Bleomycin (Blenoxane) and cisplatin (Platinol) are two anticancer drugs with activity for head and neck tumors. Introduced into clinical use in the past ten years, bleomycin is used primarily in the chemotherapy of squamous cell carcinomas, lymphomas, and testicular carcinoma, while cisplatin is effective against testicular and ovarian carcinoma, head and neck cancer, bladder cancer, and neuroblastoma. Bleomycin is rapidly excreted renally (T 1/2 beta = 2-4 hr) although enzymatic inactivation also occurs in many tissues. Cisplatin is nonenzymatically converted to highly protein-bound metabolites, which then undergo renal elimination, but total body clearance occurs much more slowly than with bleomycin (T 1/2 beta = 40-50 hr). Both agents have acute and chronic toxicities; the acute toxicities are generally reversible but cause a great deal of patient discomfort, while the chronic toxicities are often irreversible and dose-limiting. For bleomycin, the acute toxicities are mucocutaneous and pyretic, while severe nausea and vomiting represent the major acute toxicities of cisplatin therapy. Cumulative dose-related pulmonary toxicity is the most serious chronic toxicity of bleomycin. The clinical, radiographic, and pathologic presentations are nonspecific, although identification of high-risk patients may be possible with serial pulmonary function tests. Cumulative nephrotoxicity occurs with cisplatin use and its incidence and severity can be reduced by maintaining adequate hydration and diuresis during and following administration of the drug.

Aged↗

PubMedDate not supplied

Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience.

Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.

Adolescent↗

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Toward a symmetrical and an integrated framework of norms for nutrition communication in sub-Saharan Africa.

Nutrition is crucial to national development; an undernourished or a malnourished population is at risk for infectious diseases that may reduce its working and productive capacities. Sub-Saharan Africa leads the world in the proportion of its population that is chronically malnourished. This article presents a symmetrical and an integrated framework of norms for nutrition communication. It uses three nutrition communication projects in Africa to illustrate the application of those norms. Based on that review, it concludes that a community-based framework should emphasize at the outset--and throughout program implementation and evaluation--the importance of folk media (e.g., Africa's "oramedia") as both formative and summative norms for planning, implementing, and evaluating nutrition communication programs in Africa.

Africa South of the Sahara↗

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Comparison of cytokines in children with recurrent solid tumors treated with intensive chemotherapy.

PURPOSE: To compare the relative hematopoietic protective effects of recombinant human interleukin-1alpha (rhuIL-1alpha), recombinant human granulocyte macrophage colony-stimulating factor (rhuGM-CSF), and PIXY321, a genetically engineered fusion protein combining interleukin-3 and rhuGM-CSF, in children with refractory solid tumors after treatment with ifosfamide, carboplatin, and etoposide (ICE). PATIENTS AND METHODS: A total of 53 children who had not responded to at least one earlier chemotherapy regimen were enrolled on consecutive trials of ICE chemotherapy alone (n = 14) or with rhuGM-CSF (n = 8), rhuIL-1alpha (n = 10), or PIXY321 (n = 21). The relative hematopoietic effects of these three cytokines were compared retrospectively to each other and to values for patients who received ICE alone. Because one cannot assume that hematopoietic toxicity and response to a given cytokine are independent of the course of chemotherapy, the analysis was restricted to the first treatment course. RESULTS: In this retrospective comparison, 1000 microg/m2/day of rhuGM-CSF reduced the median duration of grade 4 neutropenia (<500/microL) from a median of 17 days (range 3 to 34) in children who received ICE alone to 9 days (range 5 to 11, p = 0.003); it appeared to have a beneficial effect on severe thrombocytopenia (<20,000/microL), reducing the median duration from 4.5 days with ICE alone to 3 days (p = 0.08) and the number of platelet transfusions from a median of 5.75 transfusions (range 0 to 13) to 0 in these two cohorts. No significant improvement in these measures was seen with rhuIL-1alpha or PIXY321. CONCLUSIONS: This analysis suggests that 1000 microg/m2/day of rhuGM-CSF has clinically significant effects on platelet recovery and more effectively ameliorates thrombocytopenia and neutropenia than either rhuIL-1alpha or PIXY321 in the context of ICE chemotherapy. Further dose-intensification will require a combination of cytokines; the optimal dose and combination of these agents awaits further study.

Adolescent↗

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Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

PURPOSE: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy. PATIENTS AND METHODS: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.6, 1.2, or 1.8 mg/kg) were studied. Safety, efficacy, and pharmacokinetic parameters were assessed over 24 hours at each dosage level. RESULTS: The most effective dose was 1.8 mg/kg; 60% of the patients achieved a complete or major response (< or =2 emetic episodes in 24 hours). A complete response was achieved in 3 of 9 patients (33%) who received 0.6 mg/kg, 4 of 13 (31%) patients who received 1.2 mg/kg, and 5 of 10 (50%) patients who received 1.8 mg/kg of dolasetron. Overall, dolasetron was well tolerated. Adverse events were mild and similar to those reported in adults. Peak plasma concentrations (Cmax) of dolasetron's active reduced metabolite, MDL 74,156, were dose proportional and occurred, on the average, within 1 hour of oral administration. The half-life (t1/2) in plasma was approximately 6 hours for all dose levels, and the mean clearance (CLapp) was unrelated to dose. CONCLUSIONS: Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting, particularly at the 1.8-mg/kg dose level. These results support further evaluation of oral dolasetron in larger randomized clinical trials in the pediatric cancer population.

