Biomedical subjects

Wayne L Furman

Publications and source records attributed to Wayne L Furman.

At least 19 recordsLinked to original sources

PubMed2006

Phase I study of depsipeptide in pediatric patients with refractory solid tumors: a Children's Oncology Group report.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the histone deacetylase inhibitor, depsipeptide, in children with refractory or recurrent solid tumors. PATIENTS AND METHODS: Depsipeptide was administered as a 4-hour infusion weekly for 3 consecutive weeks every 28 days at dose levels of 10 mg/m2, 13 mg/m2, 17 mg/m2, and 22 mg/m2. Pharmacokinetics and histone acetylation studies were performed in the first course. The levels of H3 histone and acetyl-H3 histone were evaluated in peripheral blood mononuclear cells (PBMC) using immunofluorescence techniques. RESULTS: There were 24 patients, and 18 who were assessable were enrolled. DLTs included reversible, asymptomatic T-wave inversions, without any associated changes in troponin levels or evidence of ventricular dysfunction, in the inferior leads in two patients at 22 mg/m2 and in the lateral leads in one patient at 13 mg/m2 (n = 1), and transient asymptomatic sick sinus syndrome and hypocalcemia in one patient at 17 mg/m2. At the MTD (17 mg/m2), the median depsipeptide clearance was 6.8 L/h/m(2) with an area under the plasma depsipeptide concentration-time curve from 0 to infinity of 2,414 ng/mL/h, similar to adults. Accumulation of acetylated H3 histones was seen in all patients in a dose independent manner, with maximal accumulation at a median of 4 hours, (range, 0 hours to 20 hours) after the end of the infusion. No objective tumor responses were observed. CONCLUSION: Depsipeptide is well tolerated in children with recurrent or refractory solid tumors when administered weekly for 3 consecutive weeks every 28 days and inhibits histone deacetylase activity in PBMC in a dose-independent manner. The recommended phase II dose in children with solid tumors is 17 mg/m2.

Acetylation↗

PubMed2006

Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas: the St. Jude Children's Research Hospital experience.

BACKGROUND: Intensified chemotherapy may improve the outcome of patients with high-risk pediatric sarcomas. Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide are highly effective against pediatric sarcomas. The authors investigated the feasibility of administering these agents concomitantly within a defined period. METHODS: In the prospective high-risk sarcoma (HIRISA) Phase II trial HIRISA1, pediatric patients with high-risk sarcomas received 3 cycles of intensive vincristine, ifosfamide, etoposide, cyclophosphamide, and doxorubicin (VACIE) before radiotherapy and/or surgery began at Week 9 with concurrent vincristine, cyclophosphamide, and doxorubicin (Week 9) and vincristine and ifosfamide (Week 12). Three additional cycles of VACIE were then given. After delayed hematologic recovery in the first 11 patients, the protocol was modified (HIRISA2) to delay local control therapy until after 5 cycles of VACIE (to be completed within 18 weeks). Patients who responded to the protocols were eligible for myeloablative consolidation with autologous stem cell support. RESULTS: Eleven of 24 patients (median age, 14.9 years) had Ewing sarcoma family of tumors, 9 patients had rhabdomyosarcoma, and 4 patients had unresectable desmoplastic small round cell tumors. Seven of 13 patients on HIRISA2, but none of 11 patients on HIRISA1, completed therapy within the specified time. Reversible Grade 4 myelosuppression was the most common toxicity. Major nonhematologic toxic effects were mucositis, nutritional impairment, hypotension, and peripheral neuropathy. Three patients died of toxicity. The 5-year survival and 5-year event-free survival estimates both were 45.8% +/- 11.2%. CONCLUSIONS: The feasibility of administering intensive chemotherapy regimens like VACIE was dependent in part on the timing of local control therapy. This regimen was associated with significant toxicity.

Adolescent↗

PubMed2006

Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors.

PURPOSE: Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. PATIENTS AND METHODS: In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. RESULTS: Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60 mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x h/mL, respectively; P = .030). CONCLUSION: Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.

Administration, Oral↗

PubMed2006

Familial adenomatous polyposis in two brothers with hepatoblastoma: implications for diagnosis and screening.

Two brothers with hepatoblastoma were noted to have a family history of early onset colon cancer. Genetic testing of the younger brother revealed a deletion in exon 15 of the adenomatous polyposis coli (APC) gene (2710-2711delAG), consistent with a diagnosis of familial adenomatous polyposis (FAP). We review the clinical and molecular aspects of the relationship between hepatoblastoma and FAP, and the implications for diagnostic testing and cancer screening in affected patients.

