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Biomedical subjects

F A Hayes

Publications and source records attributed to F A Hayes.

At least 73 records · Page 4Linked to original sources
PubMed1985

Chromosome 1 abnormalities: a common feature of pediatric solid tumors.

Abnormalities of chromosome 1 were found in 32 of 46 pediatric solid tumors including Ewing's sarcoma, Wilms' tumor, rhabdomyosarcoma, primitive neuroectodermal tumor, and hepatoblastoma. Trisomy of 1q was the most common abnormality, and breakpoints were most frequent in the region 1cen to 1p22. Abnormalities of chromosome 1 are not specific to any type of tumor. However, their frequent occurrence indicates that they may endow a clonal advantage in the development of cancer.

Aneuploidy↗
PubMed1985

Allergic reactions to teniposide in patients with neuroblastoma and lymphoid malignancies.

Acute allergic reactions have been reported in 1%-5% of patients receiving teniposide. In a patient population of 82 children with leukemia and lymphoma, we observed only two acute reactions during the infusion of 1707 doses of teniposide. In contrast, 14 of 105 children with neuroblastoma developed acute allergic reactions during the infusion of 665 doses of teniposide. Four rechallenge doses of the drug were given to patients with neuroblastoma after premedication with antiallergic agents. All four doses resulted in repeat reactions. Our data suggest that children with neuroblastoma have a significantly higher incidence of acute reactions to teniposide than patients with other malignancies (P = 0.008), and that these reactions cannot be prevented by premedication with antiallergic drugs.

Child↗
PubMed1984

Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma.

We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with 2 of 25 (P = 0.003). Of 17 evaluable patients with unresectable hyperdiploid tumors, 15 had complete responses and two had partial responses to cyclophosphamide and doxorubicin; six others with diploid tumors did not respond (P = 0.00001). We also found that each of the four infants with Evans' Stage IV-S neuroblastoma, an unusual form of disseminated neuroblastoma with a relatively good prognosis, had hyperdiploid tumor cells of clonal origin. We conclude that in neuroblastoma of infants, hyperdiploidy of tumor cells is associated with a better response to chemotherapy than is diploidy.

Cyclophosphamide↗
PubMed1984

Chemotherapy as an alternative to laminectomy and radiation in the management of epidural tumor.

Nine children with neuroblastoma and five with Ewing sarcoma were found at diagnosis to have epidural extension of tumor. Five children underwent laminectomy prior to referral, with good neurologic recovery in only one. Management in the other nine children did not include laminectomy. All 14 patients were given chemotherapy without radiotherapy. Rapid regression of tumor with neurologic recovery occurred in response to chemotherapy in all patients with neurologic deficits. The responses observed in these children indicate that for chemotherapy-sensitive tumors, effective chemotherapy is a feasible alternative to laminectomy and radiation therapy in the management of epidural disease.

Adolescent↗
PubMed1984

Malignant melanoma in childhood: clinical course and response to chemotherapy.

Malignant melanoma is uncommon in patients less than 20 years of age, and little is known about the response to chemotherapy in this age group. We report here a series of 18 children, of whom ten with metastatic disease were treated with cyclophosphamide, vincristine, and dactinomycin. Only two of nine evaluable patients failed to show an objective response to therapy. Five of ten patients treated are alive and free of tumor 12 to 80 months from the start of chemotherapy. Three have been in remission for more than five years. Results suggest that melanoma in this age group may be more responsive to chemotherapy than melanoma in adult patients and that a trial of this therapy in a larger number of children with evaluable disease is warranted.

Adolescent↗
PubMed1984

Pharmacokinetics of etoposide (VP16) in children and adolescents with refractory solid tumors.

