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Biomedical subjects

C B Pratt

Publications and source records attributed to C B Pratt.

At least 199 records · Page 11Linked to original sources
PubMed1981

Malignant germ cell tumors in 57 children and adolescents.

Fifty-seven patients with malignant germ cell tumors (GCTs) treated at our center between 1962 and 1979 were evaluated to determine 1) the prognostic value of disease stage, tumor histology, primary site, and patient age; 2) results of therapy; and 3) patterns of metastasis. The 35 girls and 22 boys were from 1 week to 18 years old (median 5 yr). Primary sites were ovarian (20), testicular (10), sacrococcygeal (12), retroperitoneal (7), mediastinal (5), and other (3). Cox regression analysis indicated that stage was the most important prognostic variable. Extragonadal tumors were usually advanced at diagnosis, but tumor site did not have prognostic value independent of disease stage. Neither patient age nor tumor histology significantly influenced outcome. Drugs active against malignant GCTs included vincristine, cyclophosphamide, and dactinomycin in combination and vinblastine, bleomycin, and cis-platinum. Radiation alone cured nondisseminated germinomas. The most common sites of metastasis were lungs, liver, central nervous system, and bone; other sites were infrequently involved. We conclude that stage was the most important prognostic variable, extragonadal tumors were usually advanced at diagnosis, and similarities in the histogenesis, metastatic pattern, and response to therapy, regardless of primary site, justify the consideration of childhood malignant GCTs as one group.

Adolescent↗
PubMed1981

Serum pesticide levels in patients with childhood colorectal carcinoma.

From September 1974 through November 1976, 13 adolescent patients with mucin-producing colorectal adenocarcinoma were treated at a Memphis, Tennessee, pediatric oncology center. Ten of these children were from rural areas of the Mississippi Delta, areas of high pesticide use. None of them had a family history of colorectal cancer, familial polyposis, or ulcerative colitis. Levels of pesticide residues, however, were not generally higher in blood samples from patients and their families than from controls.

Adenocarcinoma↗
PubMed1981

Malignant melanoma in children and adolescents.

Thirty-one children and adolescents with malignant melanoma were treated at the Christie Hospital and Holt Radium Institute between 1945 and 1977. Locations of primary lesions included head-neck 14, trunk nine, and extremity eight. Twenty-five patients had clinically localized tumor at diagnosis, four had regional disease, and two had generalized tumor. Surgery was the primary modality of therapy. Fifteen patients survive without active disease from two years to more than 18 years, and 16 patients died of disease.

Adolescent↗
PubMed1981

Pharmacokinetics of sustained serum methotrexate concentrations secondary to gastrointestinal obstruction.

A physiological pharmacokinetic model for methotrexate was refined and used to simulate serum methotrexate concentrations after high dose (5000 mg/m2) intravenous infusions with fixed normal values for all model parameters except the GI transit rate. There was good agreement between simulated and measured values when model simulations with the normal GI transit rate were compared to values measured following 109 doses administered to 27 patients with normal GI function. When model simulations were performed using GI transit rates representing 75, 50 and 10% of normal, there was a marked prolongation of the terminal serum methotrexate half-life, which was directly related to the reduction in the transit rate. When simulations were performed with GI transit reduced by 50%, the maximum amount of methotrexate in the GI lumen was 25% higher and occurred 4 hr later. Model simulations of serum methotrexate concentrations, using a GI transit rate reduced by 50%, were also in good agreement with serum concentrations measured in two patients with partial GI obstruction. These data establish a pharmacokinetic basis for previous clinical observations indicating sustained serum methotrexate concentrations in patients with GI obstructions and exemplify the utility of physiological pharmacokinetic models in assessing the potential effects of clinical variables on drug disposition.

Half-Life↗
PubMed1981

Cisplatin disposition in children and adolescents with cancer.

The disposition of cisplatin was evaluated in 28 children and adolescents with cancer, as part of a phase II clinical trial. Patients received either 30 mg/m2 (11) or 90 mg/m2 (17) of cisplatin as a 6-h IV infusion. Serum samples and divided urine collections were obtained over 48 h following completion of the cisplatin infusion, and were assayed in duplicate for total platinum by atomic absorption spectrophotometry. Serum samples obtained up to 4 h after three cisplatin infusions were assayed for parent (free) cisplatin following ultrafiltration. The mean (+/- SE) elimination half-life of free cisplatin in serum was 1.3 (+/- 0.4) h. Serial serum concentrations of total platinum following 90 mg/m2 dosages were adequately described by a biexponential equation. The mean (+/- SE) serum T 1/2 alpha of total platinum was 0.42 (+/- 0.10) h and the mean (+/- SE) T 1/2 beta was 44.43 (+/- 8.24) h. The intercompartment distribution rate constants of a two-compartment kinetic model indicate extensive tissue accumulation of total platinum, with a rate of transport into tissue compartments (K12) that is about six times the rate of transport out of tissues (K21). The mean (+/- SE) renal clearance of total platinum from 0-3 h was 37.36 (+/- 11.96) ml/min/m2 and 35.8 (+/- 13.6) ml/min/m2 for the 30 mg/m2 and 90 mg/m2 groups, respectively. This value decreased to 3.25 (+/- 0.94) and 2.16 (+/- 0.4) ml/min/m2 for the two groups by the 6-12 h interval, and remained between 1 and 3 ml/min/m2 for the duration of the observation period. The ratio of total platinum clearance to creatinine clearance decreased significantly (P less than 0.05) beginning 3 h post-infusion. The change in renal clearance of total platinum is apparently a function of two independent first-order processes for renal clearance of parent drug and cisplatin metabolites.