Adenomatous Polyposis Coli↗

PubMed2006

Pilot study to evaluate MYCN expression as a neuroblastoma cell marker to detect minimal residual disease by RT-PCR.

This pilot study was performed to determine whether MYCN expression warrants further investigation as a tumor marker to detect low levels of residual neuroblastoma (NB). Seven NB cell lines and 30 bone marrow (BM) samples from patients with high-risk NB were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) for MYCN expression, and for the established NB marker tyrosine hydroxylase. MYCN was expressed in all 7 NB cell lines, but not in normal peripheral blood, CD34 cells, or BM. In dilution studies using cell lines with or without DNA amplification of MYCN, 1 NB cell in 10 to 10 nucleated blood cells was detectable by RT-PCR. MYCN was identified in all 21 BM samples in which tumor cells were identified by histologic examination, including 4 samples in which tyrosine hydroxylase was not detected. Additionally, expression of both markers was detected in 5 samples that were negative by histology but presumably contained low levels of tumor cells, consistent with the greater sensitivity of RT-PCR compared with morphologic methods. Detection of MYCN RNA was independent of MYCN DNA amplification status. The selective expression of MYCN in tumor cells, and the sensitivity of detection of MYCN by RT-PCR noted in this and other studies, supports further evaluation of MYCN as a NB marker for molecular detection of minimal residual disease.

Biomarkers, Tumor↗

PubMed2005

The impact of early resection of primary neuroblastoma on the survival of children older than 1 year of age with stage 4 disease: the St. Jude Children's Research Hospital Experience.

BACKGROUND: It remains unclear whether primary tumor resection benefits patients with metastatic neuroblastoma. The authors assessed the impact of extent and timing of resection on outcome in these patients. METHODS: The authors reviewed the records of 124 patients > 1 year of age at diagnosis of International Neuroblastoma Staging System Stage 4 neuroblastoma. The survival estimates of those who did and did not have a gross total resection (GTR) and of those who had initial versus delayed GTR were compared. Surgical complications were reviewed. RESULTS: The 5-year survival estimates were comparable for the 90 patients who had a GTR and the 17 who underwent surgery but did not have a GTR (29.9% +/- 5.1% [standard error] vs. 29.4% +/- 10.1%). The 7 patients who underwent GTR at the time of diagnosis had a higher 5-year survival estimate than the 83 patients who had a GTR after induction chemotherapy (83.3% +/- 13.9% vs. 25.2% +/- 5.0%) (P = 0.001). Five-year event-free survival estimates were similarly higher in the initial-GTR group (57.1% +/- 18.7% vs. 14.5% +/- 4.2%) (P = 0.002). These two groups did not differ significantly in age at diagnosis (P = 0.118), site of primary tumor (P = 0.34), MYCN amplification status (P = 1), serum lactate dehydrogenase activity at diagnosis (P = 0.34), or treatment protocol (P = 0.22). Twenty-two (21%) patients had a surgical complication. CONCLUSIONS: In this small cohort of patients with metastatic neuroblastoma, GTR at the time of diagnosis offered a survival benefit. Further prospective studies are warranted before this approach can be applied to all patients with metastatic neuroblastoma.

Adolescent↗

PubMed2005

End-of-life care preferences of pediatric patients with cancer.

PURPOSE: The viewpoint of the terminally ill child at the time of an end-of-life decision has not been formally investigated. We identified the preferences of children and adolescents with advanced cancer about their end-of-life care and the factors that influenced their decisions. PATIENTS AND METHODS: Pediatric patients 10 or more years of age were interviewed within 7 days of participating in one of the following three end-of-life decisions: enrollment onto a phase I trial (n = 7), adoption of a do not resuscitate order (n = 5), or initiation of terminal care (n = 8). The patient, a parent, and the primary pediatric oncologist were interviewed separately by using open-ended interview questions. RESULTS: Twenty patients, aged 10 to 20 years (mean, 17 years and 4 months), with a refractory solid tumor (n = 12), brain tumor (n = 4), or leukemia (n = 4) participated. Eighteen patients (90%) accurately recalled all of their treatment options and identified their own death as a consequence of their decision. The factors that were most frequently identified included the following: for patients, caring about others (n = 19 patients); for parents, the child's preferences (n = 18 parents); and for physicians, the patient's prognosis and comorbid conditions (n = 14 physicians). CONCLUSION: These children and adolescents with advanced cancer realized that they were involved in an end-of-life decision, understood the consequences of their decision, and were capable of participating in a complex decision process involving risks to themselves and others. The decision factors most frequently reported by patients were relationship based; this finding is contrary to existing developmental theories.

