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Biomedical subjects

C B Pratt

Publications and source records attributed to C B Pratt.

At least 91 records · Page 5Linked to original sources
PubMed1994

Paratesticular rhabdomyosarcoma: delayed effects of multimodality therapy and implications for current management.

BACKGROUND: The combined modalities of surgery, chemotherapy, and radiation therapy have greatly improved the survival rate in childhood paratesticular rhabdomyosarcoma, but the incidence of complications and late side effects is a cause for concern. METHODS: We reviewed the records of 18 patients treated for paratesticular rhabdomyosarcoma at St. Jude Children's Research Hospital between 1962 and 1989. Patients with Group I disease were treated with orchiectomy, retroperitoneal lymph node dissection, and multi-agent chemotherapy; more advanced cases also received radiation therapy with concurrent chemotherapy. RESULTS: Sequelae included esophageal and common bile duct stricture, inguinal nerve entrapment syndrome, and small bowel obstruction. Short stature was found in all children whose spines were irradiated via para-aortic fields (34-37 Gy) prior to puberty. Two of 18 patients died from treatment complications and one from progressive disease. CONCLUSIONS: Multimodality treatment offers an excellent prognosis in paratesticular rhabdomyosarcoma, but is associated with significant morbidity and mortality rates. A discussion of therapy components and their application to disease stages suggests possible approaches to optimizing treatment for this therapy-sensitive malignancy.

Adolescent↗
PubMed1994

Epipodophyllotoxins in the treatment of childhood cancer.

We reported marked biologic activity with the epipodophyllotoxins in phase I/II studies of childhood cancer conducted in the 1970s. We have since extensively used the combination of teniposide and ara-C in the treatment of acute lymphoblastic leukemia (ALL). Initially we treated patients with refractory disease and found that the combination lacked clinical cross-resistance with standard antileukemic drugs. This formed a rationale to move teniposide and/or etoposide to front-line therapy of childhood ALL. The superior results projected for our last trial, an overall cure rate of about 75%, are attributable in part to early use of epipodophyllotoxins. This class of agents is also used extensively in the treatment of newly diagnosed childhood solid tumors, including neuroblastoma, medulloblastoma, rhabdomyosarcoma, and germ-cell tumors. Secondary leukemias following treatment with epipodophyllotoxins have been reported in a small subset of patients. Current data show that the most important risk factor is the schedule of drug delivery, which has led to appropriate protocol modifications.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Chest radiographic features of thoracic metastatic disease in adolescents with colon cancer.

This study describes chest radiographic features of thoracic metastatic disease (TMD) in patients referred for colon cancer to a pediatric oncology hospital. The study group was comprised of 9 patients (7 males, 2 females, age 13-19 years) with serial chest radiographs demonstrating TMD from colon cancer. All patients had a chest radiograph performed within the 2 months prior to death. The median interval from diagnosis of colon cancer to appearance of radiographic TMD was 3 months. Four of nine patients had TMD at presentation, eight of nine patients within 2 years of diagnosis. All abnormalities progressed on serial radiographs. The median interval from appearance of radiographic abnormalities to death was 2 months. Radiographic findings included pleural effusions (n = 6), lymphadenopathy (n = 5), lymphangitic carcinomatosis (n = 4), solitary pulmonary nodule (n = 2), and lobar atelectasis (n = 1). Five patients with pleural effusions initially had right-sided effusions. Radiographic TMD in adolescents with colon cancer usually occurs within 2 years of diagnosis. Once TMD manifests, the prognosis is dismal. Findings include pleural effusions, lymphadenopathy, lymphangitic carcinomatosis, solitary pulmonary nodules, and lobar atelectasis. We suggest that metastatic colon carcinoma should be included in the differential diagnosis for lymphangitic spread of tumor in adolescents.

Adenocarcinoma↗
PubMed1994

Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience.

PURPOSE AND METHODS: We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS: The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P < .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION: A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.

Adolescent↗
PubMed1994

Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors.

