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PubMedDate not supplied

Pharmacogenetics and pediatric cancer.

The great advances in therapeutic success for childhood cancers have provided the impetus for strategies to avoid serious systemic toxicities from chemotherapy. This review describes the impact of genetic mutations in drug metabolism pathways on the toxicity of anticancer agents. Although many polymorphisms have been related to toxicity in adults, these associations are less well defined in children. The role of genetic polymorphisms in MTHFR, TYMS, TPMT, and UGT1A1 in influencing drug toxicity is reviewed. Better understanding of the pharmacogenetic determinants of drug metabolism or pharmacologic cofactors may allow for prospective identification of potential patients who are at increased risk for toxicity, allowing for dose optimization and resulting in a decrease in toxic risk while maximizing efficacy.

Antineoplastic Agents↗
PubMedDate not supplied

Evaluating survivors of pediatric cancer.

The past 3 decades have seen tremendous improvements in the survival of children diagnosed with cancer, with the 5-year survival rate approaching 80%. This improvement in survival has resulted in a growing population of childhood cancer survivors. Use of cancer therapy at an early age can produce complications that may not become apparent until years later. Approximately two thirds of the survivors of childhood cancer experience at least one late effect and about one fourth experience a late effect that is severe or life-threatening, although psychosocial issues in survivors and family members are often underestimated and may be more prevalent. Long-term complications in childhood cancer survivors, such as impairment in growth and development, neurocognitive dysfunction, cardiopulmonary compromise, endocrine dysfunction, renal impairment, gastrointestinal dysfunction, musculoskeletal sequelae, and subsequent malignancies, are related not only to the specific therapy used but also may be determined by individual host characteristics. We review the known late effects in survivors of childhood in order to suggest reasonable starting points for the evaluation of specific long-term problems in this unique but growing population.

Antineoplastic Agents↗
PubMed2004

Antibiotic lock with vancomycin and urokinase can successfully treat colonized central venous catheters in pediatric cancer patients.

We used an antibiotic lock technique with vancomycin in combination with urokinase in 10 consecutive eligible children with Gram-positive catheter-related bacteremia persisting after appropriate intravenous antibiotics. Treatment was successful in sterilizing all colonized central venous catheters, avoiding device removal and delay of further chemotherapy. The antibiotic lock technique may represent a safe and effective therapeutic option in patients with selected, uncomplicated catheter-related bacteremias resistant to systemic antimicrobial therapy, particularly when maintaining a venous access is mandatory.

Adolescent↗
PubMed1997

Nutrition and pediatric cancer.

Good nutritional status is very important in patients with malignant diseases, especially during chemotherapy. It is most important to avoid cachexia: One should avoid factors that may cause it or feed the patient by tube or intravenously if not possible orally, even if it is necessary to give total parenteral nutrition. The target is to ensure that the infants and children with malignant diseases during chemotherapy will retain optimal nutritional condition, which helps the children's growth development and helps them tolerate the treatment better. As the patient's age changes, so the need for certain nutritive materials is modified, and the usage is changed also.

Adolescent↗
PubMed1979

Pediatric cancer survival and marriage: issues affecting adult adjustment.

Of 36 men and women, now aged 21 or older, who were treated for cancer as children, 20 have married. As part of a long-term follow-up, 13 of their spouses were interviewed about the effects of cancer on the patient and on their marriage. Comparison of patient's physical limitations, visible impairments, and psychiatric adjustment ratings indicated significant differences between patients who have married or become engaged and those who have not married.

Adaptation, Psychological↗
PubMed1988

After treatment ends: psychosocial sequelae in pediatric cancer survivors.

Fifty-two survivors of childhood cancer and their families were assessed by questionnaire and interview to determine survivors' psychosocial status two years or more after treatment. Most were functioning well and serious psychosocial problems were relatively rare. Communication patterns during treatment were most predictive of psychosocial outcome whereas indicators of medical severity were least predictive. The heterogeneity of effective coping styles, appropriate to varied personality types, was noted.

Adolescent↗
PubMed2004

High-throughput detection of glutathione s-transferase polymorphic alleles in a pediatric cancer population.