The clinical pharmacokinetics of etoposide were studied in eight pediatric patients with refractory solid tumors. The alpha-phase half-life, beta-phase half-life, volume of distribution, and elimination rate constant averaged 0.82 hr, 6.5 hr, 4.0 liters/sq m, and 0.25 hr-1, respectively. Noncompartmental parameters such as systemic clearance, mean residence time, and volume of distribution at steady-state averaged 20.9 ml/min/sq m, 7.8 hr, and 7.2 liters/sq m, respectively. A significant relationship between serum glutamic pyruvic transaminase and systemic clearance was observed, with patients having elevated serum glutamic pyruvic transaminase showing slower systemic clearance of etoposide. Systemic clearance, mean residence time, and beta-phase half-life of etoposide were significantly lower in those patients who had received cisplatin prior to their Phase II etoposide trial. The average pharmacokinetic values derived from these eight pediatric patients with solid tumors did not differ significantly from those previously reported in children with leukemia administered similar dosages and in adults given radioactively labeled etoposide.

Adolescent↗
PubMed1983

Surgicopathologic staging of neuroblastoma: prognostic significance of regional lymph node metastases.

Of 254 children with neuroblastoma treated at St. Jude Children's Research Hospital, 102 (40%) had clinically localized tumors. Using a surgicopathologic staging system, 66 of these 102 children had localized tumor and 36 had tumor dissemination to regional lymph nodes. Survival of these two groups has been markedly different; 57 of 66 (87%) with localized tumor survive, compared with 11 of 35 (33%) with node dissemination, five of whom are less than two years from diagnosis. Our data indicate that the prognosis for children with neuroblastoma metastatic only to regional lymph nodes is no different from that of patients of similar age with widely disseminated tumor.

Age Factors↗
PubMed1983

The response of Ewing's sarcoma to sequential cyclophosphamide and adriamycin induction therapy.

Twenty-four consecutive patients with Ewing's sarcoma were treated in a protocol designed to deliver induction chemotherapy with postinduction surgical-pathologic evaluation of the primary tumor site. This was followed by delayed radiotherapy, the dose and port of which was dependent on the response to induction chemotherapy. All patients received 5 courses of sequential cyclophosphamide and adriamycin during the 3-mo induction period. Nineteen of 23 evaluable patients had no gross residual tumor following this therapy. Of the remaining 4, 2 had complete surgical excision of residual gross disease. Of the 22 patients who were free of gross tumor following induction chemotherapy and surgery, 5 received no radiotherapy, 16 received moderate-dose limited port radiotherapy (3000-3500 R), and 1 received high-dose limited port radiotherapy (5000 R). All 14 patients with localized disease attained remission and are surviving 9-41+ mo (median 21+) with 2 local recurrences occurring after 10 and 33 mo of remission. Of the 10 patients presenting with metastatic disease, 8 attained complete remission with 4 of the 8 remaining disease-free 12-34+ mo from diagnosis. This study indicates that Ewing's sarcoma is very sensitive to moderate-dose 2 drug chemotherapy of low toxicity and that it is possible to delay radiotherapy and any extensive surgical procedure until remission is induced.

Adolescent↗
PubMed1983

Neuroblastoma.

Explore the source record for details and available documents.

Child↗
PubMed1982

Metastatic epidural tumors in children.

Spinal cord compression is a rare but serious complication of malignant diseases in children. Epidural cord compression was noted in 81 patients within the past 17 years at this center. The complication developed at different times during the course of the primary disease. For 29 of our patients, cord dysfunction was one of the initial signs of cancer--Ewing sarcoma, neuroblastoma, Hodgkin disease, and malignant lymphoma. By contrast, for most of the patients with osteosarcoma and rhabdomyosarcoma, it appeared later in their clinical course. The treatment outcome of patients who were paraplegia with complete loss of sensory function for greater than or equal to 48 hours was poor. Only four of 22 in this group became ambulatory. Ten patients with osteosarcoma did not undergo laminectomies because they all had multiple metastases and terminal disease. Paraplegia developed in all ten. There was no difference in ambulatory rates among other patients, with or without laminectomies.

Child↗
PubMed1982

Pharmacokinetic modeling of cisplatin disposition in children and adolescents with cancer.

