Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab.

Hyperprogressive disease in non-small cell lung cancer treated with immune checkpoint inhibitor therapy, fact or myth?

The therapeutic landscape for patients with non-small cell lung cancer (NSCLC) has dramatically evolved with the development and adoption of immune checkpoint inhibitors (ICI) as front-line therapy. These novel antibodies target the interactions in immunoregulatory pathways, between programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) and B7, resulting in the activation of T cells and cytotoxic response to induce an immunologic response. ICIs have demonstrated significant survival benefits and sustained responses in the treatment of NSCLC leading to the long-term survival of up to 5 year.

Treatment of Advanced-Stage Large Cell Neuroendocrine Cancer (LCNEC) of the Lung: A Tale of Two Diseases.

LCNEC of the lung comprises a small proportion of pulmonary malignancies. Traditionally, they have been classified based on histologic and immunohistochemistry characteristics with features of small cell and non-small cell lung cancer. The treatment outcome of advanced-stage LCNEC of the lung is poor with response rates ranging from 34 to 46% with platinum doublets, median progression-free survival (mPFS) ranging between 4.

Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines.

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood.

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers.

Recent application of immunotherapy in clinical oncology revolutionized our management of advanced human cancers. Check point inhibitors targeting CTLA4 and PD-1/PD-L1 axis are immunotherapeutic agents currently available to treat a variety of cancers. However, a novel therapeutic approach is needed to further improve patient outcome with these agents.

The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.

Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.

Systematic analysis of design and stratification for phase III trials in first-line advanced non-small cell lung cancer.

Background: A recent study reviewed phase III trials of first-line advanced non-small cell lung cancer (NSCLC) conducted from 1981 to 2010, and provided trends in the study outcome. However, such trials have never been analyzed in detail for design and stratification factors.

Methods: Phase III studies of systemic treatment for first-line advanced or metastatic NSCLC published in English literature between 1981 and 2010 were identified.

Impact Study: MK-0646 (Dalotuzumab), Insulin Growth Factor 1 Receptor Antibody Combined with Pemetrexed and Cisplatin in Stage IV Metastatic Non-squamous Lung Cancer.

Background: Insulin-like growth factor 1 receptor (IGF-1R) regulates cell growth, proliferation, and apoptosis. Adenocarcinoma and never-smokers have a higher expression of IGF-1R, which is associated with worse overall survival. Dalotuzumab-MK0646 (D) is a humanized monoclonal antibody that targets IGF-1R.

Infrequent chemoradiation-induced acute esophagitis in the Asian population: A meta-analysis of published clinical trials for unresectable stage III non-small cell lung cancer.

Severe (grade 3 or higher) esophagitis is one of the major toxicities for chemoradiation in the treatment of stage III non-small cell lung cancer (NSCLC). The difference among ethnic groups has never been investigated in detail. Prospective trials with concurrent platinum-containing chemoradiation in unresectable disease were investigated, and a total of 116 treatment arms with 7520 patients were identified.

A multicenter pilot study examining the role of circulating tumor cells as a blood-based tumor marker in patients with extensive small-cell lung cancer.

Background: Small-cell lung cancer (SCLC), a variant of lung cancer marked by early metastases, accounts for 13% of all lung cancers diagnosed in US. Despite high response rates to treatment, it is an aggressive disease with a median survival of 9-11 months for patients with extensive stage (EX-SCLC). Detection of circulating tumor cells (CTCs) is a novel laboratory technique currently in use to determine response to therapy and to predict prognosis in breast, colorectal, and prostate cancer.

Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.

Purpose: Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease.

Patients And Methods: Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.

Predictive factors in patients with advanced and metastatic squamous cell carcinoma of the head and neck: a study based on SWOG protocol S0420.

To evaluate the prognostic values of different protein expression in the progression of squamous cell carcinoma of the head and neck (SCCHN) patients, we conducted immunohistochemical (IHC) analysis in tissue samples of different patients enrolled on SWOG protocol S0420. S0420 was a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent SCCHN. The primary end point was response probability, i.

The Evolving Role of Maintenance Therapy Using Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in the Management of Advanced Non-Small-Cell Lung Cancer.

The epidermal growth factor receptor (EGFR) plays an important role in the development of many cancers, including non-small cell lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a class of novel biologically-targeted agents widely used in the management of recurrent non-small cell lung cancer. Erlotinib, one of the EGFR TKIs, is currently FDA approved in second and third line therapy.

Lung cancer management in 2010.

