Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: a Pediatric Oncology Group study.

1994 ◽  
Vol 12 (8) ◽  
pp. 1616-1620 ◽  
Author(s):  
R P Castleberry ◽  
A B Cantor ◽  
A A Green ◽  
V Joshi ◽  
R L Berkow ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Pediatric Oncology ◽  
Phase Iii ◽  
Oncology Group ◽  
New Agents ◽  
Risk Of Death ◽  
Significant Difference ◽  
Pediatric Oncology Group ◽  
To Receive

PURPOSE Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. PATIENTS AND METHODS One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 i.v. over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 i.v. push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 i.v. on day 1, etoposide 200 mg/m2 i.v. on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 i.v. on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 i.v. on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. RESULTS After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. CONCLUSION IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

Lymphoblastic lymphoma in children--a randomized trial comparing LSA2-L2 with the A-COP+ therapeutic regimen: a Pediatric Oncology Group Study.

1988 ◽  
Vol 6 (1) ◽  
pp. 26-33 ◽  
Author(s):  
E V Hvizdala ◽  
C Berard ◽  
T Callihan ◽  
J Falletta ◽  
H Sabio ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Pediatric Oncology ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Lymphoblastic Lymphoma ◽  
Oncology Group ◽  
Treatment Regimens ◽  
Number Of Patients ◽  
Significant Difference ◽  
Pediatric Oncology Group

From May 1979 to March 1983, 76 evaluable patients with lymphoblastic lymphoma (LBL) were treated by members of the Pediatric Oncology Group (POG). Forty-six children treated by the six-drug A-COP+ regimen (Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], vincristine, prednisone, cyclophosphamide, methotrexate, and hydrocortisone) were compared in a prospective randomized trial with 30 patients receiving the modified ten-drug LSA2-L2 (cyclosphosphamide, vincristine, methotrexate, Daunomycin [daunorubicin cerubidine; Wyeth Laboratories, Philadelphia], prednisone, cytarabine, thioguanine, asparaginase, hydroxyurea, and carmustine) regimen. After adjusting for stage (I and II v III v IV), there was no statistically significant difference (P = .19) between A-COP+ and LSA2-L2 regimens on the basis of 3-year survival and disease-free survival (62% v 72% and 53% v 58%, respectively for the two treatment regimens) but the power of analysis and thus the ability to detect a clinically meaningful difference in the outcome with the two regimens was limited by the small number of patients. Neither therapy was effective for most patients with stage IV disease, with failure occurring in six of seven children receiving A-COP+ regimen and eight of 11 patients receiving LSA2-L2. Although the LSA2-L2 regimen was more toxic during the induction of remission, the toxicity during maintenance was acceptable and similar for both treatments. CNS relapse was not a significant problem whether cranial radiation with intrathecal (IT) therapy (A-COP+) or IT therapy alone (LSA2-L2) were used. Our results confirm the overall effectiveness of the LSA2-L2 regimen in children with LBLs, especially those initially free of bone marrow or CNS involvement, but were inconclusive as to the inferiority or superiority of this regimen over the A-COP+ regimen.

A Comparison of Hepatotoxicity and Neutropenia in Children Given Oral Mercaptopurine on a Twice-Daily Versus Once-Daily Dosing Schedule for Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 994-994
Author(s):  
R. Chesley ◽  
B. A. Bell ◽  
M. Devidas ◽  
B. Bostrom ◽  
G. Erdmann ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Oncology ◽  
Lymphoblastic Leukemia ◽  
Phase Iii ◽  
Oncology Group ◽  
Dose Frequency ◽  
Phase Dependence ◽  
Continuation Therapy ◽  
Pediatric Oncology Group ◽  
Grade 3

