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1.
Cureus ; 16(2): e55040, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38550439

ABSTRACT

Apixaban is a rare cause of drug-induced leukocytoclastic vasculitis (LCV). We report a case of apixaban-induced LCV in a 55-year-old male with deep vein thrombosis who developed systemic symptoms and pruritic rash in the bilateral lower extremity after 17 days of apixaban therapy. A skin biopsy confirmed the LCV, and he was diagnosed with apixaban-induced LCV after ruling out all other possible causes. His condition improved after apixaban discontinuation, supportive management, and oral prednisone. Our case highlights the early diagnosis and management of drug-induced LCV and also describes the existing literature to highlight existing knowledge and potential mechanisms underlying anticoagulant-induced vasculitis.

2.
Curr Oncol Rep ; 26(1): 1-9, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38091201

ABSTRACT

PURPOSE OF REVIEW: HER2-positive breast cancer accounts for 10-15% of all breast cancers and fam-trastuzumab deruxtecan (T-DXd) has played a major role in moving the treatment of HER2-expressing disease forward. RECENT FINDINGS: T-DXd is a novel antibody-drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody against HER2 receptor bound to a potent topoisomerase I cytotoxin payload by a cleavable peptide linker. It has been shown to have robust preclinical activity in pretreated cancer cell lines, as well as meaningful clinical activity in advanced HER2-expressing breast cancer. Recent studies have demonstrated T-DXd as an active agent for metastatic HER2-positive patients, and as a viable additional line for heavily pretreated patients with HER2-low disease. The toxicity of T-DXd remains manageable and burden of side effects seems to be lower when offered as an earlier line of therapy over the course of treatment. In this review, we discuss the pharmacology of T-DXd, review pertinent preclinical and clinical data, and address potential challenges and future directions related to the use of T-DXd in clinical practice.


Subject(s)
Breast Neoplasms , Camptothecin/analogs & derivatives , Immunoconjugates , Humans , Female , Receptor, ErbB-2/metabolism , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Camptothecin/pharmacology , Camptothecin/therapeutic use , Immunoconjugates/pharmacology , Immunoconjugates/therapeutic use , Breast Neoplasms/pathology , Antibodies, Monoclonal, Humanized/therapeutic use
3.
Expert Rev Anticancer Ther ; 23(10): 1085-1093, 2023.
Article in English | MEDLINE | ID: mdl-37750222

ABSTRACT

INTRODUCTION: Triple negative breast cancer (TNBC) is a rare but aggressive biological subtype of breast cancer associated with higher locoregional and distant recurrence rates and lower overall survival despite advancements in diagnostic and treatment strategies. AREAS COVERED: This review explores the evolving landscape of locoregional recurrence (LRR) in TNBC with improved surgical and radiation therapy delivery techniques including salvage breast conserving surgery (SBCS), re-irradiation, and thermo-radiation. We review current retrospective and prospective, albeit limited, clinical data highlighting the optimal management of locoregionally recurrent TNBC. We also discuss tumor genomic profiling and transcriptome analysis and review potential investigational directions. EXPERT OPINION: Significant progress has been made in the prevention of LRR but rates remain suboptimal, particularly in the TNBC population, and outcomes following LRR are poor. Further prospective studies are needed to identify the most effective and safest systemic therapy regimens and to whom it should be offered. There has been growing interest in the role of molecular markers, genomic signatures, and tumor microenvironment in predicting outcomes and guiding LRR treatment. Transcriptome analyses and biomarker-driven investigations are currently being studied and represent a promising era of development in the management of LRR.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/therapy , Breast Neoplasms/pathology , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Mastectomy, Segmental , Prospective Studies , Tumor Microenvironment
4.
Cureus ; 15(3): e36039, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37056547

