Biomedical subjects

M D Krailo

Publications and source records attributed to M D Krailo.

At least 37 records · Page 2Linked to original sources

PubMed1998

Phase II trial of topotecan administered as 72-hour continuous infusion in children with refractory solid tumors: a collaborative Pediatric Branch, National Cancer Institute, and Children's Cancer Group Study.

The antitumor activity of topotecan administered as a 72-h continuous i.v. infusion was evaluated in children with refractory neuroblastoma and sarcomas of soft tissue and bone. We also attempted to increase the dose intensity of topotecan by including an intrapatient dose escalation in the trial design. Ninety-three children (85 eligible and evaluable for response) with recurrent or refractory neuroblastoma, osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, or other soft-tissue sarcomas received topotecan administered as a 72-h i.v. infusion every 21 days. The initial dose was 1.0 mg/m2/day, with subsequent intrapatient dose escalation to 1.3 mg/m2/day for those patients who did not experience dose-limiting toxicity after their first cycle of topotecan. There was one complete response in a patient with neuroblastoma (n = 26) and one partial response in a patient with Ewing's sarcoma/peripheral neuroectodermal tumor (n = 25). No complete or partial responses were observed in 17 patients with osteosarcoma, 15 patients with rhabdomyosarcoma, or 2 patients with other soft-tissue sarcomas; however, 8 patients had prolonged (15-48 weeks) stable disease while receiving topotecan. Topotecan was well tolerated. The most commonly observed toxicities were myelosuppression (dose-limiting) and nausea and vomiting. Intrapatient dose escalations were performed in 68% of the patients who received more than one cycle of topotecan, and 1.3 mg/m2/day was tolerated by 79% of the patients who received the higher dose and were evaluable for hematological toxicity. In conclusion, topotecan administered as a 72-h continuous infusion every 21 days is inactive (objective response rate, < 20%) in children with refractory or recurrent neuroblastoma and sarcomas of soft tissue or bone.

Adolescent↗

PubMed1998

Pharmacokinetic and pharmacodynamic studies of fludarabine and cytosine arabinoside administered as loading boluses followed by continuous infusions after a phase I/II study in pediatric patients with relapsed leukemias. The Children's Cancer Group.

The sequential administration of fludarabine followed by cytosine arabinoside (ara-C) has demonstrated significant synergistic effects against the CEM human leukemic cell line. This in vitro synergism was investigated in a Phase I trial in pediatric patients with relapsed acute leukemia. The optimum concentrations of 9-beta-D-arabinofuranosyl 2-fluoroadenine and ara-C necessary to achieve significant drug synergism from in vitro studies were between 10 and 20 microM. Fludarabine was infused at a dose to attain a target plasma concentration of 10 microM for 48 h, followed by a continuous infusion of escalated ara-C doses to maintain plasma ara-C concentrations of 10, 12.5, 15, or 17.5 microM for 72 h. Thirteen patients with acute lymphocytic leukemia and 18 with acute myelocytic leukemia were entered into the study, 30 of whom were clinically evaluable for toxicity. Pharmacokinetic and pharmacodynamic studies were performed on specimens from 20 patients. The optimal 9-beta-D-arabinofuranosyl 2-fluoroadenine and ara-C concentrations in plasma were easily achieved after continuous infusion regimens of both drugs. Cellular ara-CTP is augmented 5-8-fold in leukemic cells from patients receiving fludarabine phosphate treatment followed by ara-C. The maximum tolerated plasma concentrations for this combination regimen was 10 microM fludarabine for 48 h followed by 72 h of 15 microM ara-C, which were achieved at dose level 3. A significant number of responses were also seen. Nine of 18 evaluable patients (50%) with acute myelocytic leukemia achieved complete or partial responses, and 3 of 9 evaluable patients with acute lymphocytic leukemia achieved complete or partial responses. Fludarabine and ara-C successfully eradicated bone marrow disease in 16 of 27 patients (59%), 23 patients of which had been treated previously with high-dose ara-C. These results verified the synergistic effect fludarabine exhibited in augmenting ara-CTP concentrations in patients' leukemic blasts, thus improving the clinical response in relapsed pediatric leukemias.

Adolescent↗

PubMed1997

A phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus interleukin-2 in children with refractory neuroblastoma: a report of the Children's Cancer Group.

