Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 26 Μαρτίου 2016
Population pharmacokinetic analysis of patritumab, a HER3 inhibitor, in subjects with advanced non-small cell lung cancer (NSCLC) or solid tumors
Abstract
Purpose
The purpose of this analysis was to develop a population pharmacokinetic (PK) model for patritumab, a fully human monoclonal antibody that targets human epidermal growth factor receptor 3.
Methods
A total of 833 serum concentrations were included in this analysis; serum concentrations were obtained from 145 subjects (136 with non-small cell lung cancer, nine with solid tumors) treated with patritumab [9 or 18 mg/kg intravenously every 3 weeks (q3w)] in one phase 1 and one phase 1b/2 study. Data were analyzed by nonlinear mixed-effect modeling.
Results
Patritumab PKs were best described through a two-compartment model with first-order elimination and interindividual variability on clearance (CL), volume of the central compartment (V c), distributional clearance, and volume of the peripheral compartment. In the final model, CL and V c were estimated as 0.0238 L/h and 3.62 L, respectively. Body weight (BW) and baseline albumin were found to be covariates for CL and BW was a covariate for V c. Covariates associated with hepatic and renal impairment were not significant on CL. Simulations showed that BW-based dosing reduced interindividual variability in patritumab exposure compared with fixed dosing.
Conclusions
The PK of patritumab was linear at the doses studied and well described by the two-compartment model. Hepatic and renal impairment did not appear to affect PK. Our results support BW-based dosing of patritumab on a q3w schedule.
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Role of adjuvant therapy after R0 resection for patients with distal cholangiocarcinoma
Abstract
Background
The optimal treatment strategy for cholangiocarcinoma (CC) after curative resection remains controversial. The aim of this study was to analyze the role of adjuvant therapy in R0-resected distal CC.
Methods
We retrospectively reviewed the medical records of patients who underwent R0 resection for distal CC at six cancer centers in Korea. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of the study were overall survival (OS) and recurrence-free survival (RFS).
Results
A total of 158 patients were included in the analysis; 47 patients (29.7 %) had lymph node involvement. Fifty-six patients (35.4 %) received adjuvant therapy (CT/CRT/RT: 27/20/9, respectively). Patients with advanced TNM stage (P < 0.001), T3/T4 disease (P = 0.009), positive lymph nodes (LN; P = 0.052), and elevated baseline carbohydrate antigen 19-9 (P = 0.071) were more likely to receive adjuvant therapy. The effect of adjuvant therapy varied according to treatment modality. A multivariable analysis showed a significant improvement in OS after CT [hazard ratio (HR) 0.21, 95 % confidence interval (CI) 0.08–0.53, P = 0.001] and CRT (HR 0.25, 95 % CI 0.08–0.83, P = 0.024). However, RT alone was associated with shorter OS (HR 2.38, P = 0.040), along with T3/T4 disease (HR 2.12, P = 0.012) and positive LN (HR 2.30, P = 0.008). RFS benefited from adjuvant treatment with CT (HR 0.34, P = 0.002) and CRT (HR 0.33, P = 0.004), but not with RT alone (HR 1.42, P = 0.361). In the subset analysis according to LN status, adjuvant therapy not including RT alone was associated with a significant OS and RFS advantage in both LN-negative and LN-positive patients.
Conclusions
Our results show that patients receiving CT or CRT had significant improvements in OS and RFS. In addition, a benefit of adjuvant therapy (except RT alone) was observed even in LN-negative patients.
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Overcoming treatment challenges in myelofibrosis and polycythemia vera: the role of ruxolitinib
Abstract
Myelofibrosis (MF) and polycythemia vera (PV) are BCR-ABL1-negative myeloproliferative neoplasms associated with somatic hematopoietic stem cell mutations leading to over activation of JAK–STAT signaling. MF and PV are pathogenically related and share specific clinical features such as splenomegaly and constitutional symptoms. The MF phenotype is dominated by the effects of progressive bone marrow fibrosis resulting in shortened survival. In contrast, elevated thrombosis risk due to erythrocytosis is the primary clinical concern in PV. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is approved in the USA for the treatment of patients with intermediate- or high-risk MF and patients with PV who have had an inadequate response to or are intolerant of hydroxyurea. For MF, results of two phase III studies demonstrated that ruxolitinib therapy reduced spleen volume and MF-related symptom burden, improved quality-of-life measures, and was associated with prolonged overall survival. Treatment benefits were generally sustained with continued therapy. Dose-dependent cytopenias were common but generally manageable with transfusions (for anemia), dose reduction, or treatment interruption. Optimal dosing management is critical to maintain long-term treatment benefit, because cessation of therapy resulted in rapid return of symptoms to baseline levels. Results of the phase III PV trial showed that ruxolitinib was significantly more effective than standard therapy in controlling hematocrit levels and improving splenomegaly and PV-related symptoms. Only 1 of 110 patients in the ruxolitinib arm compared with 6 of 112 patients in the control arm experienced a thromboembolic event through week 32. Grade ≥3 cytopenias were uncommon.
