Regorafenib plus nivolumab in patients with mismatch repair-proficient/microsatellite stable metastatic colorectal cancer: a single-arm, open-label, multicentre phase 2 study.

Background: Anti-programmed cell death protein 1 antibodies plus multikinase inhibitors have shown encouraging activity in several tumour types, including colorectal cancer. This study assessed regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.

Methods: This single-arm, open-label, multicentre phase 2 study enrolled adults from 13 sites in the USA with previously treated advanced microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.

Eribulin Plus Pembrolizumab in Patients with Metastatic Triple-Negative Breast Cancer (ENHANCE 1): A Phase Ib/II Study.

Purpose: As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings.

Patients And Methods: In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting.

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours.

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]).

Patients And Methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry.

Eribulin versus dacarbazine in patients with leiomyosarcoma: subgroup analysis from a phase 3, open-label, randomised study.

Background: This subgroup analysis of a phase 3 study compares outcomes for eribulin versus dacarbazine in patients with leiomyosarcoma.

Methods: Patients ≥18 years old with advanced liposarcoma or leiomyosarcoma, ECOG PS ≤2, and ≥2 prior treatment regimens were randomly assigned (1:1) to eribulin mesylate (1.4 mg/m² intravenously on day 1 and day 8) or dacarbazine (either 850, 1000, or 1200 mg/m² intravenously) every 21 days until disease progression.

A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors.

Background: Sorafenib and dacarbazine have low single-agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes.

Materials And Methods: Patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m intravenously (later reduced to 850 mg/m).

A phase 1 study of eribulin mesylate (E7389), a novel microtubule-targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314).

Background: Eribulin mesylate is a novel anticancer agent that inhibits microtubule growth, without effects on shortening, and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose-limiting toxicities (DLTs), maximum tolerated or recommended phase 2 dose (MTD/RP2D), and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid (excluding central nervous system) tumors.

Methods: Eribulin was administered intravenously on days 1 and 8 in 21-day cycles.

Treatment-refractory ALK-positive inflammatory myofibroblastic tumour of the oral cavity.

We present a challenging case of a previously healthy 23-year-old man who developed an inflammatory myofibroblastic tumour of the hard palate, harbouring a rearrangement of the anaplastic lymphoma kinase (ALK) locus. Despite surgical intervention, radiotherapy and ALK-inhibition therapy, the tumour recurred locally and metastasised to regional lymph nodes, and the patient passed away roughly 9 months after diagnosis from local progression. The rapid progression of this patient's disease and its resistance to treatment demonstrate the potentially aggressive clinical course of inflammatory myofibroblastic tumours.

Comorbid insomnia and sleep apnea in Veterans with post-traumatic stress disorder.

Purpose: The purpose of this study was to determine the impact of insomnia in Veterans with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) on health-related outcomes before and after 12 weeks of continuous positive airway pressure (CPAP) treatment.

Methods: We conducted a prospective cohort study of Veterans with PTSD and documented apnea hypopnea index (AHI) ≥ 5 with and without clinically significant insomnia as determined by the Insomnia Severity Index (ISI). Health-related outcomes including PTSD checklist (PCL-M), SF-36, and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline and 12 weeks after initiation of OSA treatment.

A Randomized Crossover Trial Evaluating Continuous Positive Airway Pressure Versus Mandibular Advancement Device on Health Outcomes in Veterans With Posttraumatic Stress Disorder.

Study Objectives: Despite the overall improvement in posttraumatic stress disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP) therapy, adherence to CPAP is far worse in veterans with PTSD compared to the general population with obstructive sleep apnea (OSA). The aim of this study was to compare the efficacy, adherence, and preference of CPAP versus mandibular advancement device (MAD) and the effect of these treatments on health outcomes in veterans with PTSD.

Methods: Forty-two subjects with PTSD and newly diagnosed OSA by polysomnography were treated in a randomized, crossover trial of 12 weeks with CPAP alternating with MAD separated by a 2-week washout period.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine.

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included.

Evaluation of Quality of Life at Progression in Patients with Soft Tissue Sarcoma.

. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal tissue, with international incidence estimates between 1.8 and 5 per 100,000 per year.

Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial.

Background: A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control).

Methods: We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries.

Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma.

Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo.

Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy.

Background: Preclinical studies have documented antitumor activity of PARP inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study aimed to translate that observation into a clinical trial to assess the efficacy and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing sarcoma (EWS) progressing after prior chemotherapy.

Methods: In this nonrandomized phase II trial, adult participants with radiographically measureable metastatic EWS received olaparib tablets, 400 mg orally twice daily, until disease progression or drug intolerance.

Treatment of opioid-related central sleep apnea with positive airway pressure: a systematic review.

Objective: To systematically review the various modalities of positive airway pressure (PAP) in the treatment of opioid-related central sleep apnea (CSA).

Design: Systematic review.

Interventions: MEDLINE, the Cochrane Library, and EMBASE were screened through March 2013 to identify articles which investigated treatment of opioid related CSA with PAP.

A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma.

Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma.

The cyclin-dependent kinase inhibitor flavopiridol potentiates doxorubicin efficacy in advanced sarcomas: preclinical investigations and results of a phase I dose-escalation clinical trial.

Purpose: Dysregulated cyclin-dependent kinases are important to the growth of some sarcomas. Flavopiridol is a pan-CDK inhibitor that has been shown to potentiate chemotherapy. As such, we explored the potentiation of doxorubicin by flavopiridol in sarcoma, in vitro and in vivo, and conducted a phase I trial of flavopiridol with doxorubicin in patients with advanced sarcomas.

Appraising the current role of chemotherapy for the treatment of sarcoma.

Sarcomas are a heterogeneous group of relatively rare mesenchymal neoplasms. They can be grouped into two general categories: soft tissue sarcoma (STS) and primary bone sarcoma, which are treated differently. Because sarcomas are relatively rare and complex with a wide variety of different histopathologic subtypes, evaluation by multidisciplinary teams who have expertise in the field is recommended.

Comparison of doxorubicin and weekly paclitaxel efficacy in metastatic angiosarcomas.

Background: Data regarding the role of anthracyclines and taxanes as first-line treatments of metastatic angiosarcoma are limited.

Methods: Records of 117 metastatic angiosarcoma patients who were treated with either doxorubicin or weekly paclitaxel were reviewed.

Results: Seventy-five patients (64%) were treated with weekly paclitaxel and 42 (36%) with single-agent doxorubicin.

An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions.

Background: BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported.

Methods: Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center.

Activity of Sorafenib against desmoid tumor/deep fibromatosis.

Background: Desmoid tumors (deep fibromatoses) are clonal connective tissue malignancies that do not metastasize, but have a significant risk of local recurrence, and are associated with morbidity and occasionally mortality. Responses of desmoid patients to sorafenib on an expanded access program led us to review our experience.

Methods: After Institutional Review Board (IRB) approval, we reviewed data for 26 patients with desmoid tumors treated with sorafenib.

Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.

Chemotherapy in clear cell sarcoma.

Clear cell sarcoma is a rare translocation-related sarcoma. There have been few studies documenting the response rate and progression-free survival in clear cell sarcoma patients treated with palliative chemotherapy. The prospectively maintained databases of two referral centres were searched to identify clear cell sarcoma patients treated with chemotherapy.