BACKGROUND: The murine monoclonal antibody (MoAb) 14.G2a recognizes GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and facilitates antibody dependent cellular cytotoxicity (ADCC) in vitro. When given in vivo, interleukin-2 (IL-2) can increase ADCC by enhancing the activity and number of circulating lymphocytes. METHODS: Thirty-three pediatric patients with GD2 positive malignancies, ranging in age from 2 to 17 years (median, 9.9 years), received IL-2 and 14.G2a in this Phase I/IB study of the Children's Cancer Group (CCG) and were monitored for toxicities and response to therapy. Seven of these patients also received granulocyte-macrophage-colony stimulating factor. RESULTS: The maximum tolerated dose (MTD) of 14.G2a with IL-2 was 15 mg/m2/day. The most prevalent Grade 3-4 toxicities were generalized pain (n = 14 [42%]) and fever without documented infection (n = 17 [52%]). IL-2 was thought to be the causative agent in most cases of fever. Toxicities attributed to 14.G2a included pain, allergic or anaphylactic reactions, and rash. Human antimouse antibodies were demonstrated in 9 of 21 evaluated patients. One patient with neuroblastoma had a partial response, and one patient with osteosarcoma had a complete response. Immunocytology demonstrated that the number of neuroblastoma cells in bone marrow decreased in three patients. CONCLUSIONS: The murine MoAb 14.G2a was well tolerated at the MTD and appeared to have some antitumor activity. Further development of this approach will involve additional engineered forms of the antibody as well as testing in the adjuvant and minimal residual disease setting.

Adjuvants, Immunologic↗

PubMed1997

A phase II study of carboplatin as a treatment for children with acute leukemia recurring in bone marrow: a report of the Children's Cancer Group.

BACKGROUND: Carboplatin is an analogue of cisplatin with less nonhematologic toxicity and a similar spectrum of antineoplastic activity. Although cisplatin has not been found to be an active agent against leukemia, carboplatin-induced complete remissions have been observed in adults with acute myelogenous leukemia (AML), and antileukemic activity has been observed in a Phase I trial involving children with acute lymphoblastic leukemia (ALL) and AML. Therefore, a pediatric Phase II study was undertaken to determine the degree of activity of carboplatin in childhood ALL and AML. METHODS: Between October 1991 and November 1994, the Children's Cancer Group conducted a Phase II study of carboplatin given by 5-day continuous intravenous infusion to children with acute leukemia recurring in bone marrow. RESULTS: Minimal antileukemic activity was demonstrated in patients with ALL and AML. One of 21 eligible patients with ALL achieved a partial response. Of 23 eligible patients with AML, including 1 patient with chronic myelogenous leukemia in blast crisis, 1 had hypocellular M1 bone marrow with a platelet count of 15,000/mm3, and 2 achieved partial responses. Nonhematologic toxicities, which were infrequent, included mild hepatic and renal dysfunction. CONCLUSIONS: In this pediatric Phase II trial of carboplatin as a treatment for acute leukemia, minimal activity was demonstrated in patients with ALL and AML recurring in bone marrow. Further evaluation of carboplatin as a treatment for childhood leukemia, using the dose schedule of 216 mg/m2/day given by 5-day continuous intravenous infusion, does not appear warranted.

Adolescent↗

PubMed1997

Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group.

PURPOSE: The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival. PATIENTS AND METHODS: Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP). RESULTS: The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not. CONCLUSION: EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.

Adolescent↗

PubMed1997

Timing and magnitude of decline in alpha-fetoprotein levels in treated children with unresectable or metastatic hepatoblastoma are predictors of outcome: a report from the Children's Cancer Group.

PURPOSE: We analyzed data on 31 children with primary unresectable or metastatic hepatoblastoma (HB) to investigate possible prognostic correlations between the serum level of alpha-fetoprotein (AFP), its changes during treatment, and outcome. PATIENTS AND METHODS: Patients were treated according to the Children's Cancer Group (CCG) protocol 823F, which included an initial surgery before eight courses of chemotherapy that consisted of cisplatin immediately followed by a continuous infusion of doxorubicin. Four courses were given before and four after the second surgery. AFP levels were measured before treatment, before and after second surgery, and at the end of treatment. RESULTS: Twenty-four of 31 patients showed a decline of > or = 1 log in AFP levels before second surgery (early responders). By the end of treatment, there were 16 patients, all early responders, without clinical or radiographic evidence of tumor and with normal AFP levels. Fifteen of those 16 had a decline of > or = 2 logs in AFP before second surgery (large early response). Of the 15 patients who failed to respond to treatment, 10 died, among whom only one patient had a large early response. A large early response was the strongest independent predictor of outcome in a univariate and multivariate Cox regression model, and patients with such a response had the best survival (P < .0001). CONCLUSION: For children with unresectable or metastatic HB, early changes in AFP levels are a reliable predictor of outcome and can be used for identification of poor responders to treatment, ie, patients whose AFP level fails to decrease 2 logs before second surgery should be considered for alternative treatment.

