Osteoporosis in survivors of acute lymphoblastic leukemia.

Osteoporosis is currently receiving increasing attention as an important late effect in survivors of childhood cancer and its treatment because of their quality of life and its negative effect on the survivors' ability to perform developmentally appropriate activities. Survivors of childhood cancer are especially vulnerable because they are affected during childhood and adolescence, a time when peak bone mass should be achieved. This paper reviews decreased bone density in acute lymphoblastic leukemia (ALL), which is the most common childhood cancer and has a cure rate approaching 80%. Osteopenia/osteoporosis has been observed in all phases of the disease: at diagnosis, during treatment, and throughout the post-treatment period for as long as 20 years. Among the findings that have been described are musculoskeletal pain, disturbed gait, fractures, kyphosis, lordosis, and growth failure. Risk factors not specifically related to ALL include smoking, ingestion of carbonated beverages, and family history of "brittle bone" or fractures. Patients should be counseled in regard to diet, exercise, smoking cessation, and avoidance of carbonated beverages. There are a number of options for specific drug therapy; however, the administration of bisphosponates to children and adolescents must be approached with caution. Research is needed to determine how extensive the problem is and how to best prevent and treat the osteopenia/osteoporosis associated with ALL.

Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial.

Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase I trial was designed to determine the maximum tolerated dose, the dose-limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v. infusion for 1 h every 21 days with a starting dose of 150 mg/m2 and an escalation to 185 mg/m2 and 235 mg/m2 in subsequent patient cohorts. G-CSF (5 microg/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the post-nadir neutrophil count reached 10,000/microl. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m2. Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/1microl) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/microl), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis, back pain, asthenia, and neuropathy. One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G-CSF support in children is 185 mg/m2, which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85 % higher than the recommended adult dose.

Phase I study of topotecan administered as a 21-day continous infusion in children with recurrent solid tumors: a report from the Children's Cancer Group.

The purpose of this study was to determine the toxicity, maximum tolerated dose, and pharmacokinetics of a 21-day continuous infusion of topotecan in children with relapsed solid tumors. Fifteen patients received 40 courses of continuous ambulatory infusions of topotecan every 28 days or when there was resolution of hematological toxicity and any grade 2 or greater nonhematological toxicity. The starting dose was 0.4 mg/m2/day. Total topotecan levels were measured on days 1, 7, 14, and 21. Three of four patients who received a starting dose of 0.4 mg/m2/day experienced dose-limiting myelosuppression. At the reduced dose of 0.3 mg/ m2/day, only two of the seven patients experienced dose-limiting myelosuppression. Subsequently, four patients with more limited prior therapy were treated with 0.4 mg/m2/ day; three had dose-limiting myelosuppression. Two patients with a dose-limiting toxicity at 0.4 mg/m2/day tolerated additional courses at 0.3 mg/m2/day. An equal number of patients had grade 4 neutropenia or thrombocytopenia. Other adverse events were rare. Two patients with ependymoma, one with rhabdomyosarcoma, and one with retinoblastoma metastatic to the brain had objective responses. The steady state plasma concentration and clearance of topotecan (Css) was achieved by day 1. Css in six patients with complete data were 1.44 +/- 0.50 and 2.13 +/- 0.83 ng/ml at 0.3 and 0.4 mg/m2/day, respectively. Thus, a 21-day topotecan infusion was well-tolerated at 0.3 mg/m2/day. Myelo-suppression was the dose-limiting toxicity at 0.4 mg/m2/day. The steady state and clearance of topotecan in this study are similar to those reported in adult patients.

Late effects in survivors of bone tumors.

Today more than 71% of children with cancer are surviving their disease. This is because of improved treatment including aggressive combination therapy and better supportive care measures. The majority of patients with bone tumors are now being treated with surgery, chemotherapy, and radiation therapy, resulting in an increase in numbers of long-term survivors. This aggressive therapy, however, has increased the risk of developing late effects. This article reviews some of these late effects in survivors of bone tumors diagnosed in childhood or adolescence. Areas that are explored include cardiac, infections, second operations, second malignant neoplasms, renal, auditory, fertility, pulmonary, functional, and psychosocial outcomes. The need for long-term follow-up clinics is also addressed.

