Revonda B. Mosher

Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) Program

Health‐compromising behaviors among survivors of childhood cancer may increase their risks of cancer recurrence and the onset of chronic disease in adulthood. Regardless of whether such behaviors occur singly or in combination with one another, multiple behavioral risk factors must be identified and addressed early to promote better health outcomes within this special population. Adolescent survivors may be especially vulnerable, as reported rates of smoking and other risky behaviors are at or near levels of their healthy peers. The psychological literature suggests stress may play a role in risk behavior initiation and maintenance, including multiple behavioral risks, and that adolescent survivors are stress‐prone. This report focuses on the prevalence and co‐occurrence of three behavioral risk factors (cigarette use, insufficient physical activity, and non‐adherence to sun protection recommendations) and describes stress‐health behavior relationships in this special population.

Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: a collaborative pediatric branch, National Cancer Institute and Children's Cancer Group trial.

PURPOSE A phase I trial of docetaxel was performed to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with refractory solid tumors. PATIENTS AND METHODS Forty-four children received 103 courses of docetaxel administered as a 1-hour intravenous infusion every 21 days. Doses ranged from 55 to 150 mg/m2, MTD was defined in heavily pretreated and less heavily pretreated (< or = 2 prior chemotherapy regimens, no prior bone marrow transplantation [BMT], and no radiation to the spine, skull, ribs, or pelvic bones) patients. RESULTS Dose-related neutropenia was the primary dose-limiting toxicity. The MTD in the heavily pretreated patient group was 65 mg/m2, but the less heavily pretreated patients tolerated a significantly higher dose of docetaxel (maximum-tolerated dose, 125 mg/m2). Neutropenia and constitutional symptoms consisting of malaise, myalgias, and anorexia were the dose-limiting toxicities at 150 mg/m2 in the less heavily pretreated patients. Thrombocytopenia was not prominent, even in patients who experienced dose-limiting neutropenia. Common nonhematologic toxicities of docetaxel included skin rashes, mucositis, and mild elevations of serum transaminases. Neuropathy was uncommon. Peripheral edema and weight gain were observed in two of five patients who received more than three cycles of docetaxel. A complete response (CR) was observed in one patient with rhabdomyosarcoma, a partial response (PR) in one patient with peripheral primitive neuroectodermal tumor (PPNET), and a minimal response (MR) in two patients with PPNET. Three of the four responding patients were treated at doses > or = 100 mg/m2. CONCLUSION The recommended phase II dose of docetaxel administered as a 1-hour intravenous infusion in children with solid tumors in 125 mg/m2. Because neutropenia was the dose-limiting toxicity and thrombocytopenia was mild, further escalation of the dose should be attempted with granulocyte colony-stimulating factor (G-CSF) support.

Late Effects in Long-Term Survivors After Treatment for Childhood Acute Leukemia

Background. This is a report of late effects in childhood cancer survivors seen in the follow-up clinic of a single institution. Materials and methods. There were 324 acute leukemia survivors in the database of the Long Term Follow Up Clinic of Childrens National Medical Center from January 1, 1997, through June 30, 2005. Results. Of the 324 acute leukemia survivors, 228 were white, 48 black, 20 Hispanic, and 12 other. Their follow-up time was 0 to 25 years (mean 5.3 years). One or more adverse events occurred in 74.1% of the 324 survivors. Defective physical growth was most commonly reported, followed by disturbed neurocognitive function, emotional difficulties, cardiac abnormalities, hypertension, osteoporosis/osteopenia, fractures, and second neoplasms. More black and Hispanic children had acute myeloid leukemia, relapses, cardiac problems, and hypertension than white and other subjects. Conclusion. Childhood cancer survivors require lifelong monitoring, with prompt identification and treatment of adverse late effects.