PURPOSE: Our aim was to evaluate the pharmacokinetics and pharmacodynamics of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in children, and to determine whether paclitaxel exhibited saturable pharmacokinetics. PATIENTS AND METHODS: We evaluated the pharmacokinetics and pharmacodynamics of paclitaxel (200 to 420 mg/m2) administered as a 24-hour intravenous (i.v.) infusion in a phase 1 study of 30 pediatric patients (age, 2.3 to 22.8 years) with refractory solid tumors. Fourteen serial blood samples were obtained during and up to 48 hours after the infusion, and paclitaxel concentrations were measured by a high-performance liquid chromatography-UV (HPLC-UV) method. Four pharmacokinetic models were compared for their ability to describe the patients' data. RESULTS: Paclitaxel disposition was not consistent with a first-order, two-compartment pharmacokinetic model. Rather, the majority of data sets were best described by a two-compartment model that incorporated both saturable tissue distribution and saturable elimination; a smaller number of patient data sets were best described by models that incorporated either saturable distribution or saturable elimination. Clearance was dose-dependent, with a median clearance at the lower dosages (< 400 mg/m2) of 161 mL/min/m2, and at the highest dosages (> 400 mg/m2) of 123 mL/min/m2 (P = .044). The duration that paclitaxel plasma concentrations exceeded 0.1 mumol/L was highly variable (range, 26 to 71 hours). There was a trend toward higher median area under the concentration-versus-time curve (AUC) in those children with musculoskeletal (72 mumol/L.h; P = .054) or neurologic toxicity (54 mumol/L.h; P = .062) versus those without toxicity (30 mumol/L.h). Toxicity was not significantly correlated with dosage. CONCLUSION: We conclude that paclitaxel distribution and elimination are saturable, and that estimates of paclitaxel systemic exposure correlate better with toxicity than does dosage.

Adolescent↗
PubMed1994

Phase I study of topotecan for pediatric patients with malignant solid tumors.

PURPOSE: To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors. PATIENTS AND METHODS: In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients. RESULTS: Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours. CONCLUSION: Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.

Adolescent↗
PubMed1994

Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity.

PURPOSE: Topotecan pharmacokinetics and pharmacodynamics were studied following a 72-hour continuous infusion in 20 children with cancer (median age, 8 years; range, 3.5 to 18). METHODS: Serial plasma and urine samples were collected during the infusion and for up to 6 hours following the end of infusion. Topotecan (lactone) and total (lactone plus hydroxy acid) concentrations were determined by a sensitive and specific high-performance liquid chromatography (HPLC) assay with fluorescence detection. Using maximum a posteriori-Bayesian modeling, lactone and total plasma concentrations were described separately by a two-compartment model. Hematologic toxicity was expressed as the percent decrease in absolute neutrophil count (ANC) and platelet count. The relation between systemic exposure (SE) and hematologic toxicity was modeled using a sigmoid maximum-effect model. RESULTS: Systemic clearance rates for lactone and total topotecan were (mean +/- SD) 18.5 +/- 7.0 and 6.5 +/- 2.4 L/h/m2, respectively. Urinary recovery of total topotecan was (mean +/- SD) 67.5% +/- 25.2% (n = 12 patients). SE (area under the concentration-time curve from zero to infinity [AUC] or steady-state plasma concentration [Cpss]) to either topotecan lactone or total topotecan was significantly correlated to hematologic toxicity (P < .05). Overall, patients with a higher SE to topotecan experienced greater hematologic toxicity. CONCLUSION: These data demonstrate a relation between systemic exposure to topotecan and clinical effect (myelosuppression). Moreover, these data provide the basis for development of individualized topotecan administration schedules.

Adolescent↗
PubMed1994

Persistent hyperplastic primary vitreous of the eye: imaging findings with pathologic correlation.

Persistent hyperplastic primary vitreous is a rare benign developmental disorder of the globe in which the embryonic hyaloid artery fails to regress normally, resulting in abnormal lenticular development and secondary changes of the retina and globe. This entity often presents a diagnostic challenge as it is the most common intraocular abnormality to be confused with retinoblastoma. Sonography, CT, and MR imaging have been used alone and in combination to diagnose this condition. This essay illustrates the imaging characteristics of persistent hyperplastic primary vitreous in two children with unilateral disease and in one child with bilateral disease as representative cases (Figs. 1-3). Available pathologic correlates also are presented.

