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Chemotherapy-induced nausea and emesis in pediatric cancer patients: an analysis of coping strategies.

We investigated the preference and perceived efficacy of coping strategies used to manage chemotherapy-induced nausea and emesis in 57 pediatric oncology patients. Over 85% of children preferred "Wishful Thinking," "Emotional Regulation," and "Distraction" to cope with nausea, and "Emotional Regulation" to manage emesis. Stepwise logistic regression analyses revealed that the coping strategy used and its perceived efficacy depended upon patient age and gender, severity of symptom distress, time elapsed from last chemotherapy, experience, and whether nausea or emesis was the identified problem. Successful copers, defined as those reporting high coping efficacy and minimal distress, composed only 25% of the sample. These children most often used "Problem Solving" combined with "Social Support" for symptom management. Successful coping was also associated with lower emetogenic potential of chemotherapy. The significance of these results is discussed for identifying high-risk children who may benefit from coping interventions.

Adaptation, Psychological↗

Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients.

GOALS: Candidemia is a serious infection that can severely complicate the care of children with cancer. We sought to determine the spectrum of Candida species in children with cancer, since effective therapy may depend on the species involved. PATIENTS AND METHODS: A retrospective review of candidemia episodes in our pediatric oncology patients over a 9-year period was conducted. During this period azole prophylaxis was not routine in this group. RESULTS: 38 episodes of candidemia were identified: C. albicans 29%, C. tropicalis 26%, C. parapsilosis 24%, C. krusei 8%, C. glabrata 8%, and C. lusitaniae 5%. Non-albicans Candida was common in patients not receiving azole prophylaxis. Species typically susceptible to azoles were common among patients not using azoles. Death attributed to the fungal infection occurred in 21% of episodes, with nearly all the deaths occurring in patients with C. albicans and C. tropicalis. CONCLUSIONS: C. albicans is not the predominant species in pediatric oncology patients experiencing candidemia, even in azole-naive patients.

Adolescent↗

Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

BACKGROUND: Nausea and vomiting are among the most unpleasant adverse side effects of cancer therapy. PROCEDURE: An open-label dose-escalation study was conducted to assess the appropriate intravenous dose of dolasetron for pediatric patients undergoing chemotherapy. Patients received dolasetron in single intravenous doses of 0.6 (n = 10), 1.2 (n = 12), 1.8 (n = 12), or 2.4 (n = 12) mg/kg 30 min before receiving emetogenic chemotherapy. Pharmacokinetic parameters were evaluated at each dose level and efficacy was evaluated over the first 24 hr following the administration of dolasetron. RESULTS: A complete response was achieved in 10% of patients given 0.6 mg/kg, 25% of patients given 1. 2 mg/kg, 67% of patients given 1.8 mg/kg, and 33% of patients given 2.4 mg/kg. Peak plasma concentrations (Cmax) were observed between 0. 33 and 0.75 hr following dolasetron infusion. Cmax and area under plasma concentration-time (AUC) increased with larger doses of dolasetron, while terminal disposition half-life (t1/2) and apparent clearance (Clapp) were not significantly changed with respect to dose. For 1.8-mg/kg dolasetron, the t1/2 was 4.98 hr and the maximum plasma concentration (tmax) 0.47 hr. Adverse events were mild to moderate. No serious events occurred. Conclusions. This study suggests that a single intravenous dose of 1.8 mg/kg is the optimum single intravenous dose for controlling chemotherapy-induced emesis in pediatric patients.

Adolescent↗

In vitro study of in line filtration of medications commonly administered to pediatric cancer patients.

Intravenous administration of drugs commonly used in patients with acute nonlymphocytic leukemia was simulated using a .22 micrometers air-eliminating filter. Drug concentrations were measured pre- and postfiltration using standard pediatric drug doses and concentrations. The percentage of administered dose recovered in the postfilter sample for chemotherapy drugs was adriamycin, 92%; dactinomycin, 87%; cytarabine, 96%; and vincristine, 90%. For antibiotics, the per cent recovery was carbenicillin, 90%; cephalothin, 96%; and gentamicin, 38%. Gentamicin, and perhaps other drugs evaluated, should not be administered through a filter of the type used in this study.

Anti-Bacterial Agents↗

Phase I study of ICRF-187 in pediatric cancer patients and comparison of its pharmacokinetics in children and adults.

A phase I study of ICRF-187 as a 2-hour iv infusion daily for 3 days was conducted in 46 evaluable pediatric patients. The maximum tolerated dose was 3500 mg/m2/day X 3 based on changes in hepatic function and coagulation abnormalities encountered when larger dosages were administered. One patient with acute lymphocytic leukemia achieved a complete remission and four cleared the blood of lymphoblasts. No other objective responses were seen. Pharmacokinetic analysis showed that the children had a larger volume of distribution per kilogram of body weight in the central compartment and total body and a more rapid total-body clearance than adults. These parameters can explain only part of the increased tolerance of children to ICRF-187.

