Investigating Nonadherence in an Integrated Diabetic Limb Salvage Programme: Reasons, Associated Factors, and Impacts on Care Outcomes.

Adherence to treatment plans is crucial for patients with diabetic foot ulcers (DFUs) to achieve positive outcomes. With limited understanding of nonadherence and its impacts on care outcomes, this study aimed to explore the reasons and factors associated with nonadherence in an integrated diabetic limb salvage (DLS) programme and evaluate its effects on care outcomes. This study included 2798 DFU patients who were enrolled in an integrated DLS programme across multiple institutions in central and northern Singapore from 2020 to 2021.

Rapid Access From Primary Care to a Multidisciplinary Clinic at Tertiary Care Improves Clinical Outcomes for Patients With Diabetic Foot Ulcers: Results From Diabetic Foot in Primary and Tertiary (DEFINITE) Care's Lower Extremity Amputation Prevention Program (LEAPP) Clinic.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional, multidisciplinary team (MDT) program for patients with diabetic foot ulcers (DFU) within a healthcare cluster in Singapore. This is one of our subgroup analyses within DEFINITE Care, assessing clinical outcomes of lower extremity amputation prevention program (LEAPP), a multidisciplinary diabetic foot clinic, and non-LEAPP patients within the program. From June 2020 to June 2022, 2798 patients within the DEFINITE cohort completed a minimum of 12-month follow up.

A phase I trial of the pan-ERBB inhibitor neratinib combined with the MEK inhibitor trametinib in patients with advanced cancer with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation or KRAS mutation.

Purpose: Aberrant alterations of ERBB receptor tyrosine kinases lead to tumorigenesis. Single agent therapy targeting EGFR or HER2 has shown clinical successes, but drug resistance often develops due to aberrant or compensatory mechanisms. Herein, we sought to determine the feasibility and safety of neratinib and trametinib in patients with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation and KRAS mutation.

A Phase I Dose-Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies.

Purpose: As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically "cold" cancers, which are intrinsically insensitive to immunotherapy, as well as in "hot/warm" metastatic cancers that are, atypical of such cancers, resistant to immunotherapy.

Patients And Methods: In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400-640 mg/m) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1-2, while the latter was administered on day 8 of cycles 1-4.

Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers.

Background: We performed a phase I modified 3 + 3 dose escalation study to evaluate the safety and activity of bevacizumab plus gemcitabine and nab-paclitaxel in patients with advanced solid tumours.

Methods: Patients were given fixed dose gemcitabine plus increasing doses of nab-paclitaxel and bevacizumab. Toxicity, response, and association with VEGF polymorphism was analysed.

Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib (as a c-SRC inhibitor) in patients with advanced cancer.

Background Both MET and c-SRC are important mediators of cancer progression and there is cross talk between the two molecules. Preclinical studies have demonstrated combination of MET and c-SRC inhibitors is effective in multiple cancer types. Methods We analyzed the safety and efficacy of administering a c-SRC inhibitor (dasatinib) in combination with a MET inhibitor (crizotinib) in a two-arm concurrent phase I study.

Phase I clinical trial of combination imatinib and ipilimumab in patients with advanced malignancies.

Background: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer.

Phase I combination of pazopanib and everolimus in PIK3CA mutation positive/PTEN loss patients with advanced solid tumors refractory to standard therapy.

Purpose: Combining agents that block both the VEGF and PI3K/AKT/mTOR pathways may be synergistic. We explored a novel dosing schedule to assess safety, toxicity and activity in patients with advanced solid tumors.

Patients And Methods: Patients with refractory solid tumors were enrolled in a modified 3 + 3 Phase I dose escalation study to determine dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of a combination of everolimus (mTOR inhibitor) and pazopanib (tyrosine kinase inhibitor with anti-VEGF activity).

Hepatic arterial infusion therapy in advanced cancer and liver-predominant disease: the MD Anderson Experience.

Background/aims: Liver metastases in patients with cancer are associated with a poor prognosis. We assessed the clinical outcomes in patients with advanced cancer and predominant liver involvement treated on hepatic arterial infusion (HAI chemotherapy protocols.

Methodology: We retrospectively analyzed the outcomes of patients referred to the Phase I Clinical Trials Program between April 2004 and September 2009.

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.

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).

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy.

Background: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population.

Methods: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.

Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy.

Background: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v.

Intravenous corticosteroids to reduce gemtuzumab ozogamicin infusion reactions.

Objective: To assess whether the addition of a brief course of intravenous corticosteroids reduces the incidence of infusion-related adverse events associated with gemtuzumab ozogamicin (GO) administration.

Methods: One hundred forty-three sequential patients received GO-based therapy for refractory myeloid leukemias: 110 patients received the standard regimen of acetaminophen 650 mg orally with diphenhydramine 50 mg intravenously and 33 patients received the same premedications with methylprednisolone sodium succinate 50 mg intravenous piggyback (IVPB) prior to infusion and repeated 1 hour into the infusion.

Results: Of 110 patients who received GO with standard premedications alone, 32 (29%) had grade 2 or above infusion-related adverse events.