Diagnosis, Differential↗
PubMed1994

Malignant parotid tumors in patients previously treated for childhood cancer: clinical and imaging findings in eight cases.

OBJECTIVE: The purpose of this study was to describe the clinical and imaging characteristics of malignant neoplasms of the parotid gland in patients who had been successfully treated for childhood cancer. MATERIALS AND METHODS: Eight cases of parotid carcinoma were identified among survivors of primary childhood cancer treated at two centers. Medical records and imaging studies were reviewed to identify the frequency of second parotid tumors, to assess possible risk factors for their development, and to identify any specific MR or CT features of these tumors. RESULTS: Parotid tumors (mucoepidermoid carcinoma in seven cases and acinar cell carcinoma in one) were diagnosed a median of 9 years (range, 4-16 years) after diagnosis of the initial cancer. These tumors represented 6% of the second cancers diagnosed at one center, whereas salivary gland malignant neoplasms accounted for only 0.08% of primary cancers diagnosed during the same period. The patients ranged from 1 month to 14 years old at the time of initial diagnosis of acute leukemia (n = 7) or neuroblastoma (n = 1). All patients had received multiagent chemotherapy for their initial cancer, and six had received radiation to the head and/or neck. At diagnosis, the parotid tumors were painless, enlarging, periauricular masses without associated facial nerve palsy. Preoperative CT, performed in three cases, showed a solid enhancing parotid soft-tissue mass that was isodense with muscle. MR imaging in two cases showed inhomogeneously enhancing parotid masses. One was isointense with the contralateral parotid gland on T1- and T2-weighted images and hyperintense on contrast-enhanced T1-weighted images; the other was hypointense on T1-weighted images and showed inhomogeneous enhancement that was more intense than in the normal parotid gland. The borders were poorly defined in both these cases. CONCLUSION: Malignant parotid gland tumors are rare in the first two decades of life but may occur more often among patients who have previously received radiation therapy and/or chemotherapy. The CT and MR appearances of these lesions are variable.

Adolescent↗
PubMed1994

Refining therapeutic strategies for patients with resistant Wilm's tumor.

PURPOSE: Despite the excellent prognosis for 90% of patients with Wilms' tumor, survival remains poor among those with recurrent or advanced disease or tumors of unfavorable histology. We sought to identify a chemotherapy regimen for this subset of patients that offers potential efficacy with minimal nephrotoxicity. PATIENTS AND METHODS: Through a review of patients' medical records, we compared the efficacy and nephrotoxicity of ifosfamide, cisplatin, cisplatin/etoposide, and ifosfamide/carboplatin/etoposide (ICE) regimens in 32 patients with recurrent (n = 23), refractory (n = 1), or metastatic (n = 8) Wilms' tumor, including six with tumors having unfavorable histologic features. RESULTS: Single-agent ifosfamide was minimally nephrotoxic and induced responses in three of 11 patients, but none have survived. Cisplatin with or without etoposide induced responses in six of 18 patients with recurrent Wilms' tumor (there is one long-term survivor). Seven of eight patients with newly diagnosed extensive metastatic disease responded to cisplatin/etoposide plus vincristine, dactinomycin, adriamycin, and radiotherapy. This regimen produced three long-term survivors, but was associated with significant nephrotoxicity. The ifosfamide, carboplatin, and etoposide regimen induced responses in four of five patients treated, and had minimal nephrotoxicity. Two remain free of disease progression 22 months after recurrence. CONCLUSIONS: Although long-term survival remains to be determined, the ICE combination appears to be effective against recurrent Wilms' tumor without endangering the patients' single remaining kidney. Myelotoxicity can be ameliorated by administering growth factors. We suggest that ICE chemotherapy be considered for the primary treatment of high-risk patients with Wilms' tumor.

