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Biomedical subjects

C B Pratt

Publications and source records attributed to C B Pratt.

At least 127 records · Page 7Linked to original sources
PubMed1991

An exploratory study of environmental and medical factors potentially related to childhood cancer.

To determine whether a general-purpose epidemiologic questionnaire can be used in childhood cancer hospitals to identify associations between environmental factors and the major types of childhood cancer, we report the results of the analysis of the data obtained from such a questionnaire. On admission to St. Jude Children's Research Hospital in Memphis, Tennessee, between 1979 and 1986 a questionnaire was administered to 1,270 mothers of patients diagnosed with childhood cancer. Approximately one-half of the children had acute leukemias (n = 629); the remainder had lymphomas (n = 237) or solid tumors (n = 404). Responses to questions regarding the patients' and parents' environmental and medical histories were compared across nine diagnostic categories. Only 5 of 232 variables remained nominally statistically significant (P less than 0.05) after adjusting for confounding by patient or maternal age, year of birth or diagnosis, patient's race, and social class. The variables identified were length of time the patient was breast-fed (chi 2 = 16.1, P = 0.04); having a garden with fertilizers, herbicides, and pesticides (chi 2 = 17.2, P = 0.03); maternal use of sex hormones during the year before the patient's birth (chi 2 = 18.2, P = 0.02); maternal cigarette consumption (chi 2 = 18.0, P = 0.02); and patient contact with persons with cancer (chi 2 = 20.7, P = 0.01). Despite the large number of patients studied, we identified fewer significant variables than would be expected, on the average, under the null hypothesis. We conclude that the data obtained from a general-purpose epidemiologic questionnaire do not provide a useful overview of the association between exposure to environmental factors and several types of childhood cancer.

Breast Feeding↗
PubMed1991

Concept of maximum tolerated systemic exposure and its application to phase I-II studies of anticancer drugs.

The traditional approach to conducting Phase I studies of anticancer drugs is to select a starting dosage for humans based on preclinical data (e.g., mg equivalent of 1/10 LD10 in mice), then empirically escalate dosages in cohorts of patients until the maximum tolerated dosage (MTD) is established. More recently, NCl and EORTC investigators have advocated the use of pharmacokinetic data from preclinical studies to facilitate more rapid dose escalation (e.g., double the dose until the area under the concentration-time curve [AUC] in humans equals the AUC in mice at the LD10). The present paper describes a strategy which builds on the above approach, by extending the application of pharmacokinetic principles to systematically escalate systemic exposure (AUC) instead of dosage in Phase I trials. Human trials are initiated at whatever patient-specific dosage is required to achieve an AUC equal to 1/10 the AUC in mice at the LD10, such that three patients at the first treatment level might receive three different dosages. If no dose-limiting toxicity is observed, the next cohort of patients receives whatever dosage is required to achieve 2 x AUC of the first dosage level, with AUC escalation continuing until the maximum tolerate systemic exposure (MTSE) is reached. By escalating systemic exposure instead of dosage, one adjusts for interpatient pharmacokinetic variability. This strategy will permit more rapid and precise dosage escalations and, more importantly, it should more precisely establish the maximum level of treatment intensity for future Phase II trials.

Antineoplastic Agents↗
PubMed1991

The conduct of phase I-II clinical trials in children with cancer.

Phase I Clinical Trials in children with cancer are carried out with therapeutic intent, so as to define antileukemic/antitumor activity, dose-limiting toxicity, maximum tolerated dosage, and pharmacokinetics. These studies define a dosage of an agent or combination that may be used in a larger study of pediatric patients with leukemias or malignant solid tumors. The content of phase I and II protocols is outlined, with a brief discussion of the ethics of performance of phase I trials in children.

Child↗
PubMed1991

Phase I study of flavone acetic acid (NSC 347512, LM975) in patients with pediatric malignant solid tumors.

To evaluate the anticancer agent flavone acetic acid (FAA), we conducted a Phase I trial involving 17 pediatric patients with various malignant solid tumors. Dosages investigated included 5,120 and 6,144 mg/m2 given as 3-hour intravenous infusions; and 10,000, 12,500, 15,000, and 17,500 mg/m2 delivered in a 24-hour constant infusion with alkalinization. Grade 2 or worse toxicity was minimal, with 2 patients having nausea/vomiting, 2 having diarrhea, 1 becoming hypertensive, 1 becoming hypotensive, and 2 having myalgia. Three patients who received a 17,500 mg/m2 dose had no toxicity. Disease was stabilized for a brief period in 2 patients--1 with brain stem glioma and 1 with astrocytoma. The FAA pharmacokinetics varied with an average (SD) terminal half-life of 27.9 hr (18.7), clearance of 2.04 L/hr/m2 (0.37), and steady-state volume of 19.9 L/m2 (10.6). This study was discontinued because FAA caused no significant toxicity or therapeutic responses at doses 2.5 gm/m2 greater than had been tolerated by adults.

Adolescent↗
PubMed1991

Therapeutic effects and pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in childhood cancer patients receiving myelosuppressive chemotherapy.