Administration, Oral↗

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Brain metastases in pediatric Ewing sarcoma and rhabdomyosarcoma: the St. Jude Children's Research Hospital experience.

PURPOSE: Although brain metastases rarely occur in children with solid tumors, pediatric Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are among those most likely to metastasize to the brain. The authors review their institution's experience of brain metastases of ES and RMS. PATIENTS AND METHODS: The clinical characteristics, therapy, and outcome of all patients treated at St. Jude Children's Research Hospital over a 36-year period who had ES or RMS with brain metastases were reviewed. RESULTS: Of 419 patients with RMS, 10 (2.4%) had brain metastases. Of 335 patients with ES, 11 (3.3%) had brain metastases. The median age of the 21 patients was 10.4 years (range, 0.4-18.0 years) at the time of primary diagnosis. All had clinical signs of central nervous system (CNS) involvement. Outcome was dismal: The median duration of survival after diagnosis of brain metastasis was 2.7 months. The estimated survival 1 year after detection of brain involvement was 23.8%+/-8.5% (mean +/- standard error). One patient, who underwent chemotherapy, surgical resection, and radiotherapy, at the time of this writing is a long-term survivor. CONCLUSIONS: Brain metastases are rare in children with ES and RMS, but carry a grave prognosis. Because most brain metastases are accompanied by signs of neurologic involvement, routine imaging studies of asymptomatic children are not necessary. Combined-modality treatment offers the best chance of long-term survival.

Adolescent↗

PubMedDate not supplied

Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas.

PURPOSE: The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital. METHODS: The authors reviewed the records of 199 patients receiving ICR at St. Jude between June 1986 and December 31, 1994 for evidence of RTT. Their median age was 13.3 years (range 1.2-24.8); 150 patients were white and 112 were male patients. Diagnoses included osteosarcoma (n = 82), Ewing sarcoma (n = 82), rhabdomyosarcoma (n = 28), and a group of other tumors (n = 7). RESULTS: The authors estimated the proportion of patients with severe RTT during the first five cycles of ICR and within 1 year after therapy for three groups of patients receiving ifosfamide (IFOS, n = 110), ifosfamide/cisplatin (IFOS/CDDP, n = 51), and ifosfamide/carboplatin (IFOS/CARBO, n = 38). The IFOS/CDDP patients received three cycles of IFOS before receiving CDDP and received only 200 mg/m2 by cycle 5, whereas the IFOS/CARBO patients received both agents simultaneously. The authors compared the probability of severe RTT among treatment groups using a generalized linear model for the first five cycles of ICR, as well as the probability of severe RTT within 1 year after therapy among treatment groups for patients receiving all prescribed IFOS using an exact chi-square test with pairwise comparisons when the three-way P value was less than 0.10. The proportion of patients with severe RTT during the first three cycles of ICR was significantly greater in the IFOS/CARBO group than in the other two. Although the proportion of patients with severe RTT in the IFOS/CDDP group increased during cycles 4/5, the proportion of patients with severe RTT remained significantly greater in the IFOS/ CARBO group. Within 1 year after therapy, the proportion of patients with severe RTT differed among the three groups, and pairwise comparisons revealed a significant difference between the IFOS and the IFOS/CDDP group. Severe RTT developed in four IFOS/CDDP patients more than 1 year after therapy, suggesting a long-term effect of CDDP on tubular function. CONCLUSIONS: Chemotherapy regimens including IFOS/ CARBO produce severe acute RTT more frequently than regimens including IFOS or IFOS/CDDP. Patients receiving IFOS/ CDDP appear at risk for delayed RTT. Long-term follow-up of these patients is essential to assess whether the number of patients receiving IFOS/CDDP with severe RTT continues to increase over time and to evaluate the long-term significance of these abnormalities.

Adolescent↗

PubMedDate not supplied

Neonatal cancer.

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Humans↗

PubMedDate not supplied

Chemotherapy for extraocular retinoblastoma.

Because few patients with extraocular retinoblastoma are seen in the United States and Europe, it has been difficult to establish the optimal role of chemotherapy in such cases. We examined the efficacy of two chemotherapy combinations (cisplatin/etoposide and cyclophosphamide/doxorubicin) in patients with extraretinal retinoblastoma, administered prior to radiotherapy in four patients with recurrent or advanced primary disease. Responses were evaluable in three patients, each of whom was treated by both chemotherapy regimens and radiotherapy. Multimodality therapy promises to be of benefit to patients with extraocular retinoblastoma, and future studies will explore alternative chemotherapy combinations for this purpose.

Antineoplastic Combined Chemotherapy Protocols↗