A flow-limited physiologic pharmacokinetic model using volume terms, flow rates, distribution ratios, metabolic rate constants, and clearance terms restricted to physiologic or measured values was used to simulate the disposition of cisplatin in children and adolescents. Physiologic model simulations of parent cisplatin and total platinum serum concentrations were not statistically different from concentrations of these platinum species measured in 14 patients. A simplified first-order multicompartment operational model was also developed, and produced comparable simulations of parent cisplatin disposition but less accurate simulations of total platinum serum concentrations. These data provide further clarification of cisplatin disposition in humans and provide the basis for previously observed changes in the renal clearance of total platinum.

Adolescent↗
PubMed1981

Sequential cyclophosphamide and doxorubicin for induction of complete remission in children with disseminated neuroblastoma.

When 70 children with disseminated neuroblastoma were treated for 4 months with a course of cyclophosphamide and doxorubicin (Adriamycin) 35 (52%) of 68 assessable patients achieved complete remissions, 13 had partial responses, and 20 had either less than a 50% regression of tumor or evidence of tumor progression. Of the 35 children with complete responses, three received local irradiation, but for the remainder, chemotherapy alone provided rapid control of tumor growth. Drug-induced toxicity caused the hospitalization of four of 17 infants and five of 52 older children, but was related to only two of the eight deaths that occurred during treatment. Infants less than 1 year of age were more likely to achieve a complete remission than were older children. That 52% of these patients achieved complete remissions represents a marked improvement over the 22% response rate for patients seen between 1962 and 1974. Of 35 patients with complete responses, 15 have survived, contrasted with only four of 33 patients achieving less than a complete response. Median survival for patients achieving a partial response was 14.4 months, compared to 8.4 months for patients not achieving a response. A kinetically based sequence of chemotherapy seems to produce a high rate of complete remissions in children with disseminated neuroblastoma. To consolidate this gain into curative treatment will require a continuation therapy to prevent the emergence of drug-resistant disease.

Adolescent↗
PubMed1981

Clinical evaluation of sequentially scheduled cisplatin and VM26 in neuroblastoma: response and toxicity.

Cis-dichlorodiammineplatinum (CDDP) and VM26, both of which have been proven efficient in treating neuroblastoma, were combined in a sequential schedule and administered to 22 children with disseminated neuroblastomas resistant to treatment with cyclophosphamide and doxorubicin (Adriamycin). During this same study, 14 children were prospectively evaluated for the effect of CDDP on magnesium metabolism and the effect of the induced hypomagnesemia on parathyroid function. Complete or partial tumor responses were achieved in six and nine cases. Respectively and were of prolonged duration (longer than six months) in eight of the 15 responding. It was also shown that CDDP-induced hypomagnesemia is the result of excessive renal loss and is severe enough to interfere with the normal parathormone response to hypocalcemia.

Bone Marrow↗
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

Cytogenetic features of human neuroblastomas and cell lines.

We reviewed the banded karyotypes of 24 human neuroblastomas and cell lines to identify any consistent chromosomal abnormalities. Six of the 10 primary tumors and one of the 14 cell lines were studied at this institution. Of the 24 neuroblastomas karyotyped, 20 were near-diploid, one was near-triploid, and 3 were near-tetraploid. One primary tumor had a diploid karyotype without numerical or structural rearrangements. The 20 cases with a karyotype in the diploid range were statistically analyzed for gain or loss of while chromosomes and for structural abnormalities of each chromosome arm. The short arm of chromosome 1 was preferentially involved in structural rearrangements, occurring in 14 cases (p less than 0.01). In 11 of these cases, the abnormality of chromosome 1 included deletion of bands 1p32 leads to 1pter, rendering the cells monosomic for this genetic material. Of the remaining three cases, one involved a reciprocal translocation of chromosomes 1p and 12q, another had insertion of genetic material at band 1p13, and the third had an extra dark band at 1p36. No other numerical or structural abnormalities occurred with sufficient frequency to reach statistical significance (p greater than 0.20). Six of the primary tumors or cell lines in the diploid range had double minute chromatin bodies, four cell lines had homogeneously staining regions, and two cell lines had either double minute chromatin bodies or homogeneously staining regions in subpopulations of cells. Hence, partial monosomy for the short arm of chromosome 1 was the most consistent cytogenetic abnormality in the human neuroblastomas studied.

Cell Line↗