The introduction of newer therapies and approaches for management has led to a renewed excitement in the field of lung cancer. This trend has continued in 2010 with the adoption of the new staging system recommended by the International Association for the Study of Lung Cancer (IASLC). Novel targets, such as EML4-ALK, have been identified and agents targeting these abnormalities have shown promise in uncontrolled clinical trials, while other strategies, including combining targeted agents with cytotoxic chemotherapy in unselected patients, have not proven to be successful.

Potential role of platelet-derived growth factor receptor inhibition using imatinib in combination with docetaxel in the treatment of recurrent non-small cell lung cancer.

Introduction: Platelet-derived growth factor receptor (PDGFR) is expressed in lung cancer and is involved in angiogenesis. Preclinical models demonstrated that imatinib (Im) regulates angiogenesis through PDGFR inhibition and enhances efficacy of chemotherapy.

Hypothesis: We hypothesized that Im plus docetaxel (D) would have a synergistic effect detectable by an increase in response rate in patients with recurrent non-small cell lung cancer (NSCLC).

Phase II evaluation of sorafenib in advanced and metastatic squamous cell carcinoma of the head and neck: Southwest Oncology Group Study S0420.

Purpose: We conducted a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The primary end point was response probability (ie, confirmed complete and partial response [PR]).

Patients And Methods: Chemotherapy-naïve patients with metastatic, persistent, or recurrent SCCHN who received one induction or fewer or received an adjuvant chemotherapy regimen, who had adequate organ function, and who had a performance status View Article and Find Full Text PDF

Randomized phase II trial of cisplatin, etoposide, and radiation followed by gemcitabine alone or by combined gemcitabine and docetaxel in stage III A/B unresectable non-small cell lung cancer.

Purpose: Southwest Oncology Group 9504 demonstrated the feasibility and potential benefit of docetaxel consolidation after etoposide, cisplatin, and radiotherapy in patients with locally advanced non-small cell lung cancer. Our study assessed consolidation with either gemcitabine alone or with docetaxel after identical chemoradiation as used in Southwest Oncology Group 9504.

Methods: Patients with stage III non-small cell lung cancer and good performance status were included.

Promising survival in patients with recurrent non-small cell lung cancer treated with docetaxel and gemcitabine in combination as second-line therapy.

Introduction: Lung cancer is the leading cause of cancer death in men and women, and current second-line chemotherapy regimens yield relatively poor response and survival rates.

Hypothesis: We hypothesized that the combination of weekly docetaxel (D) and gemcitabine (G) would show activity in the second-line setting. We therefore conducted a phase II trial evaluating this regimen in patients with relapsed or progressive non-small cell lung cancer (NSCLC) after first-line platinum-based therapy.

Dysgenetic hypoplastic kidney simulating metastatic lung carcinoma.

We describe a 57-year-old male with prior history of an absent right kidney and kidney transplant who was found to have lung cancer. Integrated positron emission tomography (PET) and computerized tomography (CT) scan was done for staging and showed uptake in the right upper lung primary and right renal fossae region which was suggestive of metastatic disease. An excisional biopsy of the right renal fossae mass showed that it was a hypoplastic kidney simulating a metastatic focus on PET scan.

Phase I study of liposome-encapsulated c-raf antisense oligodeoxyribonucleotide infusion in combination with radiation therapy in patients with advanced malignancies.

Purpose: Raf proteins are key elements of growth-related cellular signaling pathways and are a component of cancer cell resistance to radiation therapy. Antisense oligonucleotides to c-raf-1 permit highly selective inhibition of the gene product and offer a strategy for sensitizing cancer cells to radiation therapy. In this dose escalation study, we evaluated the safety of combined liposomal formulation of raf antisense oligonucleotide (LErafAON) and radiation therapy in patients with advanced malignancies.

Delivery of a liposomal c-raf-1 antisense oligonucleotide by weekly bolus dosing in patients with advanced solid tumors: a phase I study.

Purpose: Rapid cleavage in vivo and inefficient cellular uptake limit the clinical utility of antisense oligonucleotides (AON). Liposomal formulation may promote better intratumoral AON delivery and inhibit degradation in vivo. We conducted the first clinical evaluation of this concept using a liposomal AON complementary to the c-raf-1 proto-oncogene (LErafAON).

Topotecan in the treatment of relapsed small cell lung cancer patients with poor performance status.

Topotecan is the only single-agent therapy approved by the U.S. Food and Drug Administration for the treatment of patients with recurrent small cell lung cancer (SCLC).