Adolescent↗

PubMed2005

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.

Administration, Oral↗

PubMed2005

Typhlitis in childhood cancer.

BACKGROUND: Typhlitis is increasingly recognized in children undergoing chemotherapy but is poorly characterized. The authors investigated the demographic, clinical, and imaging (ultrasonography and computed tomography [CT] scans) variables related to the diagnosis, risk, and outcome of typhlitis. METHODS: The authors reviewed the records of patients who had typhlitis (bowel wall thickness > or = 0.3 cm plus clinical findings) during treatment at St. Jude Children's Research Hospital (Memphis, TN) between 1990 and 2001. They assessed whether duration of typhlitis was related to bowel wall thickness, extent of colonic involvement, ascites, demographics, primary diagnosis, symptoms of typhlitis, or duration of neutropenia. To identify risk factors for typhlitis, the authors compared the demographic data and previous drug therapy of 78 patients who had typhlitis and 1231 identically treated children who did not. RESULTS: Of 3171 children, 83 (2.6%) developed typhlitis. Frequent symptoms were abdominal pain (91%), fever (84%), abdominal tenderness (82%), and diarrhea (72%). Twelve percent of the patients were not neutropenic. Duration of typhlitis was associated with bowel wall thickness measured by ultrasonography (n = 68; P = 0.05) but not CT scan (n = 48; P = 0.67) and was associated with duration of neutropenia (P = 0.02), fever (P = 0.01), and abdominal tenderness (P = 0.04). Age >16 years at cancer diagnosis was the only demographic factor associated with typhlitis (P = 0.03). Two patients died of typhlitis. CONCLUSIONS: Ultrasonography was a useful imaging modality for children with suspected typhlitis. The classic triad of abdominal pain, fever, and neutropenia may be absent. The severity of typhlitis was related to the duration of neutropenia and the presence of fever or abdominal tenderness.

Adolescent↗

PubMed2005

Improved response in high-risk neuroblastoma with protracted topotecan administration using a pharmacokinetically guided dosing approach.

PURPOSE: To estimate the response rate and toxicity associated with intravenous topotecan when it is administered on a protracted schedule according to a pharmacokinetically guided dosing approach to treat childhood high-risk neuroblastoma. PATIENTS AND METHODS: In this prospective phase II trial, topotecan was administered intravenously daily for 5 days for each of 2 consecutive weeks for two cycles. On the basis of topotecan systemic clearance, doses were individualized to attain a single-day topotecan lactone area under the plasma concentration-time curve (AUC) of 80 to 120 ng/mL . h. Patients subsequently received standard treatment. RESULTS: Both cycles were administered to 28 (93%) of the 30 enrolled patients (median age, 3.1 years). Target topotecan AUCs were achieved in 92 (72%) of the 127 measurements conducted after pharmacokinetically guided adjustment; the median dosage required to achieve target AUCs was 2.7 mg/m(2) (range, 0.95 to 3.8 mg/m(2)). The response rate was 60% (95% CI, 41% to 77%); there were one complete and 17 partial responses. No patient experienced disease progression during initial topotecan therapy. Primary tumor volumes decreased (median decrease, -58.2%; range, -95.1% to -4.9%) in the 26 patients with available size data. Homovanillic acid levels in 16 (89%) of 18 patients and vanillylmandelic acid levels in 14 (78%) of 18 patients were lower (P = .002 and P = .018, respectively) after topotecan therapy. Reversible grade 4 myelosuppression occurred in all patients, but no deaths occurred as a result of infection or toxicity. CONCLUSION: Topotecan is active against neuroblastoma when it is administered on a protracted schedule and targeted systemic exposure is achieved.

Adolescent↗

PubMed2005

The feasibility of adjuvant interferon alpha-2b in children with high-risk melanoma.