Adolescent↗
PubMed1981

Selected applications of methotrexate alone and in combination in osteosarcoma.

Review of the reported use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CF) for treatment of primary and metastatic osteosarcoma indicates the rarity of responses in clinical situations other than treatment of the primary tumor or isolated pulmonary metastases with doses of 7.5 g/m2 or greater delivered on a weekly basis for 4 to 6 weeks. Adjuvant chemotherapy using HDMTX-CF at triweekly intervals has led to 2-year disease-free survival rates that are inferior to those obtained with combinations of agents including HDMTX-CF Adriamycin (Adria), with or without vincristine, cyclophosphamide, phenylalanine mustard, bleomycin, and dactinomycin. We concluded that although HDMTX-CF has a role in the treatment of primary and metastatic osteosarcoma, its use in combination with other active agents offers greater potential advantage to affected patients.

Antineoplastic Agents↗
PubMed1981

Treatment of childhood rhabdomyosarcoma at St. Jude Children's Research Hospital, 1962--78.

Between March 1962 and December 1978, 153 children with rhabdomyosarcoma (RMS) received treatment at St. Jude Children's Research Hospital. As of January 1979, 62 of these patients were still alive. Between 1962 and 1968, 20 patients were not treated by protocol, and, between 1968 and 1979, another 13 have been registered as "nonprotocol"; 6 of these 33 patients survive. Since 1968, 120 patients received treatment by 3 stage-related, multiple-modality programs. In the first protocol, chemotherapy consisted of vincristine, cyclophosphamide, and dactinomycin; 14 of 34 patients have survived after 6 to more than 10 years. In the second treatment program, which used adriamycin in addition to the 3 drugs cited above, 20 of 56 subjects remain free of disease after more than 2 to 5.5 years; toxicity of the multiple agents given in combination with radiotherapy proved intolerable and led to a modified 4-agent protocol for patients admitted since early 1977. Of 30 in this latter group, 22 are alive. Forty of 44 patients who remained free of RMS for more than 2 years continue to survive.

Adolescent↗
PubMed1980

Breast metastases in children with rhabdomyosarcoma.

Of 108 consecutively diagnosed patients with rhabdomyosarcoma, seven subsequently developed clinically evident metastatic tumors of the breast. These patients were unusual in that all had primary tumors located on an extremity or the buttock, and six of the seven tumors had alveolar histology. Sex distribution and age of the patients indicated that the physiologic state of the breast was an important determining factor in the development of such metastases.

Adolescent↗
PubMed1980

Osteosarcoma, fibrous dysplasia, and a chromosomal abnormality in a 3-year-old child.

Osteosarcoma is a type of malignant bone tumor that is rare among children less than five years old. This report describes a 3-year-old boy with osteosarcoma of the right proximal femur and polyostotic fibrous dysplasia of the right femur and tibia. After hemipelvectomy, histologic examination of the amputated limb disclosed that the osteosarcoma had developed in a focus of fibrous dysplasia. Cytogenetic analysis of the patient's blood lymphocytes revealed a 4q-/7p + translocation in all cells. The patient's mother had an identical translocation but did not have a history of osteosarcoma or evidence of fibrous dysplasia. The chromosomal abnormality and the developmental osseous disorder may have predisposed this patient to developing osteosarcoma at an exceptionally young age.

Child, Preschool↗
PubMed1980

Combined VM-26 and cytosine arabinoside in treatment of refractory childhood lymphocytic leukemia.

On the basis of previous findings at this institution, VM-26 and Cytosine Arabinoside (ara-C) were used in combination to treat 33 children with refractory acute lymphocytic leukemia (ALL). Chemotherapy was given by vein twice a week for four weeks at dosage of 300 mg/m2 for ara-C and 50, 75, 110, 165, or 200 mg/m2 for VM-26. Ten marrow remissions (nine complete and one partial) were induced, with hypotension (2/33) and bone marrow hypoplasia (20/33) the most significant side effects observed. Therapeutic responses were obtained with each dosage of VM-26 except 75 mg/m2; myelosuppression developed at all dosages, being most prolonged at 200 mg/m2. Ten of the 23 non-responders did not complete their planned courses of therapy. The significance of this information is that combinations of VM-26 and ara-C were effective in patients who were either in late stages of their leukemia or had never achieved an initial remission. All had been previously treated with prednisone, vincristine, daunomycin and L-asparaginase. In addition, seven of the 10 responders had previously received ara-C in other drug combinations. The use of VM-26 and ara-C in combination may be warranted for newly diagnosed patients who are at high risk for treatment failure with first-line drugs.