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Correlation between the severity of cetuximab-induced skin rash and clinical outcome for head and neck cancer patients: The XXXX experience
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Voichita Bar-Ad, Qiang (Ed) Zhang, Paul M. Harari, Rita Axelrod, David I. Rosenthal, Andy Trotti, Christopher U. Jones, Adam S. Garden, Guobin Song, Robert L. Foote, David Raben, George Shenouda, Sharon A. Spencer, Jonathan Harris, Quynh-Thu Le
PurposeThe purpose of the present study was to evaluate severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy and cetuximab.Materials & MethodsAnalysis included patients who received loading dose and ≥ 1cetuximab dose concurrent with definitive chemoradiotherapy (70Gy + cisplatin) or postoperative chemoradiotherapy (60-66Gy + docetaxel or cisplatin).ResultsSix hundred two patients were analyzed; 383 (63.6%) developed Grade 2-4 cetuximab rash. Patients manifesting Grade 2-4 rash had younger age (p<0.001), fewer pack-years smoking history (p<0.001), were more likely to be males (p=0.04), and had p16-negative (p=0.04) oropharyngeal tumors (p=0.003).In univariate analysis, Grade 2-4 rash was associated with better overall survival (OS) (hazard ratio [HR] 0.58, p<0.001) and progression-free survival (PFS) (HR 0.75, p=0.02), and reduced distant metastasis (DM) rate (HR 0.61, p=0.03), but not local-regional failure (LRF) (HR 0.79, p=0.16) relative to Grade 0-1 rash. In multivariable analysis, HRs for OS, PFS, DM, and LRF were 0.68 (p=0.008), 0.85 (p=0.21), 0.64 (p=0.06), and 0.89 (p=0.48). Grade >2 rash was associated with improved survival in p16 negative patients (HR 0.28 (0.11-0.74)) but not in p16 positive patients (HR 1.10 (0.42-2.89)) (p=0.05 for interaction). Twenty-five percent of patients with Grade 2-4 acute in-field radiation dermatitis experienced Grade 2-4 late skin fibrosis vs. 14% of patients with Grade 0-1 acute in-field radiation dermatitis (p=0.002).ConclusionGrade 2-4 cetuximab rash was associated with better survival possibly due to reduction of distant metastasis. This observation was noted mainly in p16 negative patients. Grade 2-4 acute in-field radiation dermatitis was associated with higher rate of late Grade 2-4 skin fibrosis.
Teaser
Present study evaluated the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients HNSCC treated with chemoradiotherapy and cetuximab in two prospective randomized trials. Grade 2-4 cetuximab rash was associated with better survival possibly due to reduction of distant metastasis. This observation was noted mainly in p16 negative patients. Grade 2-4 acute in-field radiation dermatitis was associated with higher rate of late Grade 2-4 skin fibrosis.from Cancer via ola Kala on Inoreader http://ift.tt/1VOapfA
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Post-Operative Spine Stereotactic Body Radiotherapy (SBRT): A critical review to guide practice
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Kristin J. Redmond, Simon S. Lo, Charles Fisher, Arjun Sahgal
Post-operative stereotactic body radiotherapy (SBRT) for metastatic spinal tumors is increasingly being performed in clinical practice. Whereas the fundamentals of SBRT practice for intact spinal metastases are established, there are as yet no comprehensive practice guidelines for the post-operative indication. In particular, there are unique considerations for patient selection and treatment planning specific to post-operative spine SBRT that are critical for safe and effective management. The purpose of this critical review is to discuss the rationale for treatment, describe those factors impacting surgical decision making, introduce modern surgical trends, and summarize treatment outcomes for both conventional post-operative conventional external beam radiotherapy and post-operative spine SBRT. Lastly, an in-depth practical discussion with respect to treatment planning and delivery considerations is provided to help guide optimal practice.
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