Adolescent↗

Pharmacokinetics of anti-ganglioside GD2 mAb 14G2a in a phase I trial in pediatric cancer patients.

A phase I trial of a murine anti-ganglioside (GD2) monoclonal antibody (mAb) 14G2a was conducted in 14 neuroblastoma patients and 1 osteosarcoma patient to assess its safety, toxicity and pharmacokinetics in pediatric patients. The pharmacokinetics of mAb 14G2a were biphasic with a t alpha 1/2 of 2.8 +/- 2.8 h and a t beta 1/2 of 18.3 +/- 11.8 h. In general, t beta 1/2 was dose-dependent with a level of significance of P = 0.036, and it reached a plateau at doses of 250 mg/m2 or more. Overall the peak serum levels were dose-dependent at P < 0.001. However, they demonstrated an abrupt increase between doses of 100 mg/m2 and 250 mg/m2. The latter two suggest a saturable mechanism for mAb elimination. In addition, peak serum concentrations were observed earlier at higher mAb doses, which indicates the achievement of a steady state. The t beta 1/2 of mAb 14G2a in children appears to be shorter than in adults. Furthermore, 2 patients demonstrated a considerable decrease in t beta 1/2 following retreatment with 14G2a. This was paralleled by high human anti-(mouse Ig) antibody levels. This study represents the first comprehensive analysis of murine mAb pharmacokinetics in children and will be useful in the future design of mAb therapy.

Adolescent↗

Urine protein analysis by gel electrophoresis and laser densitometry after chemotherapy in pediatric cancer patients.

A common side effect of chemotherapy is reversible or nonreversible nephrotoxicity. SDS polyacrylamide gel electrophoresis combined with laser densitometry was evaluated as a suitable method to analyze pathologic urine proteins. A total of 52 pediatric patients were followed during and 63 patients were followed after therapy. During therapy renal damage was recorded in 43% of the leukemia patients, in 56% of nephroblastoma patients, and 75% of patients with other tumors. Three or more months after therapy pathologic patterns were seen in 25% of acute lymphoblastic leukemia patients, in 35% of patients with nephroblastoma, and in 62% of other patients. Patients with persistent complete tubular proteinuria and mixed glomerular/tubular proteinuria were found to have a high risk for irreversible renal damage and should be controlled periodically. This method permits a rapid and reliable analysis of urine proteins and is suitable for follow-up tests of renal function during and after chemotherapy.

Adolescent↗

Molecular determinants of differential sensitivity to docetaxel and paclitaxel in human pediatric cancer models.

BACKGROUND: The differential sensitivity of some tumors to paclitaxel and docetaxel raises questions regarding the specific mechanisms responsible for the discrepant sensitivity to these taxanes. MATERIALS AND METHODS: Docetaxel and paclitaxel were evaluated and compared at maximum tolerated doses (MTD) and 0.5 MTDs against the human pediatric tumor xenograft models SK-N-MC and IMR32 (neuroblastoma), RH1 and RH30 (rhabdomyosarcoma) and KHOS/NP (osteosarcoma), with 8-10 animals per group. The drug effects on the expression of the beta-tubulin isotypes, Bcl-2, Bax, Bcl-XL and proteomic profiles were evaluated by immunobloting and SELDI mass spectrometry in tumor xenografts dosed at 0.5 MTDs. RESULTS: At MTDs, docetaxel was superior in neuroblastoma and osteosarcoma, while paclitaxel was more active in the rhabdomyosarcoma models. Docetaxel showed remarkable efficacy in KHOS/NP even at 0.5 MTD. The drugs had significantly different, yet highly heterogeneous effects on the tumor levels of betaI-tubulin (RH30), betaIII-tubulin (IMR32, KHOS/NP, RH]), Bax (IMR32, SK-N-MC) and Bcl-XL (KHOS/NP). In contrast, six protein species identified by proteomic profiling were consistently and differentially regulated by docetaxel and paclitaxel in all KHOS/NP xenografts. CONCLUSION: Anticancer activity showed no apparent correlation with drug effects on beta-tubulin isotypes and apoptotic markers. The mass spectrometry approach has potential for the discovery of proteomic biomarkers for drug sensitivity.

Animals↗

Dexrazoxane for the prevention of cardiomyopathy in anthracycline treated pediatric cancer patients.

Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent that binds iron intracellularly, has been cautiously included in anthracycline-based regimens. Our understanding of anthracycline and dexrazoxane pharmacokinetics in children is very limited. In addition, the administration schedule used for adults (bolus dexrazoxane prior to bolus anthracycline) may not be the best to attain both short- and long-term cardioprotection. Dexrazoxane could diminish the anti-tumor activity of and/or increase toxicities from anthracyclines. Pediatric oncologists must be assured this intervention does not diminish the success in curing children with cancer.

Anthracyclines↗