Immunogenicity of Inactivated Varicella Zoster Vaccine in Autologous Hematopoietic Stem Cell Transplant Recipients and Patients With Solid or Hematologic Cancer.

Background: In phase 3 trials, inactivated varicella zoster virus (VZV) vaccine (ZV) was well tolerated and efficacious against herpes zoster (HZ) in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and patients with solid tumor malignancies receiving chemotherapy (STMc) but did not reduce HZ incidence in patients with hematologic malignancies (HMs). Here, we describe ZV immunogenicity from these studies.

Methods: Patients were randomized to ZV or placebo (4 doses).

Safety and efficacy of inactivated varicella zoster virus vaccine in immunocompromised patients with malignancies: a two-arm, randomised, double-blind, phase 3 trial.

Background: Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies.

Methods: This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries.

First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors.

Background C-Met, which is frequently activated in multiple cancers, has been implicated in tumor formation, progression, metastasis, angiogenesis, and resistance to multiple therapies. MK-8033 is a small-molecule inhibitor of c-Met that binds preferentially to the activated conformation, and has demonstrated anti-tumor activity in preclinical models. This first-in-human trial was performed to establish the safety and maximum tolerated dose (MTD), as well as preliminary pharmacokinetics (PK) and clinical activity.

A Randomized, Open-Label, Safety and Exploratory Efficacy Study of Kanglaite Injection (KLTi) plus Gemcitabine versus Gemcitabine in Patients with Advanced Pancreatic Cancer.

This study was designed to assess the safety and preliminary efficacy of KLTi plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer. In a randomized, open-label study, patients with locally advanced or metastatic pancreatic cancer were randomized 2:1 to receive KLTi plus gemcitabine or gemcitabine monotherapy. Three sequential cohorts were tested at 30 g/day, 50 g/day, and 30 g/day.

Current Status of Biosimilars in Oncology.

Four medicinal cancer biological blockbusters will end their patent lifespan by 2020. It is estimated that the total market for cancer biologicals will reach approximately US$68 billion at that time. Approximately 20 biosimilars have entered the European market since the launch of the original approval guidelines in 2005, and four biosimilars have been approved in the USA since 2015.

Electrocardiographic Characterization of Ramucirumab on the Corrected QT Interval in a Phase II Study of Patients With Advanced Solid Tumors.

Lessons Learned: Cardiotoxicity can be a serious complication of anticancer therapies. To enable earlier identification of drug-related cardiac effects, the International Conference on Harmonization (ICH) adopted the ICH E14 Guidelines for evaluating the potential for QT/corrected QT (QTc) interval prolongation and proarrhythmic potential for nonantiarrhythmic drugs.The results of the evaluation of ramucirumab on the QT/QTc interval show a lack of effect on QTc prolongation in patients with advanced cancer.

Phase 1 Study of Monotherapy with KHK2866, an Anti-Heparin-Binding Epidermal Growth Factor-Like Growth Factor Monoclonal Antibody, in Patients with Advanced Cancer.

Background: KHK2866 is a recombinant, humanized, non-fucosylated, monoclonal antibody directed at heparin-binding epidermal growth factor-like growth factor (HB-EGF).

Objective: To determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, potential immunogenicity, and preliminary clinical efficacy of KHK2866 monotherapy in patients with advanced and refractory cancer in a first-in-human, phase 1 study.

Materials And Methods: Using a standard 3 + 3 dose-escalation design, 20 patients received KHK2866 (0.

Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab.

Purpose: One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago.

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations.

Melanoma remains a critical public health problem worldwide. Patients with stage IV disease have very poor prognosis and their 1-year survival rate is only 25%. Until recently, systemic treatments with a positive impact on overall survival (OS) had remained elusive.

Biosimilars 101: considerations for U.S. oncologists in clinical practice.

Biosimilars of biologics used for cancer treatment and supportive care are expected to enter the U.S. market soon.

Dual inhibition of the vascular endothelial growth factor pathway: a phase 1 trial evaluating bevacizumab and AZD2171 (cediranib) in patients with advanced solid tumors.

Background: The current study was conducted to evaluate the safety and biological activity of dual inhibition of the vascular endothelial growth factor (VEGF) pathway with combined bevacizumab and cediranib (a VEGF receptor tyrosine kinase inhibitor).

Methods: This was a 3 + 3 dose escalation study in patients with advanced solid tumors. Cediranib was given orally daily for 21 days and bevacizumab intravenously every 2 weeks.

Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) in immunocompromised adults.

Background: Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) were assessed in immunocompromised adults.

