the fibroblast growth factor, the platelet-derived growth factor and the transforming growth factor-β. Angiogenesis plays an important role in the growth, progression and metastasis of a tumour. Inhibiting the angiogenic process or targeting existing tumour vessels can be used for treatment of tumours as an alternative or in parallel with conventional chemotherapy. Many anti-angiogenic factors are under investigation and some are already being used in clinical practice with various results.
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