Twenty-five children with refractory solid tumors were given recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in escalated doses of 60 to 1,500 micrograms/m2 as 2-hour intravenous infusions, beginning 24 hours after myelosuppressive treatment with cisplatin and etoposide. Tolerance to rhGM-CSF was exceptional even at dose levels that exceeded the maximum-tolerated dosage (MTD) reported for adults. The agent produced dose-related increases in platelet and neutrophil counts, resulting in significantly shorter durations of severe neutropenia and thrombocytopenia (P less than .01 for each analysis). At the higher dosages (greater than or equal to 750 micrograms/m2), treatment with rhGM-CSF reduced the median number of days of antibiotic therapy for fever and neutropenia by approximately one half. We conclude that rhGM-CSF is well tolerated by leukopenic children in doses as high as 1,500 micrograms/m2. An MTD was not reached in this study. The ability of the growth factor to reduce severe neutropenia and thrombocytopenia suggests it will have an important role in the management of childhood solid tumors.

Adolescent↗
PubMed1991

Ifosfamide, Fanconi's syndrome, and rickets.

Three of 218 children treated with ifosfamide plus the uroprotectant mesna, in single- or combination-agent protocols, have developed Fanconi's renal syndrome, all of whom were in a subgroup of 86 children who had also received cisplatin or carboplatin therapy. Patients receiving ifosfamide who have received prior cisplatin (or carboplatin) are at significantly higher risk of developing Fanconi's syndrome than are those who have received no prior nephrotoxic therapy (P = .04). The role of prior nephrotoxic therapy, including cisplatin and its derivatives, and the total dose of ifosfamide should be considered in the assessment of this rare but serious and apparently irreversible side effect.

Adolescent↗
PubMed1991

Secondary non-Hodgkin's lymphoma after treatment for childhood cancer.

To determine the risk and pertinent features of non-Hodgkin's lymphoma (NHL) as a second malignancy, medical records were searched of 5484 consecutive children treated for various malignancies at a single institution during a 27 year period. Of these, three have developed secondary NHL. The probability of secondary NHL in this cohort at 5 and 10 years after the diagnosis of the first malignancy was 0.05% (95% confidence interval, 0.01%, 0.2%) and at 15 years 0.16% (0.04%, 0.63%). With 30710 person-years observed, the risk in this cohort was 9.8 per 100,000 person-years. A literature search disclosed variously detailed descriptions of 21 cases of secondary NHL in patients whose primary malignancy had been diagnosed when they were less than 20 years old. Of 18 cases with documented secondary NHL histology, the most common subtypes were large cell (n = 7) and small non-cleaved cell (n = 6); mixed histology was found in three and lymphoblastic in two cases. Twenty-three of 24 children with secondary NHL had initial lymphohematopoietic neoplasms: Hodgkin's disease (n = 18), acute lymphoblastic leukemia (n = 4) and acute myelogenous leukemia (n = 1); the remaining child had astrocytoma. Of 18 patients (including three cases from this institution) with known outcome, only four were reported to be alive at 5+, 6+, 12+ and 96+ months, respectively. Secondary NHL occurs most often after therapy for Hodgkin's disease and confers a dismal prognosis.

Adolescent↗
PubMed1990

Myeloid neoplasia in children treated for solid tumours.

Therapy-related myeloid neoplasia developed 14 to 189 months after diagnosis of the primary malignancy in 12 out of 3365 children treated for malignant solid tumours; 6 of the 12 were in their first complete remission. The 10-year cumulative incidence of myeloid neoplasia was 1.3% (95% Cl 0.5-3.6) for the 447 patients with Hodgkin's disease, 1.3% (0.4-4.3) for the 420 with non-Hodgkin lymphoma, and 1.2% (0.3-5.2) for the 440 with neuroblastoma. This complication appeared in 1 of 180 children with brain tumours and in none of the 1878 with other malignancies. Risk of therapy-related myeloid neoplasia in patients with Hodgkin's disease was associated with recurrence of the primary malignancy, a combination of radiotherapy and chemotherapy with alkylating agents, and age greater than or equal to 12 years at diagnosis of Hodgkin's disease. Of the 8 patients who underwent chromosomal analysis of neoplastic myeloid cells, 2 showed complete loss of chromosome 7 and 4 showed t(9;11) or t(8;21) with or without del(16)(q22). The 2 patients who had received an epipodophyllotoxin had an 11q23 abnormality. The risk of therapy-related myeloid neoplasia is low in children with malignant solid tumours.

Adolescent↗
PubMed1990

Sarcomas (other than Ewing's) of flat bones in children and adolescents. A clinicopathologic study.