ABSTRACT

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially devastating blood disorder depicted by thrombocytopenia, fever, widespread small vessel hemolytic anemia, and neurological symptoms. The involvement of the renal and neurological systems is frequently reported in TTP; however, TTP-induced acute coronary syndrome is not widely reported. We describe a case of myocardial infarction induced by TTP in a patient who presented with the typical manifestation of acute coronary syndrome. Echocardiogram revealed a myocardial injury, and detailed investigations revealed increased levels of troponin I, lactate dehydrogenase, diminished levels of haptoglobin and von Willebrand factor-cleaving protease, and schistocytes on peripheral smear, suggestive of TTP-induced myocardial infarction. His condition was stabilized after commencing plasmapheresis, steroids, and rituximab. The initial steps in the management of this patient involve the prompt administration of steroids and the urgent start of plasmapheresis to increase platelet count.

5.
Cureus ; 15(2): e34550, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36879697

ABSTRACT

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the adenoviral vector COVID-19 vaccine is a rare adverse event. Although the risk of VITT following the COVID-19 vaccine appears to be low, early diagnosis and management can be lifesaving. We present a case of VITT in a young female who presented with persistent headaches and fevers followed by anisocoria and right-sided hemiplegia. Initial imaging was unremarkable, and labs showed thrombocytopenia and elevated d-dimers. Repeat imaging revealed thrombosis in the left transverse and superior sagittal sinuses, and she was diagnosed with VITT. She received combined treatment with intravenous immunoglobulins and systemic anticoagulation, resulting in an increased platelet count and resolution of her neurological symptoms.

6.
Future Oncol ; 2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36399037

ABSTRACT

Immune checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not clinically effective in immunogenically 'cold' tumors such as pancreatic cancer, prostate cancer and neuroendocrine tumors. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade in tumors that have traditionally shown a lack of clinical response to immunotherapy. This signal-seeking, single-arm, prospective clinical trial aims to determine the objective response of tivozanib and atezolizumab in advanced immunogenically cold solid tumors. Clinical Trial Registration: NCT05000294 (ClinicalTrials.gov).

7.
Cancer Treat Rev ; 105: 102376, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35303547

ABSTRACT

As cancer treatment evolves in the era of precision oncology, molecularly targeted agents (MTAs) have become frontline therapy for many cancers. MTAs are biologically targeted and thought to have less off-target toxicity; however, the eye is particularly susceptible to off-target toxicities given its unique microenvironment. In this review, we present commonly used FDA-approved MTAs, any associated ocular toxicities and review the mechanisms, frequency, severity, and management. Increased awareness and communication between clinicians caring for cancer patients is needed for individualized risk assessment, earlier diagnosis, and mitigation of ocular toxicities.


Subject(s)
Antineoplastic Agents , Neoplasms , Oncologists , Antineoplastic Agents/therapeutic use , Humans , Molecular Targeted Therapy , Neoplasms/drug therapy , Precision Medicine , Tumor Microenvironment
8.
Breast Cancer Res Treat ; 192(3): 491-499, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35142938

ABSTRACT

PURPOSE: Breast cancer in men (BC-M) is almost exclusively hormone receptor positive. We conducted a large review of the SEER-Medicare linked database to compare endocrine therapy adherence, discontinuation, and survival outcomes of male versus female patients with breast cancer. METHODS: Study data were obtained through the SEER-Medicare linked database. The study included patients age ≥ 65 years-old diagnosed with breast cancer between 2007 and 2015. The primary endpoints were rates of adherence and discontinuation of endocrine therapy (ET). Adherence was defined as a gap of less than 90 days in-between consecutive Medicare prescriptions. Discontinuation was defined as a gap of greater than 12 months in-between Medicare prescriptions. Secondary endpoint was the association of use of ET with overall survival (OS). RESULTS: Of the 363 male patients on ET, 214 patients (59.0%) were adherent to the therapy, and 149 patients (41.0%) were nonadherent. Of the 20,722 females on ET, 10,752 (51.9%) were adherent to the therapy, and 9970 (48.1%) were nonadherent. 39 male patients (10.7%) discontinued therapy, while 324 (89.3%) did not discontinue therapy. 1849 female patients (8.9%) discontinued therapy, while 18,873 (91.1%) patients did not. Men were significantly more adherent than women (p = 0.008), but there was no significant difference in discontinuation among men and women (p = 0.228). Survival was significantly improved in both men (HR 0.77, 95% CI 0.60-0.99, p = 0.039) and women (HR 0.84, 95% CI 0.81-0.87, p < 0.001) on ET. CONCLUSION: Identification of contributing factors impacting adherence and discontinuation is needed to allow physicians to address barriers to long term use of ET.