Methods: In a randomized, double-blind, placebo-controlled, multicenter study, 4 doses ZVHT or placebo were administered approximately 30 days apart to adults with either solid tumor malignancy (STM); hematologic malignancy (HM); human immunodeficiency virus (HIV) with CD4(+) ≤200; autologous hematopoietic stem-cell transplant (HCT) or allogeneic-HCT recipients. Varicella-zoster virus (VZV) T-cell responses by interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) and VZV antibody concentrations by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and approximately 28 days after each dose.

A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma.

Cilengitide (EMD 121974) is a selective inhibitor of integrins αvβ3 and αvβ5. The αvβ3 promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide.

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

Background: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models.

Methods: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.

Retrospective analysis of satraplatin in patients with metastatic urothelial cancer refractory to standard platinum-based chemotherapy.

Unlabelled: Satraplatin is a novel platinum agent with favorable clinical attributes including oral bioavailability and lack of significant treatment-associated neuropathy and nephropathy. Furthermore, preclinical studies have shown that satraplatin is active is cisplatin-resistant tumors. We retrospectively evaluated the activity of satraplatin in patients with cisplatin or carboplatin-refractory urothelial carcinoma and demonstrated lack of significant antitumor activity in this population.

Phase I Dose Escalation Study of Sodium Stibogluconate (SSG), a Protein Tyrosine Phosphatase Inhibitor, Combined with Interferon Alpha for Patients with Solid Tumors.

Purpose: Sodium stibogluconate (SSG), a small molecule inhibitor of protein tyrosine phosphatases, combined with IFN-alpha-2b (IFN-α) inhibited solid tumor cell line growth in vitro. We conducted a phase I clinical trial with SSG plus IFN-α in advanced cancer patients to assess tolerance, maximum tolerated dose (MTD) and immune system effects.

Experimental Design: SSG was administered intravenously alone for five days of week 1, cycle 1 (21 days per cycle) and together with IFN-α 2b s (3 million units sc TIW) in week 2, and after a rest during week 3, on a 2-week on/1-week off cycle.

Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases.

Purpose: This pilot clinical trial explored the feasibility, safety, and efficacy of regional hepatic therapy combined with systemic anticancer agents in patients with refractory solid tumors and extensive unresectable liver involvement, including those with compromised hepatic function.

Patients And Methods: Six patients with colorectal (N = 3), ovarian (N = 2), and hepatocellular carcinoma (N = 1) received intra-arterial hepatic oxaliplatin followed by intravenous 5-fluorouracil, leucovorin, and bevacizumab every 2 weeks until disease progression. All had extensive liver metastases; four had elevated baseline serum total bilirubin.

Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma.

Background: Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.

Methods: The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma.

A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver.

Background: Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases.

Methods: Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m(2) to 175 mg/m(2) and intra-arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m(2) intravenously (iv) and 5-fluorouracil 300 mg/m(2) bolus plus 600 mg/m(2) iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3).

Chemokine expression in tumor-to-tumor metastasis.

Chemokines play an important role in cancer metastasis by modulating the directional cell movement and migration of tumor cells. The most commonly overexpressed chemokine receptor in human cancer is CXCR4. Once activated by its ligand CXCL12 (stromal cell-derived factor-1 ligand/SDF1), CXCR4 stimulates several key migratory, proliferative and survival signaling cellular pathways.

The clinical efficacy of combination of docetaxel and temozolomide in previously treated patients with stage IV melanoma.

No standard therapy exists for patients with metastatic melanoma whose disease failed to respond to first-line systemic treatment. We conducted a retrospective study to evaluate the clinical efficacy of the combination of docetaxel and temozolomide in previously treated patients. We searched our institution's patient and pharmacy databases for patients with metastatic melanoma who received docetaxel-tamozolomide and reviewed their medical records.

A phase I clinical trial of darinaparsin in patients with refractory solid tumors.

Purpose: Darinaparsin, an organic arsenic, targets essential cell survival pathways. We determined the dose-limiting toxicity (DLT) and maximum tolerated dose of darinaparsin in patients with advanced cancer.

Experimental Design: Patients with solid malignancies refractory to conventional therapies were treated with i.

Phase I/II trial of tremelimumab in patients with metastatic melanoma.

Purpose: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development.

Patients And Methods: Twenty-eight patients with metastatic melanoma received monthly intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to determine recommended monthly phase II dose.

Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma.

Purpose: In a search for more effective combination chemotherapy for the treatment of metastatic melanoma, we conducted a phase I trial of a novel combination of docetaxel, temozolomide, and cisplatin.

Methods: Patients with inoperable or recurrent metastatic melanoma with a Zubrod performance status of 2 or less and adequate organ function were eligible. The dose of docetaxel was escalated between cohorts of patients, and the doses of temozolomide and cisplatin were fixed.