Bevacizumab combined with chemotherapy in the second-line treatment of metastatic colorectal cancer: results from the phase II BEVACOLOR study

BackgroundThis prospective phase II study assessed the efficacy and safety of bevacizumab plus chemotherapy regimens commonly used in the second-line treatment of metastatic colorectal cancer (mCRC).MethodsPatients with mCRC who progressed or relapsed after first-line oxaliplatin-based or irinotecan-based treatment received bevacizumab 2.5 mg/kg/week plus chemotherapy until disease progression. The primary endpoint was disease-control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety.ResultsFifty-three patients (66% men; median age, 62 years old) received second-line bevacizumab plus folinic acid, fluorouracil, and irinotecan (FOLFIRI; 57%), folinic acid, fluorouracil, oxaliplatin (FOLFOX; 26%), irinotecan (15%), or capecitabine plus irinotecan (XELIRI; 2%). The DCR was 87% (95% CI, 77%-97%); ORR was 32% (95% CI, 19%-46%). Median PFS was 6.5 months (95% CI, 5.8-7.8 months) and median OS 19.3 months, (95% CI, 14.2-25.1 months).The most frequent grade 3/4 adverse events included neutropenia (21%), diarrhea (15%), asthenia, and vomiting (9% each). Five patients (9%) had grade 3/4 targeted toxicities: grade 3 hypertension (n = 2), grade 3 venous thromboembolism (n = 2), and grade 4 arterial thromboembolism (n = 1). None of these events led to death during the study.ConclusionBevacizumab plus standard second-line chemotherapy is highly active in patients with mCRC and has an acceptable safety profile.     

Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer

Background:

A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients.

Methods:

Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit.

Results:

A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P<0.001; C6/C8, P=0.009) and satisfactory to patients (C6/C8, P=0.003) than FOLFOX-6. At the final visit, XELOX patients spent fewer days on hospital visits (3.3 vs 5.3 days, P=0.045) and lost fewer hours of work/daily activities (10.2 vs 37.1 h lost, P=0.007).

Conclusion:

XELOX has a similar QoL profile, but seemed to be more convenient in terms of administration at certain time points and reduced time lost for work or other activities compared with FOLFOX-6.     

Effects of exogenous 17β-estradiol on follicular development in the neonatal and immature mouse in vivo

Purpose

The study was aimed to examine the effects of exogenous 17??-estradiol (E₂) on oocyte nest breakdown and follicular growth in the ovary of neonatal and immature mice.

Methods

The effect of E₂ on primordial follicle formation and differentiation were examined by treating neonatal mice with E₂ in mineral oil at a dose of 10?mg/kg by sc injection each day from postnatal days 1 (PND1) to 10 (PND10). This investigation was conducted by using histological observation and immunohistochemical staining of proliferating cell nuclear antigen (PCNA); the numbers of follicles at each stage were examined to assess the follicular development.

Results

The results indicated that such dose of E₂ inhibited oocyte nest breakdown from PND1 to PND10 significantly and enhanced the oocyte staining intensity of PCNA in the ovary by PND3, 5 and 10. PCNA staining was mainly detected on growing follicles (stages later than primary follicle). Our results also revealed that E₂ decreased the size of the reproductive tract at PD10.

Conclusions

This dose of E₂ treatment inhibits oocyte nest breakdown and primordial follicle assembly, and causes follicle losses after PND5. Effects of exogenous E₂ on follicular development in the neonatal and immature mouse may through a PCNA-dependent pathway.     

Assessing the competency of University of Malaya dental graduates: employers' and graduates' perceptions

A survey was conducted to assess competencies of dental graduates of the Faculty of Dentistry, University of Malaya, as perceived by the graduates and their employers, based on the five-year undergraduate curriculum introduced in 1995. All senior dental officers in the Ministry of Health (MOH), representing employers, and all 164 dental graduates of the years 2000, 2001, and 2002 were sent a self-administered questionnaire covering eight areas of competency. The respondents had to rate these areas on a scale of 1 (very poor) to 4 (very good). The responses for each area were then dichotomized into poor (1 and 2) and good (3 and 4). If less than 60 percent of the respondents rated an area as good, then it was categorized as needing attention; 60-69 percent as satisfactory; and 70 percent and above as excellent. One hundred and six graduates (64.6 percent) and twenty-nine employers (96.7 percent) responded; of the graduates, 73.6 percent were working in the MOH and 22.6 percent in private practice. About 57.1 percent of employers reported that at least five graduates have worked under them. Graduates (85.7 percent) and employers (83.3 percent) agreed that graduates have excellent skills in communication. Although all graduates perceived their competency to be excellent in the four areas (treatment planning; community-based skills; management, administrative skills, and personal management; and professional development skills), employers felt that these are the areas that are of concern and needed attention. In conclusion, whilst generally the graduates' level of competency in almost all areas is acceptable or good, there are areas of concern that need to be addressed to further improve the five-year curriculum at the University of Malaya.     

Concurrent optic disc pit and retinal cavernous hemangioma

Letter to the editor     

Reducing hypothermia in preterm infants with polyethylene wrap

Background: Occlusive plastic applied immediately after birth to reduce evaporative heat loss has been proven effective in preterm infants <28 weeks' gestation. However its effectiveness on preterm infants >28 weeks' gestation has not been shown. This study aimed to determine the effect of occlusive wrap at birth on the temperature at neonatal intensive care unit (NICU) admission among infants of greater than or equal to 24 weeks' and less than 34 weeks' gestation. Methods: Study infants were randomly assigned to “wrap” or “control” groups. Newborns in the wrap group were wrapped with polyethylene plastic sheets within the first min after birth. Infants randomized to the control group were dried immediately after birth with warmed towels under a warmer, according to the guidelines of Neonatal Resuscitation. Infants' axillary temperatures were measured on admission to the NICU, and after having been stabilized in incubators in the NICU. Results: A total of 110 infants were recruited into the study. The mean admission temperature was significantly higher in the wrap group (35.8 vs 34.8°C, P < 0.01). Admission hypothermia (axillary temperature <36.5°C) was present in 38 (78%) and 58 (98%) infants in the wrap and control groups, respectively. Among infants of <28 weeks' gestation, the post‐stabilization temperature was significantly higher in the wrap group. Conclusions: Wrapping premature infants with gestational age <34 weeks in polyethylene plastics immediately after birth is associated with lower incidence of hypothermia.     

Is XELOX Equivalent to FOLFOX or Other Continuous-Infusion 5-Fluorouracil Chemotherapy in Metastatic Colorectal Cancer?

Continuous-infusion 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin is a frequently used regimen in metastatic colorectal cancer. Continuous-infusion 5-FU imposes constraints on patients and institutions. Oral fluoropyrimidines that mimic continuous-infusion 5-FU are now available and can be combined with oxaliplatin. In addition, it has been shown in small randomized trials that oral fluoropyrimidines are preferred by patients. Several randomized trials have compared continuous-infusion 5-FU/oxaliplatin with the oral fluoropyrimidine capecitabine plus oxaliplatin. In all of these trials, noninferiority was demonstrated for the use of oral fluoropyrimidines on the predefined endpoints such as progression-free survival, overall survival, or response rate. In all trials, however, the hazard ratios were always in favor of the use of continuous-infusion 5-FU/LV even though noninferiority was demonstrated. This could question the need to use oral fluoropyrimidines instead of continuous-infusion 5-FU. Patient preference, quality of life, and cost of treatment could also be considered in this setting, wherein most of the patients are not in a curative situation.