Subject(s)
Breast Neoplasms , Aged , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Female , Humans , Male , Medicare , Medication Adherence , SEER Program , United States/epidemiology
9.
Cureus ; 13(9): e18255, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34712532

ABSTRACT

Introduction Vitamin D is responsible for regulating innate and adaptive immune responses and for boosting the immune system; hence, a decline in its levels results in autoimmunity. Current studies have linked the deficiency of vitamin D to different autoimmune diseases, including rheumatoid arthritis (RA). In this study, we will determine the association between vitamin D level and RA. Methods This is a case-control study, conducted in a tertiary care hospital in Pakistan from January 2021 to May 2021. Three hundred patients with a confirmed recent diagnosis of RA were enrolled as the study group. Another 300 participants without RA, matched for age and gender, were enrolled in the study as a control group. RA was diagnosed on the basis of clinical symptoms, radiological features on X-ray, and anti-citrullinated protein levels of more than 20 u/mL. Results The mean vitamin D level in participants with RA was significantly lower than in the placebo group (30.18 ± 6.27 vs. 38.29 ± 7.98; p-value: <0.0001). The mean vitamin D level in participants with positive RF patients was significantly lower compared to rheumatoid factor (RF)-negative RA patients (29.21 ± 5.16 vs. 32.26 ± 7.02; p-value: <0.0001). There were more participants with hypovitaminosis D in RF-positive participants as compared to RF negative (88.6% vs. 44.3%; p-value: 0.00001). Conclusion There is a high prevalence of vitamin D deficiency in patients with RA and there is a link with disease severity. Therefore, a high index of suspicion is required while evaluating the at-risk patients, especially women, with complaints of vitamin D deficiency. Vitamin D supplementation may be needed for the prevention or avoidance of the progression of the disease.

10.
Cureus ; 13(6): e15716, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34295575

ABSTRACT

Introduction Patients with rheumatoid arthritis (RA) have a higher risk of cardiovascular diseases (CVDs) when compared to the general population, with most deaths attributed to myocardial infarctions (MI). However, patients with RA do not get the same attention in terms of cardiovascular screening as compared to other diseases, like diabetes mellitus (DM). Therefore, this study aims to compare the risk of CVD among patients with RA and DM. Methods This prospective study was carried out in Pakistan's two tertiary care hospitals. A total of 750 participants were enrolled in three groups with a 1:1:1 ratio; patients with RA, type 2 DM, and the control group. Patients were observed for 12 months or until the development of a major adverse cardiovascular event (MACE), whichever occurred first. Results Both fatal (12.66% vs. 13.48%; p-value: 0.79) and non-fatal (3.93% vs. 4.35%; p-value: 0.82) MI was comparable between both RA and DM group. However, compared to the control group, non-fatal MI (12.66% vs. 5.58%; p-value: 0.01) was significantly higher in the RA group. Conclusion Our study shows that RA and DM have an equal risk of cardiovascular (CV) events. It is important that RA should be considered as a prominent risk factor for CV events. The management of these patients should be multidisciplinary, including cardiologists.