Adolescent↗
PubMed1993

Continuous infusion of interleukin-2 in children with refractory malignancies.

BACKGROUND: The toxicity of interleukin-2 (IL-2) administered by continuous infusion has not been investigated in children. METHODS: This study enrolled 10 boys and 7 girls with refractory malignancy. Recombinant IL-2 was infused continuously for cycles of 120 hours at doses escalating from 3 to 30 x 10(6) IU/m2 per day. RESULTS: A total of 45 cycles was administered. The most common toxicities included fever, anemia, hypotension (usually responsive to fluid bolus), hyponatremia, oliguria, hypoalbuminemia, nausea, thrombocytopenia, vomiting, and weight gain. Most side effects were correlated significantly with a dosage of 18 x 10(6) IU/m2 or more per day. Respiratory distress was infrequent. Two cycles were interrupted due to severe toxicity (hypotension in one case and confusion in another), but there were no fatalities. During infusion, there was a significant nondose-related increase in serum IL-2 receptor levels. Despite this evidence of immunomodulation, no objective tumor response was noted. CONCLUSIONS: Continuous infusion of IL-2 at doses up to 30 x 10(6) IU/m2 per day can be administered safely to children by this method.

Adolescent↗
PubMed1993

Brain metastases in osteosarcoma. Report of a long-term survivor and review of the St. Jude Children's Research Hospital experience.

BACKGROUND: Brain metastasis has been considered a rare event in osteosarcoma, although with prolonged survival an increasing incidence has been suggested. There have been no prior reports of long-term survivors among patients with this complication. METHODS: The authors describe a child treated for osteosarcoma who is alive and free of disease 8 years after the detection of brain metastases. Of 254 patients with primary osteosarcoma referred to St. Jude Children's Hospital between 1962 and 1989, 13 developed brain metastases, all after relapse or recurrence in another site. Concomitant active lung metastases were present in all of the patients except the one long-term survivor, whose pulmonary disease had responded to treatment with cisplatin and doxorubicin. Log-rank analyses were used to compare survival duration and the frequency of brain metastases among patients treated before and after 1982, when effective multiagent therapy was initiated. RESULTS: Log-rank analyses comparing patients treated before and after 1982 showed that the introduction of effective modern therapy improved survival among patients at risk for brain metastases (i.e., those with recurrent and progressive disease, P = 0.007) but was not associated with a statistically significant increase in the frequency of brain metastases (15.5% versus 4.5%, P = 0.125). CONCLUSIONS: Although the outlook for patients with this complication remains bleak, the resolution of brain metastases after eight courses of ifosfamide in the patient described in this article suggests that enrollment of selected patients in Phase II trials is merited.

Adolescent↗
PubMed1993

A phase I study of ifosfamide with Mesna given daily for 3 consecutive days to children with malignant solid tumors.

BACKGROUND: The authors conducted a Phase I dose escalation trial of ifosfamide given daily for 3 consecutive days to 29 children with malignant solid tumors. Twenty-eight of these children had received prior chemotherapy. METHODS: Patients were assigned to dosage cohorts separately on the basis of prior exposure to the platinum alkylating agents cisplatin or carboplatin (n = 20) or the absence of such exposure (n = 9). At least three patients in each category were treated at a starting dosage of 2133 mg/m2/d for 3 days. This dosage represented 80% of the total dose delivered in the prior study of ifosfamide given daily over 5 days with dosage escalation of 20% in subsequent cohorts. RESULTS: Myelosuppression was dose-limiting at the second dosage level (2560 mg/m2/d) for patients previously treated with platinum and at the third dosage level (3072 mg/m2/d) for those not previously treated with platinum. Dose-limiting neurotoxicity was seen at 2560 mg/m2/d for the former group, but was not encountered in the latter group. CONCLUSIONS: Delivery of ifosfamide daily for 3 days is feasible and safe at recommended dosages of 2133 mg/m2/d for children with prior exposure to platinum and 3000 mg/m2/d for those without prior exposure.

Adolescent↗
PubMed1993

A phase I study of ifosfamide given on alternate days to treat children with brain tumors.