BACKGROUND: It has been shown that induction high-dose interferon alpha-2b (IFN-alpha-2b) followed by maintenance therapy improves recurrence-free survival in adults with high-risk, resected melanoma. In this study, the feasibility and toxicity of this regimen were evaluated in newly diagnosed pediatric patients with Stage III melanoma involving regional lymph nodes. METHODS: Fifteen patients age <or=18 years with newly diagnosed Stage III melanoma were enrolled on an institutional protocol. Patients were treated with wide local excision, sentinel lymph node biopsy, lymph node dissection, and adjuvant biotherapy, consisting of induction therapy with 20 million IU/m2 per day IFN-alpha-2b intravenously 5 times per week for 4 weeks followed by maintenance therapy with IFN-alpha-2b 10 million IU/m2 per day subcutaneously 3 times per week for 48 weeks. Patients were monitored for toxicity and tumor recurrence. RESULTS: All patients completed induction therapy, and nine patients completed maintenance therapy. Three patients currently are receiving maintenance, 2 patients developed recurrent disease on maintenance therapy, and 1 patient stopped maintenance therapy 5 weeks early. During induction therapy, Grade 3-4 toxicities included 14 episodes of neutropenia in 11 patients, 3 episodes of leukopenia in 2 patients, and 6 episodes of liver transaminase elevations in 5 patients. Dose modifications were required in four patients. During maintenance therapy, Grade 3-4 toxicities included 23 episodes of neutropenia in 10 patients and 2 episodes of liver transaminase elevations in 2 patients. Three patients required dose modifications. All toxicities were reversible with interruption or dose modification of therapy, and no patients were taken off study due to toxicity. CONCLUSIONS: High dose IFN-alpha-2b for 4 weeks followed by a lower dose maintenance phase for 48 weeks was feasible in children with Stage III melanoma and was associated with tolerable toxicity.

Adolescent↗

PubMed2005

Radiographic assessment of resectability of locoregional disease in children with high-risk neuroblastoma during neoadjuvant chemotherapy.

BACKGROUND: The optimal timing for attempting removal of the primary tumor and regional disease in patients with high-risk neuroblastoma is uncertain. The purpose of this study was to evaluate resectability of the primary tumor and regional disease, as determined radiographically, in children with high-risk neuroblastoma during neoadjuvant chemotherapy. PROCEDURE: Patients enrolled in our institutional high-risk neuroblastoma protocol were evaluated prospectively by CT scan and/or MRI to determine the resectability of their primary tumor and regional disease at diagnosis, after two cycles of experimental therapy and after standard induction therapy. Tumors were considered to be unresectable if there was significant involvement with major vascular structures or contiguous organs, or would likely require nephrectomy to remove the entire tumor. RESULTS: Twenty-four patients were referred prior to surgery for treatment of high-risk neuroblastoma. Seven of 24 (29%) patients were felt to be resectable at diagnosis, with an additional 9 patients becoming resectable after the initial experimental therapy. Thus, overall, 16 of 24 (67%) patients were felt to be resectable by the completion of the initial therapy. Only four additional patients of the remaining eight were considered resectable after the completion of standard induction therapy. CONCLUSIONS: Based on these data, we conclude that complete resection of the primary tumor and regional disease in children with high-risk neuroblastoma can be performed after an initial phase therapy in the majority of patients. Since earlier tumor removal may decrease the chance for the subsequent development of chemotherapy-resistant disease, we are recommending surgical resection as soon as the locoregional disease appears to be resectable.

Adolescent↗

PubMed2004

Combined use of erythropoietin and granulocyte colony-stimulating factor does not decrease blood transfusion requirements during induction therapy for high-risk neuroblastoma: a randomized controlled trial.

PURPOSE: To evaluate the efficacy of recombinant erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) in reducing blood transfusion requirements and stimulating hematopoiesis in children with high-risk neuroblastoma. PATIENTS AND METHODS: Thirty-eight patients given six cycles of intensive induction chemotherapy for high-risk neuroblastoma were randomized to receive G-CSF (n = 20) or G-CSF + EPO (n = 18). Cytokines were given subcutaneously each day, starting 24 hours after each chemotherapy cycle and continuing until 48 hours before the start of the next cycle. The primary end point was the effect of EPO on total red cell transfusion requirements during induction therapy. RESULTS: Patients who received G-CSF + EPO had a higher red cell transfusion requirement (median, 161.0 mL/kg) than did those who received G-CSF alone (median, 106.6 mL/kg; P =.005). In addition, among patients given transfusions for hemoglobin < or = 8 g/dL, those in the G-CSF + EPO group received more red cell transfusions than did those given G-CSF alone (median per patient, 10 v 8, respectively; P =.044). The two treatment groups had similar cumulative durations of neutropenia, incidences of febrile neutropenia, platelet transfusion requirements, and numbers of platelet transfusions; they also received induction chemotherapy for similar durations and had similar probabilities of progression-free survival and overall survival. CONCLUSION: The addition of EPO to the G-CSF regimen provides no benefit for patients receiving intensive induction chemotherapy for high-risk neuroblastoma.