Child↗

PubMed1997

Phase I trial of docetaxel administered as a 1-hour infusion in children with refractory solid tumors: a collaborative pediatric branch, National Cancer Institute and Children's Cancer Group trial.

PURPOSE: A phase I trial of docetaxel was performed to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with refractory solid tumors. PATIENTS AND METHODS: Forty-four children received 103 courses of docetaxel administered as a 1-hour intravenous infusion every 21 days. Doses ranged from 55 to 150 mg/m2, MTD was defined in heavily pretreated and less heavily pretreated (< or = 2 prior chemotherapy regimens, no prior bone marrow transplantation [BMT], and no radiation to the spine, skull, ribs, or pelvic bones) patients. RESULTS: Dose-related neutropenia was the primary dose-limiting toxicity. The MTD in the heavily pretreated patient group was 65 mg/m2, but the less heavily pretreated patients tolerated a significantly higher dose of docetaxel (maximum-tolerated dose, 125 mg/m2). Neutropenia and constitutional symptoms consisting of malaise, myalgias, and anorexia were the dose-limiting toxicities at 150 mg/m2 in the less heavily pretreated patients. Thrombocytopenia was not prominent, even in patients who experienced dose-limiting neutropenia. Common nonhematologic toxicities of docetaxel included skin rashes, mucositis, and mild elevations of serum transaminases. Neuropathy was uncommon. Peripheral edema and weight gain were observed in two of five patients who received more than three cycles of docetaxel. A complete response (CR) was observed in one patient with rhabdomyosarcoma, a partial response (PR) in one patient with peripheral primitive neuroectodermal tumor (PPNET), and a minimal response (MR) in two patients with PPNET. Three of the four responding patients were treated at doses > or = 100 mg/m2. CONCLUSION: The recommended phase II dose of docetaxel administered as a 1-hour intravenous infusion in children with solid tumors in 125 mg/m2. Because neutropenia was the dose-limiting toxicity and thrombocytopenia was mild, further escalation of the dose should be attempted with granulocyte colony-stimulating factor (G-CSF) support.

Adolescent↗

PubMed1997

Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children's Cancer Group.

PURPOSE: The Children's Cancer Group (CCG) undertook a phase I study (CCG-0922) to determine a tolerable dose of idarubicin given with fludarabine and cytarabine in children with relapsed or refractory leukemia. The phase I study was extended to a limited phase II study to assess the activity of this combination in children with acute myelogenous leukemia (AML). PATIENTS AND METHODS: This was a multiinstitutional study within the CCG. Eleven patients were entered onto the phase I study: seven with AML, three with acute lymphoblastic leukemia (ALL), and one with chronic myelogenous leukemia (CML). The maximal-tolerated dose (MTD) of fludarabine and cytarabine determined in a previous study was a fludarabine loading dose (LD) of 10.5 mg/m2 followed by a continuous infusion (CI) of 30.5 mg/m2/24 hours for 48 hours, followed by cytarabine LD 390 mg/m2, then CI 101 mg/m2/h for 72 hours. Idarubicin was given at three dose levels: 6, 9, and 12 mg/m2 intravenously (I.V.) on days 0, 1, and 2. The phase II portion of the trial included 10 additional patients with relapsed or refractory AML. RESULTS: A dose of idarubicin 12 mg/m2/d for 3 days given in combination with fludarabine and cytarabine was tolerated. The major toxicity encountered was hematologic. Nonhematologic toxicities included transaminase elevations, hyperbilirubinemia, and infections. Eight of 10 patients with AML in the phase II portion (12 mg/m2 idarubicin) achieved a complete remission (CR). CONCLUSION: This combination is active in patients with relapsed or refractory AML. The major toxicity encountered is hematologic. This regimen may be useful therapy for AML and should be compared with standard induction therapy in children with newly diagnosed AML.

Acute Disease↗

PubMed1996

A phase II study of thioTEPA in children with recurrent solid tumor malignancies: a Children's Cancer Group study.