The clinicopathologic features and response to therapy of 28 patients with non-Ewing's flat bone sarcoma treated at St. Jude Children's Research Hospital, Memphis, Tennessee, over a 25-year period were reviewed. Twenty-two patients had osteosarcoma, four malignant fibrous histiocytoma, one chondrosarcoma, and one fibrosarcoma. Ages at diagnosis ranged from 3 to 24 years (median, 15 years). Primary sites were craniofacial bones in ten patients, pelvis eight, scapula four, ribs two, metatarsal bones two, clavicle one, and vertebra one. All primary tumors were associated with soft tissue extension; none of the patients had metastatic disease at presentation. Six cases represented second malignancies that arose 5 to 16 years after irradiation for an unrelated tumor. Complete excision was possible in ten patients, eight of whom received postoperative chemotherapy. Five of these patients remain free of disease 1.8+ to 13+ years (median, 8.1 years) from diagnosis. Prolonged remissions after adjuvant chemotherapy were achieved in only two of 18 patients after incomplete surgical resection or biopsy. The median survival time in this group was 1 year (range, 0.2-7.7+ years). The remaining 16 patients had progressive local disease, but only two developed concurrent metastases. Thus, complete surgical resection appears to maximize disease-free survival in patients with non-Ewing's flat bone sarcoma. For the large percentage of patients in whom total resection is not possible, because of soft tissue extension and local invasion of bulky tumors, preoperative chemotherapy may increase the likelihood of complete excision and improve long-term survival.

Adolescent↗
PubMed1990

Adjuvant chemotherapy for osteosarcoma of the extremity. Long-term results of two consecutive prospective protocol studies.

Seventy-six patients with classic high-grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high-dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high-dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long-term disease-free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

Adolescent↗
PubMed1990

Skeletal scintigraphy in patients with bilateral retinoblastoma.

One hundred-seventeen radionuclide bone scans were performed on 46 patients with bilateral retinoblastoma between diagnosis and 19 years from diagnosis for the purpose of detecting skeletal metastases or other malignant neoplasms of bone that might develop in this group of patients at high risk for a second malignancy. Only one child, who had been symptomatic for 1.5 years, had a scan positive for metastasis at diagnosis. Scans in three additional children became positive (in one after the development of metastatic disease involving bone and soft tissue but not bone marrow 2 years after the diagnosis of retinoblastoma, and in two others after the development of osteosarcoma at 10.5 and 16 years from the diagnosis of retinoblastoma). Our data indicate that bone scans should not remain as part of the initial staging of patients with bilateral retinoblastoma unless there is clinical or pathologic evidence of extraocular disease at diagnosis. The performance of skeletal scintigraphy also is not warranted, with the expectation of diagnosing a second malignant neoplasm (namely osteosarcoma).

Bone Neoplasms↗
PubMed1990

False-positive ketone tests: a bedside measure of urinary mesna.

The sulfhydryl mesna is increasingly used to protect the bladder and kidney from effects of chemotherapy with ifosfamide and cyclophosphamide. Mesna reacts with reagents on urinary test strips designed to detect ketones. Test-strip results were correlated to sulfhydryl concentrations in 931 urine specimens obtained after infusions of mesna. These data may be used to estimate urinary mesna concentrations at the bedside or to test compliance in outpatients given oral mesna therapy.

Adolescent↗
PubMed1990

Malignant melanoma in children: its management and prognosis.

Malignant melanoma is rare in children, representing 1% to 3% of all pediatric malignancies. Thirty-three children with malignant melanoma were treated at St Jude Children's Research Hospital from 1967 to 1988. Their ages ranged from 1 day to 20 years (median, 12 years); 23 were boys and 10 were girls; and 5 of the 33 (15%) were black. Four of the 33 children had been treated for a previous malignancy. In 3, melanoma arose within a bathing trunk nevus. The extremity was the most common site (13), followed by the trunk (9), head and neck (7), and perineum (1). In 3 patients the primary site could not be determined. Upon initial presentation to St Jude Hospital, 17 patients had localized disease (stage I), 10 had regional node involvement (stage II), and the remaining 6 patients had disseminated disease (stage III). Using both Clark's level and Breslow's thickness as indicators, the incidence, initial stage, prognosis, and survival were compared. By Clark's level, 7 patients, (6 of whom were stage I) were level II or III, and 22 patients were level IV or V. Though 16 of 22 level IV and V patients were initially stage I, 10 patients eventually developed progressive disease. Similar observations were noted when using Breslow's thickness to evaluate the primary. In 5 of 27 evaluable patients, Breslow's depth of invasion was less than 1.5 mm. All 5 of these patients were diagnosed with stage I disease and have not shown progressive disease.

Adolescent↗
PubMed1990

Ifosfamide neurotoxicity is related to previous cisplatin treatment for pediatric solid tumors.

Neurotoxicity developed in 22 of 97 children and adolescents with malignant solid tumors treated within a phase II ifosfamide protocol. The occurrence of neurotoxicity was related to previous cumulative dosages of cisplatin. One third of the patients who had received more than 600 mg/m2 of cisplatin developed this complication. The relative risk increased 3.2-fold with previous cisplatin dosages above 301 to 600 mg/m2, and 4.1-fold with dosages of 601 to 1,340 mg/m2. The increased risk of neurotoxicity in patients who had received more than 600 mg/m2 of cisplatin may be related to either a decreased clearance of ifosfamide itself or of the drug's active metabolites.

Adolescent↗