Polymorphisms of glutathione S-transferase (GST) enzymes have been correlated with altered risk of several cancers, as well as altered response and toxicity from cancer chemotherapy. We report a low cost, highly reproducible and specific PCR-based high-throughput assay for genotyping different GSTs designed for use in large clinical trials. In comparison to an alternative genotyping method (single nucleotide extension), the sensitivity and specificity of the high throughput assay was shown to be 92 and 97%, respectively, depending on the source of genomic DNA. Using the high-throughput assay, we demonstrate by multivariate analysis an increased risk of acute lymphoblastic leukemia, glial brain tumors, and osteosarcoma for patients carrying nonnull alleles of GSTM1 and/or GSTT1.

Antineoplastic Agents↗
PubMed1980

Visible physical impairment and psychological adjustment among pediatric cancer survivors.

Because psychological and psychiatric assessments of childhood cancer survivors have revealed a high rate of psychiatric sequelae, the authors investigated the relationship between the degree of physical unpairment resulting from cancer treatment and the psychosocial adjustment problems of survivors. Ratings of physical impairment were based on the visibility of physical residua as well as the functional limitations they imposed. The results indicated that the psychosocial adjustment of survivors is not significantly related to the severity of physical impairment.

Adaptation, Psychological↗
PubMed2006

Family impact of neurodevelopmental late effects in survivors of pediatric cancer: review of research, clinical evidence, and future directions.

Children and adolescents who have survived childhood cancer are vulnerable to late effects of their disease and treatment experience, including both physical and psychological sequelae. The neurodevelopmental (ND) sequelae (e.g., difficulties with attention, memory, information processing, and other executive functions) faced by children surviving central nervous system (CNS) cancers or CNS treatments can have a range of effects on their psychological adjustment and quality of life as they reintegrate into school and social settings. Survivors facing such difficulties may be influenced by their family environment, and these struggles may in turn impact the perceived burden of their parents and family system, suggesting a bidirectional framework for understanding the impact of ND late effects within the family. The current study summarizes the following: Findings of family outcomes in children with ND late effects of cancer treatment; evaluation of methodological and measurement issues; the importance of examining bidirectional family-child influences; and implications for future survivorship research and clinical care addressing the role of ND late effects from a systems perspective.

Child↗
PubMed1993

Escalating teniposide systemic exposure to increase dose intensity for pediatric cancer patients.

PURPOSE: The primary objective for this study was to determine whether controlling pharmacokinetic variability, by designing patient-specific dosage regimens for teniposide using a Bayesian estimation control strategy, would permit an increase in dose intensity without increased toxicity. PATIENTS AND METHODS: Twenty patients with relapsed acute lymphocytic leukemia were given teniposide as part of their induction and maintenance therapy. Before beginning reinduction therapy, an intensive pharmacokinetic study was performed based on 12 measured teniposide plasma concentrations. Doses were determined to achieve a targeted systemic exposure defined by an area under the plasma concentration time curve (AUC) beginning at an AUC consistent with that predicted for a patient with average pharmacokinetic parameters receiving the currently accepted maximal-tolerated dose. The targeted systemic exposure was then escalated in increments of 25% in cohorts of at least three patients until unacceptable toxicity occurred. In 36 follow-up studies, when teniposide was administered during maintenance therapy, a Bayesian strategy based on only three or five measured drug concentrations was evaluated for precision and bias for achieving the targeted systemic exposure against the full pharmacokinetic study. RESULTS: Teniposide clearance varied over a fivefold range (3.7 to 21.6 mL/min/m2). With the use of the patient-specific dosage regimens, the intensity of systemic exposure was increased 50% (1,656 mumol.h v 1,060 mumol/L.h) over that previously possible with standard fixed doses, with no increase in acute, nonhematologic toxicity. Teniposide concentrations (n = 265) were well predicted (R2 = .82) with as few as three measured values from the initial study. CONCLUSION: Targeting systemic exposure is clinically feasible, precise, and allows increased dose intensity for teniposide without increased risk of acute, nonhematologic toxicity, when compared with fixed-dose regimens.

Adolescent↗