A Phase II study of thioTEPA was performed by the Children's Cancer Group. ThioTEPA was administered intravenously every three weeks, at a dose of 65 mg/m2. Pediatric patients with recurrent sarcomas were targeted, but patients with other tumor diagnoses were also eligible. Toxicity was primarily hematopoietic, with thrombocytopenia being predominant. ThioTEPA did not demonstrate significant activity in the target tumor groups evaluated.

Adolescent↗

PubMed1995

An exploratory analysis of risk factors for childhood malignant germ-cell tumors: report from the Childrens Cancer Group (Canada, United States).

A study of 105 patients with childhood malignant germ-cell tumors (MGCT) and 639 community controls was conducted utilizing a large epidemiologic database collected by the Childrens Cancer Group from 25 member institutions in the United States and Canada. This study was designed to explore the risk factors of this malignancy whose etiology remains poorly understood. A structured, self-administered questionnaire was used to collect exposure information, and data were analyzed using an unconditional logistic regression model with adjustment for relevant confounders. Consistent with the findings from studies of adult MGCT, gestational age was associated inversely with risk of MGCT, with a 70 to 75 percent reduction in risk for children born at term compared with those born pre-term. Parental, particularly maternal, self-reported exposure to chemicals or solvents (odds ratio [OR] = 4.6, 95 percent confidence interval [CI] = 1.9-11.3) and OR = 2.2, CI = 1.1-4.7 for maternal and paternal exposure, respectively) and plastic or resin fumes (OR = 12.0, CI = 1.9-75.0 [maternal] and OR = 2.5, CI = 1.0-6.5 [paternal]) were associated with elevated risk of MGCT. New findings, not reported previously, include a positive relationship of MGCT risk with birthweight and prolonged breastfeeding, an inverse association between MGCT risk and number of cigarettes smoked by the mother during pregnancy, and a 3.1-fold increased risk (CI = 1.5-6.6) associated with maternal urinary infections during index pregnancy. Although these findings need confirmation from future studies, they suggest a potential influence of in utero exposure to maternal endogenous hormones, parental environmental exposures, and maternal diseases during pregnancy in the development of childhood MGCT.

Adolescent↗

PubMed1995

Comparison of treatment regimens for pediatric lymphoblastic non-Hodgkin's lymphoma: a Childrens Cancer Group study.

PURPOSE: Patients with lymphoblastic non-Hodgkin's lymphoma (LB NHL) were randomized to treatment with either modified LSA2L2 or ADCOMP, which added daunorubicin (DAUN) and asparaginase (L-ASP) to the methotrexate (MTX), cyclophosphamide (CYT), vincristine (VCR), and prednisone (PRED) (COMP) regimen, in a clinical trial to determine the relative effectiveness and toxicity of the two regimens. PATIENTS AND METHODS: Patients with LB NHL were eligible for this randomized study if they were less than 22 years of age at diagnosis and had < or = 25% blasts in the bone marrow. Of 307 patients registered, 281 were fully eligible and assessable. Patients were stratified by extent of disease at diagnosis. RESULTS: The 5-year event-free survival (EFS) rate for patients with localized disease was 84%, and for patients with disseminated disease, 67%. There were four relapses in 28 patients with localized disease. Two hundred six patients had mediastinal primary tumors and despite local radiation, 34 of 63 failures in these patients involved the primary tumor site with or without other involvement. After adjusting for extent of disease at diagnosis, the regimens did not differ significantly with respect to risk for adverse events. The acute toxicity was primarily neutropenia and thrombocytopenia, with greater initial toxicity in patients on the LSA2L2 regimen. Three patients developed acute myelogenous leukemia. CONCLUSION: Long-term EFS in children with LB NHL can be achieved in the majority of patients. Disease progression, which includes recurrence at the primary tumor site, is a major cause of treatment failure in patients with mediastinal presentations. Addition of DAUN and L-ASP to the COMP regimen does not produce a more effective treatment than LSA2L2.

Adolescent↗

PubMed1994

A phase II study of carboplatin in children with recurrent or progressive solid tumors. A report from the Childrens Cancer Group.