The relationship of self-concept and self-care in children with cancer.

The purposes of this descriptive study were to examine the relationships between self-concept and (a) self-care, (b) dependent-care, and (c) basic conditioning factors for children with cancer, and to compare the self-concept of children on- and off-therapy. The theoretical framework was Orem's self-care deficit theory of nursing. The sample consisted of 74 children with cancer and their mothers. Results showed small but significant correlations between variables, providing some evidence that if children had higher self-concept scores they performed more self-care activities and received more dependent-care from their mothers. The self-concept scores of the on- and off-therapy groups were not significantly different. This study supports Orem's theory and reinforces the need to promote positive self-concept.

Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children's Cancer Group.

PURPOSE: The Children's Cancer Group (CCG) undertook a phase I study (CCG-0922) to determine a tolerable dose of idarubicin given with fludarabine and cytarabine in children with relapsed or refractory leukemia. The phase I study was extended to a limited phase II study to assess the activity of this combination in children with acute myelogenous leukemia (AML). PATIENTS AND METHODS: This was a multiinstitutional study within the CCG. Eleven patients were entered onto the phase I study: seven with AML, three with acute lymphoblastic leukemia (ALL), and one with chronic myelogenous leukemia (CML). The maximal-tolerated dose (MTD) of fludarabine and cytarabine determined in a previous study was a fludarabine loading dose (LD) of 10.5 mg/m2 followed by a continuous infusion (CI) of 30.5 mg/m2/24 hours for 48 hours, followed by cytarabine LD 390 mg/m2, then CI 101 mg/m2/h for 72 hours. Idarubicin was given at three dose levels: 6, 9, and 12 mg/m2 intravenously (I.V.) on days 0, 1, and 2. The phase II portion of the trial included 10 additional patients with relapsed or refractory AML. RESULTS: A dose of idarubicin 12 mg/m2/d for 3 days given in combination with fludarabine and cytarabine was tolerated. The major toxicity encountered was hematologic. Nonhematologic toxicities included transaminase elevations, hyperbilirubinemia, and infections. Eight of 10 patients with AML in the phase II portion (12 mg/m2 idarubicin) achieved a complete remission (CR). CONCLUSION: This combination is active in patients with relapsed or refractory AML. The major toxicity encountered is hematologic. This regimen may be useful therapy for AML and should be compared with standard induction therapy in children with newly diagnosed AML.

Adjustment responses of children and their mothers to cancer: self-care and anxiety.

PURPOSE/OBJECTIVES: To examine children's and their mothers' adjustment responses (self-care and anxiety) to cancer. DESIGN: A descriptive multivariate study. SETTING: Two metropolitan pediatric oncology clinics. SAMPLE: A nonprobability sample of 74.9-18 year olds diagnosed with cancer and their mothers. METHOD: Children completed two questionnaires--the Children's Self-Care Performance Questionnaire and Children's State-Trait Anxiety Inventory. Mothers completed the Dependent Care Agent Performance Questionnaire, the State-Trait Anxiety Inventory, and a demographic data form. FINDINGS: Multivariate analysis of variance indicated that children off therapy and their mothers had better adjustment responses than those on therapy. Basic conditioning factors significantly predicted children's self-care practices and state and trait anxiety as well as mothers' dependent-care and state anxiety. A significant canonical correlation surfaced between the set of children's adjustment responses and the set of mothers' adjustment responses. CONCLUSIONS: Children who have completed treatment for cancer and their mothers have better adjustment responses than those still receiving therapy. Basic conditioning factors predict adjustment responses, and a relationship exists between the adjustment responses of children and those of their mothers. IMPLICATIONS FOR NURSING PRACTICE: Further research is needed to investigate children's self-care practices, determine mothers' dependent-care practices, and compare children with cancer to a normative sample. In clinical practice nurses must consider the profound effect of cancer on the mother and child the anxiety levels of children with cancer and their mothers, and the influence of these individuals on each other.