Growth hormone deficiency after chemotherapy for acute lymphoblastic leukemia in children who have not received cranial radiation

Chemotherapy‐related growth failure is a significant problem in children with acute lymphoblastic leukemia (ALL) and other childhood cancers. Growth impairment after cranial radiation (CR) can result in diminished adult height, but growth failure following chemotherapy without CR is usually followed by catch‐up growth and normal adult height. 1 A retrospective review of 347 ALL survivors registered in our Long Term Follow Up (LTFU) Clinic, since 1997 revealed that 109 had received CR; 3, total body irradiation (TBI); and 235, neither CR nor TBI. For patients whose growth velocity slowed, growth hormone (GH) levels and pediatric endocrinology referrals were obtained. Among the 112 ALL survivors who had received some form of CR, 5 had significant growth failure with growth hormone deficiency (GHD). Among the 235 ALL survivors treated with chemotherapy without CR, 2 were diagnosed with growth failure and GHD. We report the two survivors of childhood ALL treated with chemotherapy without CR who required GH replacement due to absence of catch‐up growth. A 15‐year‐old boy and a 12‐year‐old girl, off therapy for 9 and 6 years, respectively, were evaluated for decreased growth velocity and failure of catch‐up growth. Peak GH responses to stimulation using arginine and clonidine were 3.4 and 3.0 ng/ml, respectively (normal >10 ng/ml). Other causes of growth failure were ruled out, and GH replacement therapy was instituted. Their chemotherapy had included methotrexate, 6 mercaptopurine, vincristine, adriamycin, cyclophosphamide, L‐asparaginase, dexamethasone, cytarabine, 6 thioguanine, and intrathecal methotrexate. The growth of all children treated with intensive chemotherapy, regardless of whether CR was administered, should be closely monitored with measurement of standing height at 6 months intervals until growth is complete. Pediatr Blood Cancer 2006;46:258–261.

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 Childrens 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.

Hypertension and prehypertension in long‐term survivors of childhood and adolescent cancer

Hypertension as a late effect following childhood and adolescent cancer has received little attention. Since obesity, a known risk factor for hypertension, is increased following some childhood cancers, it seems likely that significant numbers of survivors would have hypertension.

Phase I Trial of Cisplatin and Topotecan in Children With Recurrent Solid Tumors: Children's Cancer Group Study 0942

Objectives To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cisplatin after a 72-hour continuous infusion of topotecan. Patients and Methods Thirty-six children younger than age 22 years (range 3–21) with recurrent solid tumors were treated with cisplatin 45 to 75 mg/m2 infused over the course of 6 hours, followed by a 72-hour continuous infusion of topotecan 0.75 or 1 mg/m2 per day, followed by granulocyte colony stimulating factor (G-CSF), either immediately after treatment or when neutropenia developed. Patients were stratified by the presence of bone marrow tumor involvement and previous radiation to the bone marrow. Results The DLT was neutropenia (absolute neutrophil count <500/&mgr;L for >7 days). The MTD was cisplatin 60 mg/m2 and topotecan 1 mg/m2 per day followed by G-CSF starting 24 hours after chemotherapy for patients without marrow involvement or previous radiation to the bone marrow. An acceptable MTD was not found for patients with previous radiation to the bone marrow or bone marrow involvement or without the use of G-CSF starting 24 hours after chemotherapy was completed. Topotecan clearance and steady-state levels were determined. Limited evidence for antitumor activity with this combination was found in rhabdomyosarcoma. Conclusions The recommended dose for phase II trials is cisplatin 60 mg/m2 followed by a 72-hour infusion of topotecan 1 mg/m2 per day with G-CSF starting 24 hours after the completion of topotecan.

A Phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children: A Children's Oncology Group study

This report summarizes a phase 1 study conducted by the Childrens Cancer Group (CCG) to determine the maximum tolerated dose (MTD), dose‐limiting toxicities (DLTs), pharmacokinetics, and anti‐leukemia activity of paclitaxel in children with advanced stage leukemias.

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.

Validation of a milk consumption stage of change algorithm among adolescent survivors of childhood cancer.

OBJECTIVE To assess the construct validity of a milk consumption Stages of Change (SOC) algorithm among adolescent survivors of childhood cancer ages 11 to 21 years (n = 75). METHODS Baseline data from a randomized controlled trial designed to evaluate a health behavior intervention were analyzed. Assessments included a milk consumption SOC algorithm and hypothesized theoretical and behavioral predictors of SOC. RESULTS Compared with survivors who expressed no readiness to change, those expressing readiness to change behavior for both 2 and 4 daily servings of milk reported more frequent milk consumption (P < .001), greater dietary calcium intake (P = .006), and were more likely to meet age-specific recommendations for daily calcium intake (P = .01). CONCLUSIONS AND IMPLICATIONS Results provide support for the construct validity of the milk consumption SOC algorithm relative to behavioral criteria. Research is needed to further examine algorithm validity with respect to theoretical predictors of SOC.