Adolescent↗

PubMed2004

Phase I trial of tirapazamine and cyclophosphamide in children with refractory solid tumors: a pediatric oncology group study.

PURPOSE: To determine the dose limiting toxicity (DLT), maximum-tolerated dose (MTD), and pharmacokinetic profile of tirapazamine (Sanofi Synthelabo Research, Malvern, PA) combined with cyclophosphamide in children with recurrent solid tumors. PATIENTS AND METHODS: Patients received a 2-hour infusion of tirapazamine, followed by 1,500 mg/m(2) cyclophosphamide, and mesna once every 3 weeks. Dose escalation of tirapazamine began at 250 mg/m(2) and was increased by 30% in subsequent cohorts. If DLT was hematologic, less-heavily pretreated patients were to be enrolled until their DLTs were encountered, and MTDs defined. Pharmacokinetic profiles were also characterized. RESULTS: Twenty-three patients were enrolled onto the study. Pharmacokinetic data were calculated for 22 patients. Prolonged neutropenia was the DLT at 420 mg/m(2) in heavily pretreated patients. Grade 3, reversible ototoxicity was the DLT in less-heavily pretreated patients at 420 mg/m(2). Two (one with neuroblastoma and one with rhabdomyosarcoma) had partial responses. One child with neuroblastoma had prolonged stable disease (10 cycles) at a dose of 250 mg/m(2). This patient had disease detectable in the bone marrow only and all evidence of bone marrow involvement resolved for 17 cycles of therapy. Four other patients had stable disease. An apparent dose-proportional increase in tirapazamine maximal concentration and area under the curve(last) was observed. Tirapazamine clearance, volume of distribution at steady-state, and terminal half-life did not appear to be dose-dependent. CONCLUSION: The recommended dose of tirapazamine given with 1,500 mg/m(2) of cyclophosphamide once every 3 weeks is 325 mg/m(2). Neutropenia and ototoxicity were dose-limiting. Based on early evidence of antitumor activity, additional studies appear warranted.

Adolescent↗

PubMed2004

Phase I and pharmacokinetic study of topotecan administered orally once daily for 5 days for 2 consecutive weeks to pediatric patients with refractory solid tumors.

PURPOSE: We conducted a phase I trial of the injectable formulation of topotecan given orally once daily for 5 days for 2 consecutive weeks (qd x 5 x 2) in pediatric patients with refractory solid tumors. PATIENTS AND METHODS: Cohorts of two to six patients received oral topotecan at 0.8, 1.1, 1.4, 1.8, and 2.3 mg/m(2)/d every 28 days for a maximum of six courses. Twenty patients (median age, 10.6 years) received a total of 51 courses. Eight patients received topotecan capsules during course 2 only. RESULTS: Dose-limiting toxicity occurred at 2.3 mg/m(2)/d and consisted of prolonged grade 4 neutropenia (n = 2), grade 3 stomatitis as a result of radiation recall (n = 1), grade 3 hemorrhage (epistaxis) in the presence of grade 4 thrombocytopenia (n = 1), and grade 3 diarrhea in the presence of Clostridium difficile infection (n = 1). Dose-limiting, prolonged grade 4 neutropenia and thrombocytopenia occurred in one patient at 1.4 mg/m(2)/d. Infrequent toxicities were mild nausea, vomiting, elevated liver ALT or AST, and rash. The maximum-tolerated dosage was 1.8 mg/m(2)/d; the mean (+/- standard deviation) area under the plasma concentration-time curve for topotecan lactone at this dosage was 20.9 +/- 8.4 ng/mL. h. The population mean (+/- standard error) oral bioavailability of the injectable formulation was 0.27 +/- 0.03; that of capsules was 0.36 +/- 0.06 (P =.16). Disease stabilized in nine of 19 assessable patients for 1.5 to 6 months. CONCLUSION: Oral topotecan (1.8 mg/m(2)/d) on a qd x 5 x 2 schedule is well tolerated and warrants additional testing in pediatric patients.

