Immune checkpoint inhibitors (ICIs) have become an important means of cancer treatment, and their application in the clinic is becoming more and more widespread. The adverse reactions caused by ICIs are gradually recognized. Among them, immunotherapy-related diabetes is a rare adverse reaction and type 1 diabetes mellitusis common. With the wide application of ICIs combined with chemotherapy in lung cancer patients, patients with type 2 diabetes mellitus have gradually been discovered during the treatment. However, the effect of continued use of ICIs maintenance therapy on blood glucose and ICIs treatment process in these patients is still unclear. This article reports two cases of type 2 diabetes mellitus induced by immune checkpoint inhibitor combined with chemotherapy, one of whom converted to type 1 diabetes mellitus, in order to increase the understanding of immunotherapy-related diabetes.
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Diabetes Mellitus, Type 2/drug therapy* ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy/adverse effects* ; Lung Neoplasms/therapy* ; Molecular Targeted Therapy

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit.We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.
Antineoplastic Agents ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Humans ; Medication Therapy Management ; Molecular Targeted Therapy ; adverse effects ; methods ; Neoplasms ; drug therapy ; genetics ; Pharmacogenomic Testing ; Therapies, Investigational ; methods

Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.
Drug-Related Side Effects and Adverse Reactions ; Humans ; Molecular Targeted Therapy* ; Receptor, Epidermal Growth Factor ; Response Evaluation Criteria in Solid Tumors ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A

Numerous disorders and etiologies may underlie increased eosinophil counts. Hypereosinophilia (HE) is defined as a peripheral blood eosinophil count greater than 1,500/mm3 and may be potentially harmful because of tissue damage. Hypereosinophilic syndrome (HES) also represents a heterogeneous disorder characterized by persistent HE with the evidence of organ dysfunction, clinical symptoms, or both caused by eosinophilia. The refining criteria and subclassification of HE and HES are currently being revised on cellular and molecular based diagnostic methods. Initial approaches focus on evaluating various underlying causes, including helminthic infections, adverse drug reactions, allergic diseases, and neoplastic diseases. When secondary causes of HE are excluded, the workup should proceed to the evaluation of primary/clonal bone marrow disease, including fip 1-like 1-platelet driven growth factor receptor alpha (FIP1L1-PDGFRA) mutation. Concurrently, if the patient has symptoms and signs, organ damage or dysfunction must be evaluated. Although, corticosteroids are the mainstay of therapy in confirmed HES, imatinib is considered a definitive treatment for FIP1L1-PDGFRA, platelet driven growth factor receptor beta rearranged HE and HES. In this article, we discuss recent advances in the classification of and practical approaches to HE and HES. In addition, we introduce several promising therapies for HE and HES.
Adrenal Cortex Hormones ; Blood Platelets ; Bone Marrow Diseases ; Classification* ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Eosinophils ; Helminths ; Humans ; Hypereosinophilic Syndrome ; Molecular Targeted Therapy ; Imatinib Mesylate

OBJECTIVETo investigate the prevalence and treatment of oral mucositis caused by concurrent chemoradiotherapy and/or molecular targeted therapy in the patients with advanced squamous cell carcinoma of the head and neck.

METHODSA retrospective study of the incidence and treatment of oral mucositis was performed in 179 patients (155 male and 24 female;124 patients at stage III and 55 patients at stage IV) receiving concurrent chemotherapy and (or) molecular targeted therapy between November 2007 and November 2010. Grade I, II, III and IV oral mucositis occurred respectively in 49, 50, 67 and 13 patients. All the patients received oral mucositis prophylaxis. After the occurrence of oral mucositis, conventional treatment of mucositis combined with quinolone antibiotics were applied.

RESULTSOf the patients, 99 patients with grade I or II and 4 patients with grade III oral mucositis were effectively managed by conventional treatment; 76 patients with grade III or IV oral mucositis were also significantly controled by conventional treatment plus antibiotics. After the treatments, all patients with oral mucositis were under control, with the decrease in the grade of oral mucositis, the reduction of oral pain and the improvement in ability to eat. None of them had radiation treatment breaks.