11.
Oncologist ; 26(10): 825-e1674, 2021 10.
Article in English | MEDLINE | ID: mdl-34101295

ABSTRACT

LESSONS LEARNED: Preclinical studies have demonstrated that Src inhibition through dasatinib synergistically enhances the antitumor effects of oxaliplatin. In this phase II, single-arm study, FOLFOX with dasatinib in previously untreated patients with mPC only showed only modest clinical activity, with a progressive-free survival of 4 months and overall survival of 10.6 months. Continued investigation is ongoing to better understand the role of Src inhibition with concurrent 5-fluorouracil and oxaliplatin in a subset of exceptional responders. BACKGROUND: Src tyrosine kinase activity is overexpressed in many human cancers, including metastatic pancreatic cancer (mPC). Dasatinib is a potent inhibitor of Src family of tyrosine kinases. This study was designed to investigate whether dasatinib can synergistically enhance antitumor effects of FOLFOX regimen (FOLFOX-D). METHODS: In this single-arm, phase II study, previously untreated patients received dasatinib 150 mg oral daily on days 1-14, oxaliplatin 85 mg/m2 intravenous (IV) on day 1 every 14 days, leucovorin (LV) 400 mg/m2 IV on day 1 every 14 days, 5-fluorouracil (5-FU) bolus 400 mg/m2 on day 1 every 14 days, and 5-FU continuous infusion 2,400 mg/m2 on day 1 every 14 days. Primary endpoint was progression-free survival (PFS) with preplanned comparison to historical controls. RESULTS: Forty-four patients enrolled with an estimated median PFS of 4.0 (95% confidence interval [CI], 2.3-8.5) months and overall survival (OS) of 10.6 (95% CI, 6.9-12.7) months. Overall response rate (ORR) was 22.7% (n = 10): one patient (2.3%) with complete response (CR) and nine patients (20.5%) with partial response (PR). Fifteen patients (34.1%) had stable disease (SD). Nausea was the most common adverse event (AE) seen in 35 patients (79.5%). CONCLUSION: The addition of dasatinib did not appear to add incremental clinical benefit to FOLFOX in untreated patients with mPC.


Subject(s)
Adenocarcinoma , Colorectal Neoplasms , Pancreatic Neoplasms , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Dasatinib/pharmacology , Dasatinib/therapeutic use , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Pancreatic Neoplasms/drug therapy , Treatment Outcome
12.
Cureus ; 13(4): e14712, 2021 Apr 27.
Article in English | MEDLINE | ID: mdl-34055551

ABSTRACT

Background Cluster of differentiation 26/dipeptidyl peptidase-4 (DPP4) is a cell surface glycoprotein with multifaceted roles, including immune regulation, glucose metabolism, and tumorigenesis. Recent literature has identified DPP4 inhibitors to improve survival in diabetic patients with prostate cancer. DPP4 inhibitors have been proposed to play a role in prostate cancer, as DPP4 is found at higher levels in malignant prostate tissue compared to benign and correlates with PSA levels and cancer stage. In this multi-center retrospective study, we aim to define the effects of DPP4 inhibitors on progression-free survival (PFS) in diabetic patients with advanced-stage prostate cancer. Methodology We performed a retrospective analysis of 161 patients with diabetes and advanced-stage (III or IV) prostate cancer at the University of Florida Health Cancer Center and Moffitt Cancer Center. Our cohort included 120 patients on metformin (control group) and 41 on a DPP4 inhibitor (study group). Results No significant difference in progression of prostate cancer was identified between those on DPP4 inhibitors versus metformin (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.64-1.61; p = 0.955). Median time to progression was 3.5 years (range: 2.4-4.6 years). Conclusions Despite prior literature indicating survival benefit of DPP4 inhibitors in prostate cancer, our study did not identify a statistically significant improvement of PFS in diabetic patients with advanced prostate cancer. Additional analysis with larger sample sizes and prospective investigation with study of tumor microenvironment are needed to evaluate clinical impact and potential survival benefit of DPP4 inhibitors in prostate cancer.