Administration, Oral↗

PubMed2004

Tumor recurrence at thoracostomy tube insertion sites: a report of two pediatric cases.

Recurrence of thoracic malignant tumors at port sites used for thoracoscopic procedures in adults have been described. However, there are no reports of tumor recurrence at thoracostomy tube or thoracoscopic trocar insertion sites after operation for thoracic malignancies in children. The authors report 2 cases of tumor recurrence at thoracostomy tube insertion sites after intraoperative gross spillage of pleuropulmonary blastoma and malignant epithelial thymoma and discuss approaches that may potentially prevent this devastating complication.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Protracted intermittent schedule of topotecan in children with refractory acute leukemia: a pediatric oncology group study.

PURPOSE: To determine dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of a protracted, intermittent schedule of daily 30-minute infusions of topotecan (TPT) for up to 12 consecutive days, every 3 weeks, in children with refractory leukemia. PATIENTS AND METHODS: Forty-nine children were enrolled onto this phase I trial (24 with acute nonlymphoblastic leukemia [ANLL] and 25 with acute lymphoblastic leukemia [ALL]). TPT dosage was escalated from 2.0 to 5.2 mg/m(2)/d for 5 days and 2.4 mg/m(2)/d from 7 days to the same dose for 9 and 12 days in cohorts of three to six patients when no DLT was identified. TPT pharmacokinetics were studied in 33 children once or twice (first and last doses in patients who received TPT for > 7 days). RESULTS: Seventy assessable courses of TPT were administered to 49 children who had refractory leukemia. DLTs were typhlitis, diarrhea, and mucositis, and the MTD was 2.4 mg/m(2)/d for 9 days in this group of heavily pretreated children. In 33 patients, the median TPT lactone clearance after the first dose was 19.2 L/h/m(2) (range, 9.4 to 45.9 L/h/m(2)) and did not change during the course. There were significant responses (one complete response [CR] and four partial responses [PR] in patients with ANLL and one CR and two PRs in patients with ALL), and all but one were at dosages of TPT given for at least 9 days. CONCLUSION: The MTD was 2.4 mg/m(2)/d for 9 days. Further testing is warranted of TPT's schedule dependence in children with leukemia.

Adolescent↗

PubMed2002

Perianal rhabdomyosarcoma presenting as a perirectal abscess: A report of 11 cases.

BACKGROUND PURPOSE: The organs and soft tissues of the pelvis are some of the most common primary sites for rhabdomyosarcoma (RMS) in children and adolescents. In most cases a mass is detectable on clinical examination, and the initial concern is focused on the possibility of a neoplasm. The current report concerns 11 patients, each presented with a painful perineal-perianal mass suggesting an abscess to the extent that each one of these patients was treated initially with antibiotics or incision and drainage for several weeks to months before the pathologic diagnosis of RMS was established. METHODS: The authors reviewed the clinical histories of all patients with perirectal/perianal RMS from their respective institutions to identify cases in which the initial clinical diagnosis or impression was that of a perirectal abscess. Pathologic material was reviewed in all cases. RESULTS: Eleven patients, 7 of whom were girls, ranged in age from 1 to 16 years at diagnosis (median age, 14 years). Fever accompanied the clinical presentation in 2 patients. None of the patients had a past medical history of illness that may have predisposed them to a perirectal abscess, although one patient had a family history of inflammatory bowel disease. Duration of symptoms ranged from 1 month to 1 year (mean, 4.6 months). Each patient presented with a tender perianal/perineal nodule or mass. Inguinal adenopathy was present in 6 patients at diagnosis. White blood cell counts ranged from 6,600/mm(3) to 24,500/mm(3). LDH levels ranged from 414 to 3,432 U/L. The average time from presentation to pathologic diagnosis of RMS was 2.1 months. Nine of the 11 cases showed an alveolar pattern. All were high-stage disease. Of 7 patients with follow-up longer than 1 year, 2 (29%) are alive without disease. CONCLUSION: This report presents the need to consider the possibility of a malignant neoplasm, in this case RMS, in a child or adolescent with a putative perirectal abscess that fails to respond in the expected manner to incision and drainage and antibiotic therapy.

Abscess↗