Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol.

BACKGROUND: We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more. PATIENTS AND METHODS: Data from 52 patients with HSRs were analyzed according to the Common Toxicity Criteria for Adverse Events (CTCAE), v3.0. Three patients were chosen for the desensitization protocol. After determining the starting point for desensitization, we applied the standard protocol for parenteral desensitization to b-lactam antibiotics. Oxaliplatin treatment was then carried out with serial 10-fold dilutions in sufficient volume to administer the total dose. A total of 52 patients (24.2%) were recorded as having an allergic reaction to oxaliplatin. RESULTS: Hypersensitivity reactions were recorded after a mean of 6.5 (SD +/- 4.5) cycles. Only 4 patients (4 of 215; 1.8%) developed CTCAE grade 3/4 HSRs. Hypersensitivity reactions were seen more likely in patients receiving second-line or more of chemotherapy compared with chemotherapy-naive patients. No other correlations were seen (the presence of atopic disease, positive skin prick test). The 3 patients, having completed the parenteral desensitization protocol, completed their treatment uneventfully as well. CONCLUSION: Hypersensitivity reactions from oxaliplatin respond quickly to the discontinuation of the drug and appropriate support. Premedication and an increased infusion time could allow for readministration. The desensitization protocol we developed can provide a reliable alternative to permanent discontinuation of oxaliplatin.

Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol.

Background: We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more. Patients and Methods: Data from 52 patients with HSRs were analyzed according to the Common Toxicity Criteria for Adverse Events (CTCAE), v3.0. Three patients were chosen for the desensitization protocol. After determining the starting point for desensitization, we applied the standard protocol for parenteral desensitization to b-lactam antibiotics. Oxaliplatin treatment was then carried out with serial 10-fold dilutions in sufficient volume to administer the total dose. A total of 52 patients (24.2%) were recorded as having an allergic reaction to oxaliplatin. Results: Hypersensitivity reactions were recorded after a mean of 6.5 (SD +/- 4.5) cycles. Only 4 patients (4 of 215; 1.8%) developed CTCAE grade 3/4 HSRs. Hypersensitivity reactions were seen more likely in patients receiving second-line or more of chemotherapy compared with chemotherapy-naive patients. No other correlations were seen (the presence of atopic disease, positive skin prick test). The 3 patients, having completed the parenteral desensitization protocol, completed their treatment uneventfully as well. Conclusion: Hypersensitivity reactions from oxaliplatin respond quickly to the discontinuation of the drug and appropriate support. Premedication and an increased infusion time could allow for readministration. The desensitization protocol we developed can provide a reliable alternative to permanent discontinuation of oxaliplatin.

Reproducibility of home and ambulatory blood pressure in children and adolescents.

OBJECTIVE: To evaluate the reproducibility of blood pressure measured at home (HBP) in comparison with ambulatory (ABP) and clinic blood pressure (CBP) in children and adolescents. PARTICIPANTS AND METHODS: Individuals aged 8-17 years who had been referred for elevated CBP were included. CBP was measured at two visits, HBP on 5 days and ABP for 24 h. A second session including all the above measurements was performed after 8 weeks. The reproducibility of CBP (second visit of each session), HBP (average of days 2-5 of each session) and ABP (average 24-h, awake and asleep) was quantified using test-retest correlations coefficients (r) and the standard deviation of differences (SDD) between repeated measurements. RESULTS: Sixteen individuals were included [mean age 13.3+/-2.9 (SD)] years, range 8-17, nine boys]. According to Task Force CBP criteria, eight were classified as hypertensives, three as high normal and five as normotensives. The reproducibility of HBP (systolic/diastolic r, 0.74/0.82, SDD 7.0/4.3) was superior to that of CBP (r, 0.63/0.80, SDD 10.4/6.3). However, ABP appeared to provide the most reproducible values (r, 0.87/0.84, SDD 5.5/4.3 for 24-h ABP; r, 0.85/0.76, SDD 5.9/5.0 for awake; r, 0.76/0.79, SDD 7.0/5.0 for asleep ABP). Aspects of the diurnal ABP variation were poorly reproducible (r, 0.62/0.14, SDD 6.8/5.5 for awake-asleep ABP difference; r, 0.55/0.26, SDD 0.07/0.11 for awake : asleep ratio). CONCLUSION: These data suggest that in children and adolescents home blood pressure measurements are more reproducible than clinic measurements. However, 24-h ambulatory monitoring appears to provide the most reproducible blood pressure values.

White-coat hypertension and masked hypertension in children.

The use of ambulatory blood pressure monitoring in addition to the conventional office measurements makes possible the detection of individuals with white-coat hypertension and masked hypertension. In children referred for elevated blood pressure, both these phenomena appear to be common (10-15% for each). In a population of healthy children, white-coat hypertension appears to be as common as hypertension, whereas masked hypertension appears to be more common than white-coat hypertension or hypertension. In children with persistent white-coat or masked hypertension, assessment of target organ damage by echocardiography is required. Preliminary evidence suggests that, in contrast to white-coat hypertension, which is not associated with target organ damage, masked hypertension in children is associated with increased left ventricular mass. Children with masked hypertension should be followed up and possibly treated for hypertension if the phenomenon persists or there is evidence of target organ damage.