BACKGROUND: Carboplatin is an analogue of cisplatin with less nonhematologic toxicity than the parent compound. It has been demonstrated previously to have activity against a spectrum of pediatric brain tumors. This Phase II study was undertaken to assess the activity of carboplatin in children with various solid tumors. METHODS: Between October 1985 and March 1988, the Childrens Cancer Group entered 117 patients with drug-resistant, recurrent lymphomas and solid tumors, excluding primary central nervous system tumors, into a Phase II trial of carboplatin given intravenously at a dosage of 560 mg/m2 over 1 hour every 4 weeks. RESULTS: A complete response was seen in 1 of 15 evaluable patients with Ewing's sarcoma. Partial responses were seen in 2 of 17 evaluable patients with neuroblastoma, 1 of 16 with soft tissue sarcoma, 2 of 5 with Wilms' tumor, and 1 with an endodermal sinus tumor of the testis. Objective responses were not seen in patients with malignant lymphoma, osteosarcoma, or hepatoma. Four of 7 patients who responded to carboplatin had previously received cisplatin. Sixty-two percent of patients had a platelet count nadir of less than 50,000/mm3, and 41% had an absolute neutrophil count nadir of less than 1,000/mm3. Ototoxicity, nephrotoxicity, hypomagnesemia, hypertransaminasemia, and nausea and vomiting each were seen in fewer than 10% of patients. CONCLUSIONS: Carboplatin has some activity against Wilms' tumor, Ewing's sarcoma, neuroblastoma, soft tissue sarcoma, and endodermal sinus tumor of the testis. Activity was not demonstrated against osteosarcoma, malignant lymphoma, hepatoma, and miscellaneous other tumors. Myelosuppression was seen commonly, and nonhematologic toxicity was infrequent.

Adolescent↗

PubMed1993

A phase I study of carboplatin in children with acute leukemia in bone marrow relapse. A report from the Childrens Cancer Group.

BACKGROUND: Carboplatin is an analogue of cisplatin with less nonhematologic toxicity and a similar spectrum of antineoplastic activity as the parent compound. Although cisplatin has not been found to be an active agent in leukemia, carboplatin induced complete remissions in adults with acute myelogenous leukemia (AML). Therefore, a pediatric Phase I study in acute leukemia was performed. METHODS: Between January 1988 and April 1990, the Childrens Cancer Group performed a Phase I study of carboplatin administered by a 5-day continuous intravenous infusion to children with acute leukemia in bone marrow relapse. RESULTS: Mild to moderate glomerular and tubular nephrotoxicity was seen in most patients treated at the initial dose level of 336 mg/m2/day. Therefore, patients at the second dose level were treated at 270 mg/m2/day. At this level, one patient died of acute hepatic necrosis and hepatic encephalopathy, and a second patient had presumed hemorrhagic cystitis develop. The third dose level tested, 216 mg/m2/day, was not associated with unacceptable toxic effects and was considered the maximum tolerated dose (dose-limiting toxicity was not observed). Within the confines of this Phase I study, antileukemic activity was shown in patients with acute lymphoblastic leukemia (ALL) and AML. CONCLUSIONS: In this pediatric Phase I trial of carboplatin in acute leukemia, glomerular and tubular nephrotoxicity was considered dose-limiting. In addition, hepatotoxicity and hemorrhagic cystitis were observed. Antileukemic activity was shown in patients with ALL and AML. The recommended Phase II dose is 216 mg/m2/day by 5-day continuous intravenous infusion.

Adolescent↗

PubMed1993

Trends in patterns of treatment of childhood cancer in Los Angeles County.

To assess the proportion of children with cancer who have been managed by mainstream pediatric cancer programs, population-based cancer incidence data for Los Angeles County (LAC) children (under 20 years of age) for the years 1972 through 1987 were linked with patient records of children registered with the two national cooperative pediatric oncology groups, Children's Cancer Study Group and Pediatric Oncology Group. The proportion of children with cancer who were registered by cooperative groups increased markedly over time: 9% of LAC children younger than 15 years of age who were diagnosed with cancer in 1972 were registered with cooperative groups, compared to 52% of those diagnosed in 1980 and 62% of those diagnosed in 1987. Registration rates decreased with increasing age at cancer diagnosis. In the most recent time period, 1984-1987, 66% of LAC children diagnosed with cancer under age 5 years were registered with cooperative groups compared to 62% of those who were 5 to 9 years old and 49% of those who were 10 to 14 years old; although they were frequently diagnosed with tumors considered to be childhood cancers, only 19% of older adolescents (aged 15-19 years) were registered. In LAC, there was no apparent bias in registration rates with regard to gender or racial-ethnic background. Among patients diagnosed in the period 1984-1987, children in the highest of five socioeconomic status categories were underrepresented among registrants. Registration rates were highest (70% or greater) for patients with acute lymphocytic and acute nonlymphocytic leukemia, medulloblastoma, hepatoblastoma, Wilms tumor, and rhabdomyosarcoma. Fewer than 50% of patients with other brain and central nervous system tumors, retinoblastoma, other soft tissue sarcomas, and bone tumors were registered with the cooperative groups.

