Phase Ib and Expansion Study of Gemcitabine, Nab-Paclitaxel, and Ficlatuzumab in Patients With Metastatic Pancreatic Cancer.

Background: In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of hepatocyte growth factor (HGF) signaling using ficlatuzumab, a recombinant humanized anti-HGF antibody, and gemcitabine reduced tumor burden.

Methods: Patients with previously untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3 + 3 design of 2 dose cohorts of ficlatuzumab 10 and 20 mg/kg administered intravenously every other week with gemcitabine 1000 mg/m2 and albumin-bound paclitaxel 125 mg/m2 given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose of the combination.

Developmental impacts of the COVID-19 pandemic on young children: a conceptual model for research with integrated administrative data systems.

The COVID-19 pandemic made its mark on the entire world, upending economies, shifting work and education, and exposing deeply rooted inequities. A particularly vulnerable, yet less studied population includes our youngest children, ages zero to five, whose proximal and distal contexts have been exponentially affected with unknown impacts on health, education, and social-emotional well-being. Integrated administrative data systems could be important tools for understanding these impacts.

Q-TWiST Analysis of Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma in the TIVO-3 Study.

Background: In TIVO-3, tivozanib increased progression-free survival with no difference in overall survival relative to sorafenib as third- or fourth-line therapy in patients with metastatic renal cell carcinoma. We applied quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) methods to quantify the net health benefits of tivozanib, in the presence of similar survival, when compared with sorafenib.

Methods: The mean Q-TWiST was calculated by applying utility coefficients of 0.

TiNivo: safety and efficacy of tivozanib-nivolumab combination therapy in patients with metastatic renal cell carcinoma.

Background: Treatment with tivozanib, a highly selective and potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, has demonstrated single-agent efficacy in advanced renal cell carcinoma (RCC) along with minimal off-target toxicities and a favorable adverse event (AE) profile. We report final results from TiNivo, a phase Ib/II study of tivozanib combined with nivolumab.

Patients And Methods: In phase Ib, patients with metastatic RCC received tivozanib 1.

Final Overall Survival Results from a Phase 3 Study to Compare Tivozanib to Sorafenib as Third- or Fourth-line Therapy in Subjects with Metastatic Renal Cell Carcinoma.

Tivozanib is a potent and selective inhibitor of the VEGF receptor. In an open-label, randomized phase 3 trial, we compared tivozanib to sorafenib in patients with metastatic renal cell carcinoma (mRCC) who had received two or three prior therapies. We have previously reported that the study met its primary endpoint, demonstrating an improvement in progression-free survival with tivozanib versus sorafenib (5.

Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study.

Background: Treatment for renal cell carcinoma has been revolutionised by inhibitors of VEGF receptor. Previous studies have suggested that treatment with a VEGF receptor (VEGFR) tyrosine kinase inhibitor might be effective in patients who had previous checkpoint inhibitor therapy. Therefore, TIVO-3 was designed to compare the efficacy and safety of tivozanib (a potent and selective VEGFR inhibitor) with those of sorafenib as third-line or fourth-line therapy in patients with metastatic renal cell carcinoma.

Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children.

Convection-enhanced delivery (CED) for the treatment of malignant gliomas is a technique that can deliver chemotherapeutic agents directly into the tumor and the surrounding interstitium through sustained, low-grade positive-pressure infusion. This allows for high local concentrations of drug within the tumor while minimizing systemic levels that often lead to dose-limiting toxicity. Diffuse intrinsic pontine gliomas (DIPGs) are universally fatal childhood tumors for which there is currently no effective treatment.

Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm.

Purpose: Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy.

Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer.

Purpose: This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-naïve, epidermal growth factor receptor-positive, stage IV non-small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival.

Patients And Methods: Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine.

Multicenter phase I/II study of cetuximab with paclitaxel and carboplatin in untreated patients with stage IV non-small-cell lung cancer.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have demonstrated antitumor activity in patients with non-small-cell lung cancer (NSCLC). This study examined the safety profile of the monoclonal antibody EGFR inhibitor, cetuximab, when added to paclitaxel and carboplatin in untreated patients with stage IV NSCLC. Secondary objectives included efficacy and paclitaxel and carboplatin pharmacokinetics during cetuximab treatment.

