Phase II Study of Panitumumab Monotherapy in Chemotherapy‐Naïve Frail or Elderly Patients with Unresectable RAS Wild‐Type Colorectal Cancer: OGSG 1602

Lessons Learned

• Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
• It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.

BackgroundFirst‐line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy‐naïve frail or elderly patients with unresectable RAS wild‐type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first‐line treatment.MethodsWe conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.ResultsThirty‐six patients (median age: 81 [range, 67–88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty‐three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty‐eight patients (77.8%) had left‐sided CRC, whereas eight (22.2%) had right‐sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4–67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5–87.7). The RR of patients with left‐ and right‐sided tumors was 65.4% (95% CI, 44.3–82.8) and 0.0% (95% CI, 0.0–36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).ConclusionPanitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Survey of Japanese dermatological vasculitis specialists on cases of cutaneous arteritis (cutaneous polyarteritis nodosa)

We developed a questionnaire to examine the findings of cutaneous arteritis among dermatological specialists experienced in vasculitis as certified by the Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. We sent a questionnaire to 12 dermatological facilities identified through the revised Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. Retrospective data obtained from 84 patients at the 12 dermatological facilities between 2012 January 2016 December were evaluated. The 84 patients were categorized into two groups, a systemic steroid treatment group (group 1, n = 52) and a no systemic steroid treatment group (group 2, n = 32). C-reactive protein in group 1 patients was significantly higher than that in group 2 patients. Frequency of fever, arthritis, myalgia- and peripheral neuropathy in group 1 was significantly higher than that in group 2. We propose that these symptoms could serve as early markers for the transfer from cutaneous arteritis to systemic polyarteritis nodosa. We further suggest that patients who are subsequently associated with cerebral hemorrhage and infarction, who are originally diagnosed as having cutaneous arteritis, could progress to systemic polyarteritis nodosa. The study demonstrated that it is important for dermatologists to detect these findings early in order to establish an accurate diagnosis and a timely treatment.     

Removal methods of rigid stylets to minimise adverse force and tracheal tube movement: a mathematical and in-vitro analysis in manikins

This study investigated displacement of the tracheal tube caused by different methods of intubating stylet removal, using in-vitro experiments and mathematical analysis. In the first in-vitro experiment, we measured the distance travelled by the tube tip during stylet extraction. Then, we investigated the ideal technique for stylet extraction using mathematical analysis, which would cause minimal tube displacement. Then, using a training manikin, we measured the force applied to the vocal cords and stylet extraction force during tracheal intubation. When the stylet was extracted along a straight path towards the stylet end, the distance travelled by the tube tip significantly increased as the bending angle increased. Mathematical analysis revealed that the stylet should be diagonally extracted (in the sagittal plane) at an appropriate angle, rather than along a straight path towards the direction of the stylet end. In simulated tracheal intubation, extraction force and force applied to the vocal cords both significantly increased as the bending angle increased. Compared with the ‘hockey stick’-shaped stylet, the arcuate-shaped stylet resulted in reduced force. Our results indicate the potential risk for vocal cord injury when using hockey stick-shaped stylets with large bending angles.     

Effect of single bout downhill running on the serum irisin concentrations in rats

Abstract

This study aimed to characterize the effect of different running modes on serum irisin concentrations in rats. A total of 18, 10-week-old rats were divided into three groups; control group, 16° uphill running group (concentric exercise; CON) and, ?16° downhill running group (eccentric exercise; ECC). The running group’s rats ran on the inclined treadmill at 16?m/min, for a total of 90?min. Blood was drawn from the rats, 48?h after running, after which the rats were anesthetized. The serum concentrations of irisin were measured using enzyme-linked immunosorbent assays. Vastus intermedius was collected for immunohistochemical analysis. After multiple comparisons, the ECC showed a significantly high serum irisin concentration (ECC: 28.42?±?6.31?ng/ml, CON: 21.27?±?3.03?ng/ml) and a larger irisin antibody reactive cross-sectional area in vastus intermedius compared to the CON (p?<?0.05). This is the first study to reveal that single bout downhill running increases serum irisin concentrations in rats.     

Oncolytic Virus Therapy with HSV-1 for Hematological Malignancies

1. Download : Download high-res image (99KB)
2. Download : Download full-size image