13.
Oncologist ; 26(5): 362-e724, 2021 05.
Article in English | MEDLINE | ID: mdl-33512054

ABSTRACT

LESSONS LEARNED: Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance. In this single-arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression-free survival of 6.2 months with an acceptable toxicity profile. This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC. BACKGROUND: Capecitabine (Cape) is an oral prodrug of the antimetabolite 5-fluorouracil. Sorafenib (Sor) inhibits multiple signaling pathways involved in angiogenesis and tumor proliferation. SorCape has been previously studied in metastatic breast cancer. METHODS: This single-arm, phase II study was designed to evaluate the activity of SorCape in refractory metastatic colorectal cancer (mCRC). Patients received Sor (200 mg p.o. b.i.d. max daily) and Cape (1,000 mg/m2 p.o. b.i.d. on days 1-14) on a 21-day treatment cycle. Primary endpoint was progression-free survival (PFS) with preplanned comparison with historical controls. RESULTS: Forty-two patients were treated for a median number of 3.5 cycles (range 1-39). Median PFS was 6.2 (95% confidence interval [CI], 4.3-7.9) months, and overall survival (OS) was 8.8 (95% CI, 4.3-12.2) months. One patient (2.4%) had partial response (PR), and 22 patients (52.4%) had stable disease (SD) for a clinical benefit rate of 54.8% (95% CI, 38.7%-70.2%). Hand-foot syndrome was the most common adverse event seen in 36 patients (85.7%) and was grade ≥ 3 in 16 patients (38.1%). One patient (2.4%) had a grade 4 sepsis, and one patient (2.4%) died while on treatment. CONCLUSION: SorCape in this heavily pretreated population yielded a reasonable PFS with manageable but notable toxicity. The combination should be investigated further.


Subject(s)
Colorectal Neoplasms , Deoxycytidine , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/therapeutic use , Colorectal Neoplasms/drug therapy , Deoxycytidine/therapeutic use , Fluorouracil/therapeutic use , Humans , Sorafenib/therapeutic use , Treatment Outcome
14.
Front Oncol ; 10: 405, 2020.
Article in English | MEDLINE | ID: mdl-32296640

ABSTRACT

Background: Dipeptidyl peptidase-4 (DPP4), a cell surface protein, exhibits a crucial role in tumor biology and regulation of the immune system. We aim to study the impact of DPP4 inhibitors (DPP4i) in patients with prostate cancer (PRC), pancreatic cancer (PC) and breast cancer (BC). Methods: Using the SEER and Medicare linked database, we identified patients with PRC or PC or BC with coexisting type II diabetes mellitus between 2007 and 2015. Patients were classified into four groups: (1) not on either DPP4i or metformin (reference group), this group included patient that were on anti-diabetic agents other than metformin or DPP4i (2) metformin only, (3) DPP4i only, and (4) DPP4i along with metformin (combination group). Overall survival (OS) analyses were performed using SAS®, version 9.4. Results: We identified 15,330 patients with PRC, 5,359 patients with PC and 16,085 patients with BC. In PRC cohort, patients on DPP4i had significant survival advantage with HR 0.77 (95% CI: 0.64-0.93), P = 0.005 when compared to the reference group. Patients taking metformin also had significant OS benefit with HR 0.87 (95% CI: 0.81-0.93), P < 0.0001 when compared to the reference group. However, in BC cohort, OS did not favor the patients taking DPP4i with HR 1.07 (95% CI: 0.93-1.25, P = 0.33). Similarly, in PC cohort, OS was indifferent for the patients on DPP4i with HR 1.07 (95% CI: 0.93-1.24, P = 0.68). Upon subgroup analyses of PRC patients, the survival favored the group taking DPP4i, irrespective of stage, use of chemotherapy, androgen-deprivation therapy, and prostatectomy or radiation therapy. Conclusions: DPP4i seems to improve survival in PRC patients; however, not in PC or BC patients. While the exact mechanism involved remains to be elucidated, a prospective clinical trial would help to confirm these findings.