CONCLUSIONSCombined modality therapy can effectively control chemoradiation-induced oral mucositis in patients with head and neck squamous cell carcinoma, grade I and II oral mucositis were cured by conventional treatment and quinolone antibiotics play a key role in the treatments for grade III and IV oral mucositis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; radiotherapy ; Chemoradiotherapy ; adverse effects ; Combined Modality Therapy ; Female ; Head and Neck Neoplasms ; drug therapy ; radiotherapy ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy ; adverse effects ; Retrospective Studies ; Stomatitis ; drug therapy ; etiology ; Young Adult

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.
Antineoplastic Agents, Hormonal/adverse effects ; Disease Management ; Disease Progression ; Endometrial Hyperplasia/classification/etiology/*therapy ; Female ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Hysterectomy ; Molecular Targeted Therapy/methods ; Progesterone Congeners/therapeutic use ; Risk Factors ; Tamoxifen/adverse effects

BACKGROUND: The present study describes our 10-year experience with uveoretinal adverse events that manifest because of chemotherapy. METHODS: A retrospective chart review was performed for all patients who presented to the ophthalmologic department while undergoing systemic chemotherapy between July 2005 and June 2015. RESULTS: A total of 55 patients (mean age, 51.2 years, 38 women [69.1%]) suspected of having uveoretinal disease owing to the use of chemotherapeutic agents alone were enrolled. Breast cancer was the predominant disease (36.4%); noninfectious anterior uveitis (21.8%) was the most common condition. Bilateral involvement was observed in 16 patients (29.1%). Although cisplatin (21.8%) was the most commonly used drug, daunorubicin, cytarabine, tamoxifen, toremifene, and imatinib were also frequently used. The median duration until ophthalmologic diagnosis was 208.5 days (range, 19–5,945 days). The proportion of patients with final visual acuity (VA) < 20/40 Snellen VA (0.5 decimal VA) was 32.7%. However, no relationship was observed between final VA < 20/40 and age, sex, therapeutic agents, and metastasis. CONCLUSION: Uveoretinal complications were mostly mild to moderate and exhibited a favorable response to conservative therapy. A considerable number of patients exhibited significant irreversible loss of vision after cessation of the causative chemotherapeutic agent. Ophthalmological monitoring is required during chemotherapy.
Antineoplastic Agents ; Breast Neoplasms ; Cisplatin ; Cytarabine ; Daunorubicin ; Diagnosis ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Imatinib Mesylate ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Retrospective Studies ; Tamoxifen ; Toremifene ; Uveitis ; Uveitis, Anterior ; Visual Acuity

adverse events (AEs) were reviewed and evaluated.RESULTS: All patients had complete follow-up records, and the median follow-up time was 14.5 months (5.5–20.5 months). Among the 48 patients, 14.58% achieved a partial response and 52.08% achieved stable disease. The overall response rate and disease control rate were 14.58% and 66.67%, respectively. The median time that the 48 patients received oral apatinib was 8.2 months. The median PFS was 4.6 months (95% confidence interval [CI]=3.31–5.26) and OS was 13.9 months (95% CI=8.37–17.96). The main apatinib-related adverse reactions were leukopenia (37.5%), neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1–2, and no drug-related death occurred.CONCLUSIONS: Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.]]>
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Fatigue ; Follow-Up Studies ; Hand-Foot Syndrome ; Hemorrhage ; Humans ; Hypertension ; Leukopenia ; Molecular Targeted Therapy ; Neutropenia ; Proteinuria ; Radiotherapy ; Retrospective Studies ; Uterine Cervical Neoplasms

OBJECTIVE: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. MATERIALS AND METHODS: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. RESULTS: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. CONCLUSION: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*adverse effects/therapeutic use ; Ascites/pathology/radiography ; Benzamides/*adverse effects/therapeutic use ; Echocardiography/methods ; Edema/pathology/radiography ; Female ; Gastrointestinal Stromal Tumors/drug therapy/pathology/*radiography ; Gastrointestinal Tract/pathology/*radiography ; Heart Failure/radiography ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/*adverse effects ; Pericardial Effusion/pathology/radiography ; Peritoneal Neoplasms/diagnosis/radiography/secondary ; Piperazines/*adverse effects/therapeutic use ; Pleural Effusion/pathology/radiography ; Pyrimidines/*adverse effects/therapeutic use ; Radiology ; Retrospective Studies ; Tomography, X-Ray Computed

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Child ; Dasatinib ; Female ; Humans ; Male ; Molecular Targeted Therapy ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Protein Kinase Inhibitors ; administration & dosage ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; administration & dosage ; adverse effects ; Thiazoles ; administration & dosage ; adverse effects