No abstract

As the economic burden and nancial distress (FD) resulting from cancer care are increasingly recognized, FD remains inadequately understood from the perspective of patients and their spousal caregiver, the relational context where most nancial and treatment decisions are navigated. Therefore, we assessed FD in both patients with advanced cancer and their spouses to identify symptom and QOL correlates. We additionally examined if illness communication moderated the association between FD and QOL. MethodsPatients undergoing treatment for stage III/IV lung cancer or grade III/IV primary brain tumor and their spouses completed measures of their own FD, QOL, symptoms, perception of their spouse's symptoms, and overall illness communication. ResultsPatients (62.7%) and spouses (64.7%) endorsed FD; however, spouses rated FD with greater relative severity. For both, FD was associated with greater anxiety, depression, and poorer physical QOL. For patients, FD was additionally associated with poorer mental QOL. Spousal caregivers accurately perceived patient FD, yet patients underreported spouse's FD by a clinically meaningful difference. A 3way interaction (FD X role X illness communication) revealed (b = .40, p = .041) that illness communication moderated the association between FD and physical QOL for spouses only. ConclusionIn the advanced cancer setting, FD is prevalent in both patients and their caregivers and associated with psychological distress and poor physical QOL. Results suggest that optimal FD interventions should include patients and spouses. As illness communication appears to buffer the negative association of FD with physical QOL, studies targeting illness communication de cits in couples facing advanced disease are warranted.

Despite the high radiographic response rate in recurrent glioblastoma to antiangiogenic therapy, the impact of these agents on improving overall survival have been disappointing. A lack of survival benefit has resulted in an increased effort to better understand the mechanisms underlying resistance to antiangiogenic therapy. Adaptive (evasive) resistance and intrinsic (pre-existing) nonresponsiveness have emerged as modes of resistance to antiangiogenic therapy with multiple mechanisms believed to contribute to each type. This increasing knowledge regarding these mechanisms of resistance has led to an increased focus on the tumor microenvironment in aiding in the determination of the optimal biologic dose of antiangiogenic therapy. Although there is a lack of durable responses to current antiangiogenic treatments, there is an important role for angiogenesis inhibitors in the treatment of high-grade gliomas. Current efforts are underway regarding optimizing antiangiogenic therapy as an adjunctive treatment to radiation and chemotherapy.

Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. Results: In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T1/2 was 2–3 h with a dose dependent increase in the Cmax. Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. Conclusion: Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.

Glioblastoma is the most deadly primary brain tumor in adults and has long represented a therapeutic challenge. Disease recurrence is inevitable, and the management of recurrent disease is complicated by spontaneous or induced tumor heterogeneity which confers resistance to therapy and increased oncogenicity. EGFR and the tumor-specific mutation EGFRvIII is commonly altered in glioblastoma making it an appealing therapeutic target. Immunotherapy is an emerging and promising therapeutic approach to glioma and the EGFRvIII vaccine, rindopepimut, is the first immunotherapeutic drug to enter Phase III clinical trials for glioblastoma. Rindopepimut activates a specific immune response against tumor cells harboring the EGFRvIII protein. This review evaluates the recently completed ReACT Phase II trial using rindopepimut plus bevacizumab in the setting of EGFRvIII-positive recurrent glioblastoma (Clinical Trials identifier: NCT01498328).