15.
J Chem Ecol ; 46(3): 330-343, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31989490

ABSTRACT

Plants perceive insect herbivores via a sophisticated surveillance system that detects a range of alarm signals, including herbivore-associated molecular patterns (HAMPs). Fatty acid-amino acid conjugates (FACs) are HAMPs present in oral secretions (OS) of lepidopteran larvae that induce defense responses in many plant species. In contrast to eggplant (Solanum melongena), tomato (S. lycopersicum) does not respond to FACs present in OS from Manduca sexta (Lepidoptera). Since both plants are found in the same genus, we tested whether loss of sensitivity to FACs in tomato may be a domestication effect. Using highly sensitive MAP kinase (MAPK) phosphorylation assays, we demonstrate that four wild tomato species and the closely related potato (S. tuberosum) do not respond to the FACs N-linolenoyl-L-glutamine and N-linolenoyl-L-glutamic acid, excluding a domestication effect. Among other genera within the Solanaceae, we found that bell pepper (Capsicum annuum) is responsive to FACs, while there is a differential responsiveness to FACs among tobacco (Nicotiana) species, ranging from strong responsiveness in N. benthamiana to no responsiveness in N. knightiana. The Petunia lineage is one of the oldest lineages within the Solanaceae and P. hybrida was responsive to FACs. Collectively, we demonstrate that plant responsiveness to FACs does not follow simple phylogenetic relationships in the family Solanaceae. Instead, sensitivity to FACs is a dynamic ancestral trait present in monocots and eudicots that was repeatedly lost during the evolution of Solanaceae species. Although tomato is insensitive to FACs, we found that other unidentified factors in M. sexta OS induce defenses in tomato.


Subject(s)
Amino Acids/metabolism , Antibiosis , Fatty Acids/metabolism , Herbivory , Manduca/physiology , Solanaceae/physiology , Animals , Larva , Species Specificity
16.
Cureus ; 11(4): e4552, 2019 Apr 27.
Article in English | MEDLINE | ID: mdl-31275776

ABSTRACT

Introduction Multiple primary malignancies (MPMs) are seen in ~5% of all tumors. The aim of this study was to determine the quantitative impact on overall survival (OS) and treatment choices in patients with MPMs. Methods A retrospective analysis to determine patients with MPMs was conducted over a six-year period. Patients were defined as simultaneous MPMs if the second malignancy was discovered within 60 days of the first, and as sequential MPMs if discovered after 60 days of the first. Results Fifty-six patients with MPMs as defined above were identified, 38 (68%) simultaneous and 18 (32%) sequential. Development of second malignancy did not affect treatment in 47 (84%) of patients. Median OS after diagnosis of first malignancy was 13.0 months (95% confidence interval (CI) 10.3-15.8 months), compared to 10.6 months (95% CI 7.1-13.9 months) after the diagnosis of second malignancy. Median OS for the simultaneous MPM group was 13.5 months (95% CI 7.1-19.9 months), compared to 3.2 months (95% CI 0.0-9.8 months) for the sequential MPM group. Conclusions The development of a second malignancy impacts OS and treatment decisions. Patients who developed sequential MPM performed poorer than those who developed simultaneous MPM. This was likely in part due to effects of existing treatment on performance status as well as treatment preferences when second MPM is diagnosed (as many patients opted for supportive care after second MPM). Further analysis with larger patient cohorts is necessary to ascertain the aforementioned effects of OS and treatment options with respect to tumor pathology, stage, and performance status.