Office and out-of-office blood pressure measurement in children and adolescents.

Office and out-of-office blood pressure measurements are being used for the diagnosis of hypertension in children and adolescents. The US National Heart, Lung, and Blood Institute have recently presented a new classification of blood pressure. On the basis of office measurements the 90th, 95th and 99th percentile for gender, age and height are used to classify children and adolescents as normotensive, pre-hypertensive and stage-1 or stage-2 hypertensive. Although auscultation using a standard mercury sphygmomanometer remains the recommended method, accumulating evidence suggests that ambulatory blood pressure monitoring is useful for the detection of white-coat hypertension and the prediction of target organ damage in children and adolescents. Studies have shown ambulatory blood pressure to be more reproducible than office measurements and normative tables for ambulatory measurements have been developed from cross-sectional studies in children and adolescents. In regard to home measurements in children, there are limited data from small trials showing lower blood pressure levels than daytime ambulatory blood pressure. In conclusion, ambulatory blood pressure monitoring is already finding a role as a supplementary source of information in children and adolescents, whereas at present home measurements should not be used for decision making in this population.

Out-of-office blood pressure in children and adolescents: disparate findings by using home or ambulatory monitoring.

BACKGROUND: The validity of home blood pressure (HBP) measurements in children has not been evaluated, although in clinical practice such measurements are being used. This study compares HBP, with clinic (CBP) and daytime ambulatory blood pressure (ABP) in children and adolescents. METHODS: Fifty-five children and adolescents aged 6 to 18 years were evaluated with CBP (three visits), HBP (6 days), and daytime ABP. Mean age was 12.3 +/- 2.9 (SD) years, 33 boys. According to the Task Force CBP criteria, 26 were hypertensives, 6 had high-normal BP (hypertensive group), and 23 were normotensives (normotensive group). RESULTS: In the hypertensive group, CBP was 130.8 +/- 7.6/72.5 +/- 8.1 mm Hg (systolic/diastolic), HBP 118.9 +/- 6.3/73.7 +/- 6.7, and ABP 130.8 +/- 8.1/75.5 +/- 8.3. In the normotensive group, CBP was 112.8 +/- 8/63.1 +/- 6.3, HBP 106.7 +/- 8.4/67.2 +/- 5.2, and ABP 123.9 +/- 7.2/72 +/- 4.3. Strong correlations (P < .001) were observed between CBP-HBP (r = 0.73/0.57, systolic/diastolic), CBP-ABP (r = 0.59/0.49), and HBP-ABP (r = 0.72/0.66). In normotensive subjects, ABP was higher than both CBP and HBP for systolic and diastolic BP (P < .001). Furthermore, systolic HBP was lower than CBP (P < .01), whereas the opposite was true for diastolic BP (P < .05). In hypertensive subjects systolic HBP was lower than both CBP and ABP (P < .001), whereas CBP did not differ from ABP. For diastolic BP no differences were found among measurement methods. CONCLUSIONS: These data suggest that, in contrast to adults in whom HBP is close to the levels of daytime ABP, in children and adolescents HBP appears to be significantly lower than daytime ABP. Until more data become available, caution is needed in the interpretation of HBP in children and adolescents.

Home or self blood pressure measurement? What is the correct term?

OBJECTIVE: Blood pressure measurements taken by patients at home (HBP) are usually referred to as 'self' or 'home' measurements. To demonstrate the most appropriate term we compared self-home measurements (S-HBP), with home measurements taken by relatives (R-HBP), clinic measurements taken by physicians (P-CBP) and self-measurements in the clinic (S-CBP). PATIENTS AND METHODS: Thirty treated hypertensives were randomized to an initial clinic BP (CBP) monitoring period (week 1, P-CBP followed by S-CBP measurements, or the opposite; 1 visit each), then to a HBP monitoring period (weeks 2-3, S-HBP followed by R-HBP or the opposite; 3 workdays each), and finally to a second CBP monitoring period (week 4, S-CBP followed by P-CBP, or the opposite). Triplicate morning trough measurements were taken per occasion using the same fully automated device. RESULTS: There was no difference between S-CBP and P-CBP (mean difference -1.9 +/- 6.1 mmHg, 95% confidence interval (CI) -4.2, 0.4/-1.6 +/- 4.7, 95% CI -3.3, 0.2, systolic/diastolic), or between S-HBP and R-HBP (-0.9 +/- 6.9, 95% CI -3.5, 1.8/-0.4 +/- 4.3, 95% CI -2.0, 1.2). S-CBP was higher than S-HBP (mean difference 9.3 +/- 9.0/4.9 +/- 5.4 mmHg, systolic/diastolic, P < 0.001) and R-HBP (8.4 +/- 9.1/4.5 +/- 5.0, P < 0.001). P-CBP was also higher than S-HBP (11.2 +/- 11.9/6.5 +/- 6.8, P < 0.001) and R-HBP (10.3 +/- 11.2/6.1 +/- 6.5, P < 0.001). CONCLUSIONS: Self-measurements provide similar BP levels to measurements taken by relatives or physicians, provided that measurements are taken in the same setting. 'Self-BP' is a misnomer because self-measurement has no impact on the difference between home and clinic BP. Given that this difference can be exclusively attributed to the effect of the different setting, the term 'home BP' represents a more appropriate term.