BACKGROUND: Ifosfamide with Mesna, given every other day over a 5-day period, was evaluated in 20 children with recurrent or progressive primary brain tumors. METHODS: The patients were assigned to dosage cohorts separated on the basis of prior exposure to cisplatin (n = 10) or the absence of such exposure (n = 10). The initial dose in each treatment arm was 2133 mg/m2 every other day for three doses, which represented 80% of the total dose delivered in our prior study of ifosfamide given daily over 5 days. The dose was escalated by 20% in each of the two subsequent cohorts (2560 mg/m2 and 3072 mg/m2 every other day for three doses). RESULTS: The hematologic toxicity was dose limiting. Prior exposure to cisplatin did not seem to increase the hematologic toxicity. The most frequent and significant metabolic disturbance was hyponatremia, resulting in self-limited seizure activity in three patients. This complication was prevented in subsequent patients by changing the post-ifosfamide hydration fluids from 5% dextrose in quarter normal saline to 5% dextrose in normal saline. CONCLUSIONS: Although no child achieved a complete response, the activity of ifosfamide was demonstrated for a variety of tumors. The recommended dose of ifosfamide in a Phase II study for brain tumors is 3000 mg/m2 given with Mesna every other day for three doses.

Adolescent↗
PubMed1993

Bone tumors other than osteosarcoma after retinoblastoma.

BACKGROUND: The most frequent second malignant neoplasm after retinoblastoma is osteosarcoma, which may be associated with radiation therapy or arise de novo in patients with bilateral retinoblastoma. METHODS: Clinical, pathologic, and diagnostic imaging findings in two patients with Ewing sarcoma (ES) and one with peripheral neuroepithelioma (PN) are presented. RESULTS: Second malignant neoplasms located in the extremities or pelvis were seen 12-18 years after initial diagnosis of unilateral (two patients) or bilateral (one patient) retinoblastoma. The patients with unilateral retinoblastoma were treated by enucleation only; the other received ocular radiation therapy and chemotherapy. To the knowledge of the authors, this is the first documentation of round blue cell tumor after unilateral retinoblastoma. CONCLUSIONS: ES and PN should be included in the differential diagnosis of malignant neoplasms occurring after treatment of unilateral or bilateral retinoblastoma.

Adult↗
PubMed1993

Primary extracranial rhabdoid tumors. Clinicopathologic features and response to ifosfamide.

BACKGROUND: Malignant rhabdoid tumor (MRT) is an aggressive, invariably lethal tumor that is resistant to multimodal therapy. METHODS: The authors reviewed the clinicopathologic features, treatment, and outcome of 13 children (7 boys and 6 girls) with diagnoses of primary extracranial MRT at St. Jude Children's Research Hospital between 1981 and 1990. RESULTS: The median age at diagnosis was 8 months (range, 10 weeks-18 years). Primary sites included the kidney (seven patients), liver (three patients), soft tissue of scapula, posterior mediastinum, and retroperitoneum. Seven patients had metastatic disease (lungs, six patients; cutaneous hemangioma, one patient). Ten patients had surgical resection of primary tumor (complete, nine patients; incomplete, one patient). Eleven patients had chemotherapy with multiple agents. Three of four chemotherapy responses observed were with regimens containing ifosfamide. Partial responses (PR, > 50% reduction in tumor size) were obtained in one patient who received single-agent ifosfamide during disease relapse (PR lasting 2 months), one patient who received a combination of ifosfamide, carboplatin, and etoposide at diagnosis (PR lasting 5 months), and one patient who was treated with bleomycin, cyclophosphamide, doxorubicin, and vincristine at diagnosis (PR lasting 5 months) and subsequently with ifosfamide in combination with carboplatin and etoposide during disease relapse (PR lasting 4 months). All patients died at a median period of 5 months (range, 0.5-30 months) after diagnosis. CONCLUSIONS: Based on this review, the authors recommend using ifosfamide alone or in combination with carboplatin and etoposide in front-line therapy for malignant rhabdoid tumor.

Adolescent↗