Adolescent↗

PubMed1993

Patterns of enrollment on cooperative group studies. An analysis of trends from the Los Angeles County Cancer Surveillance Program.

To assess the proportion of children diagnosed with cancer who are enrolled on studies conducted by the two national pediatric cooperative groups, population-based cancer incidence data for Los Angeles county children younger than age 20 for the years 1980 through 1987 were linked with patient records of children registered with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG). For patients not enrolled on a protocol, demographic and disease characteristics were compared with summary eligibility requirements for CCG protocols that were open for enrollment during 1980-1987. The proportion of patients enrolled on studies conducted by the cooperative groups varied with tumor type and age at diagnosis. When patients younger than the age of 10 were diagnosed at an institution affiliated with one of the groups, the majority of those evaluated by our review as eligible for a study were enrolled on a protocol. The proportion of young patients entered on study among those whose diagnosis was not made at a cooperative group institution was generally smaller. Seventy-three percent of all potentially eligible patients with acute leukemia diagnosed between 1980-1987 were entered on a pediatric group protocol. Approximately 50% of all potentially eligible patients with brain tumors were entered on protocol. In contrast to this, less than 50% of patients older than the age of 14 and likely to be eligible for a study were entered on a pediatric group protocol, regardless of the tumor type. Indeed, bone tumors constituted the category of patients most likely to be enrolled, with 39% of all potentially eligible patients entered on a study in the period examined. If the patient's diagnosis was made at a cooperative group institution, the individual was more likely to be entered on a protocol than if the diagnosis was made at a center outside the cooperative group network. It was not possible to determine the precise reason for this trend from the data available. Some explanations include policies at cooperative group institutions regarding admission of patients older than age 14 and the availability of protocols from cooperative groups primarily focused on the treatment of cancers of adults.

Adolescent↗

PubMed1993

Treatment of pulmonary metastases of initial stage I hepatoblastoma in childhood. Report from the Childrens Cancer Group.

BACKGROUND: Hepatoblastoma is a difficult tumor to treat if not completely resected. Historically, the outlook has been dismal in children in whom recurrent disease has developed. To determine better treatments for recurrent hepatoblastoma, the experience of a recent Childrens Cancer Group study was reviewed. METHODS: Data were reviewed for all children with localized (Stage I) hepatoblastoma enrolled in the Childrens Cancer Group protocol CCG-881. Particular attention was paid to children with recurrent disease that included the lungs. Initial pathology slides, retreatments offered these patients, and patient survival were reviewed. RESULTS: In an initial group of 33 children with Stage I hepatoblastoma, there were 10 in whom recurrent disease developed. Six of these had pulmonary metastasis develop with or without other sites of recurrence. One of these six children had a very good partial response to retreatment with combination chemotherapy, but, overall, the most effective treatment modality was surgical resection of the pulmonary disease. Three children (of a total of 10 patients who had a recurrence at any site and 6 who had a recurrence that included the lung) are long-term disease-free survivors 64-104+ months after their most recent recurrence. CONCLUSIONS: Extended disease-free survival is possible for children with recurrent hepatoblastoma if the recurrence is isolated to the lung and an aggressive surgical approach with intent to cure is used.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group.

An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.

Adolescent↗

PubMed1992

13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group evaluated daily oral 13-cis-retinoic acid to determine its therapeutic efficacy in 28 children with advanced neuroblastoma refractory to conventional therapy. Cheilitis and fissured lips were the most common side effects; however, fewer than 50% of the patients experienced any toxicity. Two of twenty-two evaluable children demonstrated positive response to therapy. In one case, a child received the drug for 11 months. Seventeen patients demonstrated progressive disease within 28 days of the start of treatment. Three other patients with stable disease, or removed from study at day 28, were considered nonresponsive. Our data demonstrate that, when given as a single daily oral dose of 100 mg/m2, 13-cis-retinoic acid does not have significant activity in children with advanced neuroblastoma.

Adolescent↗