17.
Cancer Med ; 8(8): 3918-3927, 2019 07.
Article in English | MEDLINE | ID: mdl-31124302

ABSTRACT

BACKGROUND: Dipeptidyl peptidase 4 (DPP4) is a cell surface protein that can act as a tumor suppressor or activator, depending upon the level of expression and interaction with the microenvironment and chemokines. DPP4 inhibitors are used to treat diabetes. METHODS: We conducted this Surveillance Epidemiology and Endpoint Research-Medicare database study to evaluate the role of DPP4 inhibitors on the overall survival (OS) of diabetic patients diagnosed with colorectal (CRC) and lung cancers. RESULTS: Diabetic patients with CRC or lung cancer who were treated with DPP4 inhibitors exhibited a statistically significant survival advantage (hazard ratio [HR] of 0.89; CI: 0.82-0.97, P = 0.007) that remained significant after controlling for all other confounders. When DPP4 inhibitors were used in combination of metformin which is known to suppress cancer, the survival advantage was even more pronounced (HR of 0.83; CI: 0.77-0.90, P < 0.0001). Data were then analyzed separately for two cancer types. In the CRC-only cohort, the use of DPP4 inhibitors alone had a positive trend but did not meet statistically significant threshold (HR of 0.87; CI: 0.75-1.00, P = 0.055), while the combined use of DPP4 inhibitors and metformin was associated with statistically significant survival advantage (HR of 0.77; CI: 0.67-0.89, P = 0.003). Similarly, for the lung cancer cohort, use of DPP4 alone was not found to be statistically significant (HR of 0.93; CI: 0.83-1.03, P = 0.153), whereas lung cancer patients treated with the combination of DPP4 inhibitors and metformin showed statistically significant survival advantage (HR of 0.88; CI: 0.80-0.97, P = 0.010). CONCLUSIONS: DPP4 inhibition in CRC and lung cancer is associated with improved OS, which possibly may be due to the effect of DPP4 inhibition on immunoregulation of cancer.


Subject(s)
Colorectal Neoplasms/complications , Colorectal Neoplasms/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors , Lung Neoplasms/complications , Lung Neoplasms/epidemiology , Aged , Aged, 80 and over , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Molecular Targeted Therapy , Prognosis , Proportional Hazards Models , Public Health Surveillance , SEER Program , Treatment Outcome
18.
Mol Clin Oncol ; 10(1): 118-124, 2019 01.
Article in English | MEDLINE | ID: mdl-30655986

ABSTRACT

Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.

19.
Oxf Med Case Reports ; 2018(1): omx078, 2018 01.
Article in English | MEDLINE | ID: mdl-29340160

ABSTRACT

Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission. Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.

20.
MedEdPORTAL ; 14: 10746, 2018 08 30.
Article in English | MEDLINE | ID: mdl-30800946

ABSTRACT

Introduction: Physicians recognize the importance of clinical documentation for accuracy of coding and billing, but it is emphasized little in residency curricula, with an even smaller emphasis on oncology-specific documentation. We developed an educational curriculum to teach residents about clinical documentation for cancer patients. Our tool kit includes didactics, simulated history and physical (H&P) documentation, and personal feedback. Methods: A preintervention survey was first administered to gauge baseline knowledge. A simulated H&P was developed that required participants to complete their own assessment and plan. We delivered a 25-minute lecture regarding billing and coding along with documentation tips and tricks specific to hematology/oncology. Thereafter, we handed out a second H&P, and participants had to once again complete their own assessment and plan. These H&Ps were graded by three reviewers using a rubric. We then gave residents personalized feedback using the above data and administered a postintervention survey. Results: The postintervention survey revealed that 100% of the residents surveyed found this activity helpful, 83% noted that further knowledge of diagnosis codes was helpful to their learning, 100% noted that that this activity taught them to improve documentation, 91% said they were more likely to use cancer-specific diagnoses, and 91% said they would benefit from direct feedback-based education. Discussion: Didactic and formal education is more effective when combined with hands-on examples and direct personalized feedback.


Subject(s)
Curriculum/trends , Medical Oncology/education , Documentation/methods , Documentation/standards , Education, Medical/methods , Florida , Humans , Internal Medicine/education , Internship and Residency/methods , Medical History Taking/methods , Medical History Taking/standards , Quality Improvement , Surveys and Questionnaires
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