Adolescent↗
PubMed1980

Retroperitoneal rhabdomyosarcoma in children. Results of multimodality therapy.

The clinical course of 18 consecutive children treated for primary retroperitoneal rhabdomyosarcoma was reviewed. At diagnosis, 8 patients had regional unresected tumor and 10 patients had disseminated tumor, including 3 patients with documented bone marrow infiltration by tumor. Following combined modality therapy, 14 of 18 patients achieved a greater than 50% tumor response (11 complete and 3 partial responses); 4 patients failed to respond and died of progressive disease within eight months of diagnosis. Among the 14 patients responding, 7 patients had subsequent reextension of active tumor three to 16 months (median, 9 months) following the onset of therapy. Three of the 7 remaining patients died of treatment complications, 2 of intestinal obstruction and 1 of disseminated histoplasmosis, within the first year of therapy and at post-mortem examination had no demonstrable tumor. Four patients are alive and free of active tumor for 10+, 10+, 32+ and 33+ months from diagnosis. Treatment complications have included hematopoietic depression, mucositis, enteritis, intestinal obstruction, excessive weight loss, malnutrition, and life-threatening infection. These results illustrate limitations in current combined modality therapy of retroperitoneal rhabdomyosarcoma and the necessity for future treatment modifications to both reduce morbidity and to improve survival.

Adolescent↗
PubMed1980

Phase I clinical and pharmacokinetic study of 4'-(9-acridinylamino)-methanesulfon-m-anisidide in children with cancer.

Forty-one pediatric patients with advanced cancer (24 with acute leukemia and 17 with diverse solid tumors) received 74 courses of therapy with a new chemotherapeutic agent, 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA: NSC 249992). Treatments were given by slow i.v. injection daily for five days every two to three weeks. In patients with leukemia: (a) dosages were escalated from 1.3 to 150 mg/sq m/day; (b) toxicity in the form of stomatitis, vomiting, and phlebitis occurred at dosage levels of 125 to 150 mg/sq m/day; and (c) oncolytic effects were observed in 13 of 24 patients. In patients with solid tumors: (a) dosages were escalated from 5 to 50 mg/sq m/day; (b) toxicity (stomatitis, myelosuppression, and phlebitis) occurred at the dosage level of 50 mg/sq m/day; and (c) no oncolytic responses were noted. Serum concentrations of total and free AMSA were assayed by a fluorescence technique and declined in a biphasic manner with free AMSA declining more rapidly than total AMSA. Dosages of greater than 100 mg/sq m/day were required to maintain serum concentrations of total and free AMSA greater than 0.2 microM for the entire five-day schedule. The results suggest that maximum tolerated dosages of AMSA may differ in children with leukemia and solid tumors; however, hematopoietic toxicity could not be fully evaluated in the patients with leukemia. AMSA has clear antileukemic activity that warrants future Phase II trials.

Adolescent↗
PubMed1980

High-dose methotrexate used alone and in combination for measurable primary or metastatic osteosarcoma.

High-dose methotrexate with leucovorin rescue was used alone or in combination with Adriamycin and cyclophosphamide for the treatment of 27 osteosarcoma patients with measurable indicators of disease. Three patients developed complete responses of measurable lesions, two had partial responses, two had static disease, one had symptomatic improvement, and one had return to normal of physical findings following treatment of a flat bone primary osteosarcoma. While the doses and frequency of administration of high-dose methotrexate differed from those used by previous investigators, these results suggest that aggressive treatment with high-dose methotrexate must be attempted to further evaluate its efficacy as single-agent therapy for osteosarcoma patients not eligible for adjuvant chemotherapy trials.

Antineoplastic Agents↗
PubMed1979

Serum levels of methotrexate by the ligand-binding assay after "high-dose" therapy for osteosarcoma.

The method of Arons et al. (Cancer Res. 35:2033-2038, 1975) for assaying methotrexate (MTX) was used to monitor serum levels of the drug attained in 18 patients with osteosarcomas. The patients received either 100 mg or 200 mg of MTX/kg via a 6-hour infusion. With one fatal exception, unacceptable toxicity to MTX was prevented by leucovorin. Serum levels of the drug were assayed routinely at 6, 12, and 18 hours after termination of the infusion. Although significantly higher serum levels of MTX were observed at 6 hours after the infusion of 200 mg MTX/kg than after 100 mg/kg, the variation in rate of clearance of individual patients masked any subsequent dosage-related differences. The mean half-time for clearance of MTX was similar irrespective of the dosage of MTX and was 2.91 +/- 1.51 hr for 53 treatments. The single incidence of toxicity, requiring hospitalization, was accompanied with markedly higher serum levels of MTX at 18 hours, but not at either 6 or 12 hours after termination of the drug infusion, and by a slightly slower rate of clearance, 6.2 hours. Certain minor adaptations were incorporated in the original assay to simplify the analysis of data.

Drug Therapy, Combination↗