Abstract Pediatric Oncology Group (POG) protocol 9605, a phase III study of standard risk acute lymphoblastic leukemia (ALL), was designed in part to compare daily (QD) versus twice-daily (BID) mercaptopurine (MP) dosing during intensification and continuation therapy. 1082 patients were enrolled between 1996 and 1999. MP is an important antimetabolite in the treatment of ALL. Due to its S-phase dependence and short half-life, dosing frequency may be crucial to toxicity and/or efficacy. MP is converted into two major metabolites, 6-thioguanine (TGN) and 6-methylthioinosinic acid (mMP). Correlations of toxicity and dose frequency were tabulated. Red blood cell (RBC) TGN and mMP levels measured in a randomized subpopulation (226/1082 patients) on POG 9605 found markedly elevated mMP in the QD versus BID group (2020 versus 1275 ng/8x108 RBC) with slightly higher levels of TGN in the QD group (42 versus 40 ng/8x108 RBC). Toxicity events occurring during treatment were recorded according to toxicity code, grade and week of therapy. Toxicity events for 1037/1082 patients were analyzed. For each toxicity, QD and BID groups were compared based on total number of events, number of individual patients, and average number of events per patient. A comparison of the incidence of neutropenia and hepatotoxicity between QD and BID groups became the focus. 518/1037 patients received 6MP 75 mg/m2 daily and 519/1037 patients received 6MP 37.5 mg/m2 twice daily. Decreased ANC were coded as grade 3 (0.5–0.9 x 103/mm3) or grade 4 (less than 0.5 x 103/mm3). Decreased WBC were coded as grade 3 (1.0–1.9 x 103/mm3) or grade 4 (less than 1.0 x 103/mm3). Elevated aminotransferase (ALT/AST) were coded as grade 3 (5.1–20 x normal) or grade 4 (greater than 20 x normal). For grade 4 neutropenia, the QD group had a significantly higher average number of events per patient than the BID group (4.67 versus 4.22, p=0.021). Also for grade 3 ALT/AST, the QD group had a significantly higher average number of events per patient than the BID group (2.40 versus 2.10, p=0.046). In previous studies, higher mMP levels were found to be correlated with elevated aminotransferases. The subpopulation (n=226/1082) data was analyzed to compare metabolite levels in patients who experienced various toxicities. In the QD arm, TGN was significantly elevated in those patients with grades 3 and 4 WBC (p=0.026) and grades 3 and 4 ANC (p=0.032). MMP was significantly elevated in those with grades 3 and 4 WBC (p=0.0066), grades 3 and 4 ANC (p=0.009) and grades 3 and 4 ALT/AST (p=0.0082). QD administration of 6MP is associated with increased levels of methylated metabolites, elevated ALT/AST and decreased ANC. Neutropenia correlates with elevations of both TGN and mMP. Hepatotoxicity correlates with elevations in mMP. Issues of adherence to dosing may also play a role. Implications for patient outcome await data maturation.

Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study.

1998 ◽  
Vol 16 (5) ◽  
pp. 1723-1728 ◽  
Author(s):  
R K Mulhern ◽  
J L Kepner ◽  
P R Thomas ◽  
F D Armstrong ◽  
H S Friedman ◽  
...  
Keyword(s):  
Pediatric Oncology ◽  
Standard Dose ◽  
Cranial Irradiation ◽  
Oncology Group ◽  
Older Children ◽  
Reduced Dose ◽  
Related Quality ◽  
Pediatric Oncology Group ◽  
Performance Intelligence Quotient ◽  
To Receive

PURPOSE The purpose of this study was to test the hypothesis that survivors of medulloblastoma who were younger at diagnosis and those who received standard-dose cranial irradiation (SRT) of 36 Gy would have a lower performance on standardized tests of cognitive function and achievement than children who were older and those treated with reduced-dose cranial irradiation (RRT) of 23.4 Gy. PATIENTS AND METHODS Eligible patients had been treated on Pediatric Oncology Group (POG) study 8631 for low-risk medulloblastoma that randomized patients to receive RRT or SRT after surgical resection. Those who were alive and free of progressive disease 6.1 to 9.9 years from completion of treatment were eligible for this study. Of the 35 eligible patients, 22 patients (13 SRT, nine RRT) participated in a battery of tests that included intellectual and academic development as well as ratings of health-related quality of life. RESULTS Patients were stratified by treatment group (SRT v RRT) and into younger (Y) and older (O) groups by the median age at diagnosis (8.85 years), which resulted in four groups that we hypothesized would show neuropsychologic test scores in the following order: Y/SRT less than Y/RRT less than O/SRT less than O/RRT. Evidence to support the hypothesized ordering of groups in terms of neuropsychologic toxicity was obtained with regard to Performance Intelligence Quotient (IQ), Full Scale IQ, Attention, Reading, and Arithmetic. CONCLUSION Children treated for medulloblastoma experienced less severe neuropsychologic toxicity when treated with 23.4 Gy instead of 36 Gy cranial irradiation. Older children experienced less toxicity than children who were younger at the time of irradiation.

scholarly journals Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. A pediatric oncology group phase II study

Cancer ◽  
1993 ◽  
Vol 71 (5) ◽  
pp. 1898-1903 ◽  
Author(s):  
Faith H. Kung ◽  
Charles B. Pratt ◽  
Roger A. Vega ◽  
Norman Jaffe ◽  
Douglas Strother ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase Ii ◽  
Pediatric Oncology ◽  
Phase Ii Study ◽  
Oncology Group ◽  
Pediatric Oncology Group
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