Amifostine for children with medulloblastoma treated with cisplatin-based chemotherapy.

In adult patients, amifostine appears to ameliorate cisplatin-related nephrotoxicity and ototoxicity. We assessed the safety and efficacy of amifostine in 11 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor treated with radiotherapy and vincristine, lomustine, and cisplatin. Amifostine was administered immediately prior to and 4 hr into the cisplatin infusion.

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial.

Purpose: To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer.

Patients And Methods: Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m(2), followed by 250 mg/m(2) weekly for 7 weeks.

Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor.

Purpose: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor.

Patients And Methods: Phase II, open-label clinical trial. Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation.

Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma.

Fifty-five patients with metastatic renal cell carcinoma (RCC) were treated on a multicenter, single-arm Phase II trial. Patients received single-agent Cetuximab (C225) administered by intravenous infusion at a loading dose of 400 or 500 mg/m2 followed by weekly maintenance doses at 250 mg/m2. None of the patients treated with C225 achieved either a complete or partial response.

A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma.

Purpose: Angiogenesis plays an important role in colorectal cancer progression. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in endothelial mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain-containing receptor (KDR) appear to be principally up-regulated during tumorigenesis.

A phase I study of topotecan as a radiosensitizer for brainstem glioma of childhood: first report of the Children's Cancer Group-0952.

Our purpose was to establish the maximum tolerated dosage (MTD) of daily i.v. topotecan with conventionally fractionated radiotherapy (XRT) for patients with intrinsic pontine glioma of childhood.

Safety experience with IMC-C225, an anti-epidermal growth factor receptor antibody.

In phase II trials, the anti-epidermal growth factor receptor antibody IMC-C225 did not appear to significantly exacerbate the common toxicities associated with cytotoxic chemotherapy when combined with standard anticancer treatments in patients with colorectal cancer, squamous cell carcinoma of the head and neck, or pancreatic cancer. The most common treatment-related adverse events reported during therapy with IMC-C225 were an acne-like rash and hypersensitivity reactions. The acne-like rash appeared as a sterile, suppurative form of folliculitis, commonly starting on the face, scalp, chest, and upper back.

Epidermal growth factor receptor as a therapeutic target in head and neck cancer.

Epidermal growth factor receptor (EGFR) is a cell membrane protein that is overexpressed in almost all head and neck squamous cell carcinomas. Overexpression of EGFR has been associated with a poor prognosis in head and neck tumors as well as many other malignancies. This cell membrane protein has been considered an excellent choice as an antitumor therapeutic target.

A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study.

For this study, 118 children with standard-risk acute lymphoblastic leukemia (ALL) were given randomized assignments to receive native or pegylated Escherichia coli asparaginase as part of induction and 2 delayed intensification phases. Patients treated with pegaspargase had more rapid clearance of lymphoblasts from day 7 and day 14 bone marrow aspirates and more prolonged asparaginase activity than those treated with native asparaginase. In the first delayed intensification phase, 26% of native asparaginase patients had high-titer antibodies, whereas 2% of pegaspargase patients had those levels.

Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas.

Object: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas.

Methods: Fifteen patients between the ages of 4.

Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma.

Purpose: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT).

Patients And Methods: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children.

The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma.

Objective: To determine the outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma.

Methods: Prospective analysis of 27 eyes in 22 patients with group V retinoblastoma treated with either 2- or 6-cycle chemoreduction and focal treatment methods (argon laser photocoagulation, transpupillary thermotherapy, cryotherapy, and plaque radiotherapy). The need for external beam irradiation and the eventual globe salvage rate were assessed.

Salvage therapy after postoperative chemotherapy for primary brain tumors in infants and very young children.

Background: A trend toward the use of prolonged postoperative chemotherapy, with radiotherapy deferred until relapse, has emerged for very young children with malignant brain tumors. This study was undertaken to determine the failure patterns among infants who receive such treatment and to evaluate their responses to first salvage therapy, particularly radiotherapy, after postoperative chemotherapy.

Methods: A retrospective cohort was assembled, which comprised all children younger than 36 months with biopsy-proven malignant brain tumors diagnosed during the years 1987-1993 at 3 pediatric oncology referral centers.