Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

1998 ◽  
Vol 16 (12) ◽  
pp. 3744-3751 ◽  
Author(s):  
D M Green ◽  
N E Breslow ◽  
J B Beckwith ◽  
J Z Finklestein ◽  
P Grundy ◽  
...  
Keyword(s):  
Single Dose ◽  
Divided Dose ◽  
Wilms Tumor ◽  
Clear Cell Sarcoma ◽  
Duration Of Treatment ◽  
Total Treatment Cost ◽  
Administration Schedule ◽  
Treatment Regimens ◽  
Favorable Histology ◽  
Tumor Study

PURPOSE National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.

1998 ◽  
Vol 16 (1) ◽  
pp. 237-245 ◽  
Author(s):  
D M Green ◽  
N E Breslow ◽  
J B Beckwith ◽  
J Z Finklestein ◽  
P E Grundy ◽  
...  
Keyword(s):  
Single Dose ◽  
Divided Dose ◽  
Clear Cell ◽  
Wilms Tumor ◽  
Dose Intensity ◽  
Clear Cell Sarcoma ◽  
Hematologic Toxicity ◽  
Cell Sarcoma ◽  
Favorable Histology ◽  
Tumor Study

PURPOSE The National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS Between August 6, 1986 and September 1, 1994, 1,687 previously untreated children less than 16 years of age with stages I to II/favorable histology (FH) or stage I/anaplastic histology WT (low-risk [LR] group) or stages III to IV/FH WT or stages I to IV/clear cell sarcoma of the kidney (high-risk [HR] group) were randomized to treatment that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either STD courses (3 days) or PI treatment with doxorubicin. RESULTS The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to treatment with STD chemotherapy (P = .988). The 2-year RFS rates for HR patients were 87.3% for 299 randomized to treatment with PI and 90.0% for 288 randomized to treatment with STD chemotherapy (P = .865). CONCLUSION We conclude that patients treated with PI combination chemotherapy for LR or HR WT or clear cell sarcoma of the kidney have equivalent 2-year RFS to those treated with STD regimens. PI drug administration is recommended as the new standard based on demonstrated efficacy, greater administered dose-intensity, less severe hematologic toxicity, and the requirement for fewer physician and hospital encounters.

Effect of Duration of Treatment on Treatment Outcome for Patients With Clear-Cell Sarcoma of the Kidney: A Report From the National Wilms' Tumor Study Group

2004 ◽  
Vol 22 (3) ◽  
pp. 468-473 ◽  
Author(s):  
Nita L. Seibel ◽  
Sierra Li ◽  
Norman E. Breslow ◽  
J. Bruce Beckwith ◽  
Daniel M. Green ◽  
...  
Keyword(s):  
Overall Survival ◽  
Single Dose ◽  
Divided Dose ◽  
Clear Cell ◽  
Wilms Tumor ◽  
Survival Rates ◽  
Clear Cell Sarcoma ◽  
Cell Sarcoma ◽  
Tumor Study ◽  
Overall Survival Rates

Purpose To evaluate the effect of conventional and standard (ST) versus pulse-intensive (PI) chemotherapy and short-duration versus long-duration chemotherapy on relapse-free survival (RFS) and overall survival rates of patients with clear-cell sarcoma of the kidney (CCSK) entered onto the National Wilms' Tumor Study (NWTS)-4. Patients and Methods The 5-year and 8-year RFS rates were determined for patients with CCSK treated on the NWTS-4. After August 6, 1986, 40 previously untreated children younger than 16 years with CCSK were randomly assigned, after the completion of 6 months of chemotherapy, to discontinue (short) or continue 9 additional months (long) of treatment with chemotherapy regimens that included vincristine and either divided-dose (ST) courses (5 days) or single-dose (PI) treatment with dactinomycin and divided-dose (ST) courses (3 days) or single-dose (PI) treatment with doxorubicin. Results For patients with CCSK, the 5- and 8-year RFS rates were 65.2% and 60.6%, respectively, for patients randomly assigned to the short chemotherapy and 87.8% (both 5- and 8-year RFS) for patients randomly assigned to the long chemotherapy (P = .08). The overall survival rates for patients at 5 and 8 years were 95.5% and 85.9%, respectively, for the short chemotherapy and 87.5% (both 5- and 8-year overall survival) for the long chemotherapy (P = .99). In NWTS-4, the overall survival rates for patients with CCSK improved from NWTS-3 (83% v 66.9% at 8 years, respectively; P < .01). Conclusion CCSK patients exhibit an improved RFS from a longer course of therapy when using vincristine, doxorubicin, and dactinomycin, but their long-term survival is unchanged compared with patients receiving 6 months of therapy. The overall survival rates for patients with CCSK have improved from NWTS-3.

Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study.

1990 ◽  
Vol 8 (9) ◽  
pp. 1525-1530 ◽  
Author(s):  
D M Green ◽  
P Norkool ◽  
N E Breslow ◽  
J Z Finklestein ◽  
G J D'Angio
Keyword(s):  
Single Dose ◽  
Divided Dose ◽  
Wilms Tumor ◽  
Dose Schedule ◽  
Hepatic Toxicity ◽  
Anesthetic Agents ◽  
Tumor Study ◽  
Relationship Of ◽  
The Relationship ◽  
Control Study

To evaluate the effect of dactinomycin (AMD) dose and schedule on the frequency of severe hepatic toxicity in unirradiated National Wilms' Tumor Study-4 (NWTS-4) patients, we reviewed the records of 154 children randomized to single-dose AMD and 176 children randomized to divided-dose AMD administration. All the children also received vincristine in identical dose schedules for the first 10 weeks. The frequency of severe hepatic toxicity encountered in the early weeks of therapy was 14.3% (five of 35) among patients treated with 60 micrograms/kg of AMD, 3.7% (four of 108) among patients given 45 micrograms/kg, and 2.8% (five of 176) among patients treated with 15 micrograms/kg per dose times five doses (P = .025). The data suggest an increased frequency of severe hepatic toxicity with the higher, single-dose schedule of administration. However, the frequency of severe hepatic toxicity among the patients in the two remaining groups is markedly higher than the 0.4% observed among similar unirradiated patients in NWTS-3. The relationship of this toxicity to factors such as anesthetic agents, blood transfusions, intercurrent viral infection, or other presently unrecognized causes can be further evaluated only with a detailed investigation such as a case-control study.

Loss of Heterozygosity for Chromosomes 1p and 16q Is an Adverse Prognostic Factor in Favorable-Histology Wilms Tumor: A Report From the National Wilms Tumor Study Group

2005 ◽  
Vol 23 (29) ◽  
pp. 7312-7321 ◽  
Author(s):  
Paul E. Grundy ◽  
Norman E. Breslow ◽  
Sierra Li ◽  
Elizabeth Perlman ◽  
J. Bruce Beckwith ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Loss Of Heterozygosity ◽  
Wilms Tumor ◽  
Clear Cell Sarcoma ◽  
Stage I ◽  
Disease Stage ◽  
Malignant Rhabdoid Tumor ◽  
Favorable Histology ◽  
Tumor Study ◽  
Increased Risk

Purpose To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.

Treatment of Anaplastic Histology Wilms' Tumor: Results From the Fifth National Wilms' Tumor Study

2006 ◽  
Vol 24 (15) ◽  
pp. 2352-2358 ◽  
Author(s):  
Jeffrey S. Dome ◽  
Cecilia A. Cotton ◽  
Elizabeth J. Perlman ◽  
Norman E. Breslow ◽  
John A. Kalapurakal ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Treatment Strategies ◽  
Stage I ◽  
Event Free Survival ◽  
Free Survival ◽  
Treatment Regimens ◽  
Favorable Histology ◽  
Tumor Study ◽  
Anaplastic Histology ◽  
Novel Treatment Strategies

Purpose An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH). Patients and Methods Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation. Results A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively. Conclusion The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.

Treatment outcomes in patients less than 2 years of age with small, stage I, favorable-histology Wilms' tumors: a report from the National Wilms' Tumor Study.

1993 ◽  
Vol 11 (1) ◽  
pp. 91-95 ◽  
Author(s):  
D M Green ◽  
N E Breslow ◽  
J B Beckwith ◽  
J Takashima ◽  
P Kelalis ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Stage I ◽  
P Value ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Treatment Regimens ◽  
Survival Percentage ◽  
Favorable Histology ◽  
Specimen Weight ◽  
Tumor Studies

PURPOSE Retrospective analyses were performed to determine the effect of tumor weight and therapy modifications on outcome in patients less than 2 years of age with stage I favorable-histology Wilms' tumors. PATIENTS AND METHODS The 4-year relapse-free and overall survival percentages for patients randomized to different treatment regimens in National Wilms' Tumor Studies (NWTS)-1, -2, and -3 were calculated and compared. RESULTS The 4-year relapse-free survival percentages of patients whose specimen weight was less than 550 g were found to be 89.1% on NWTS-1, 96.0% on NWTS-2, and 93.2% on NWTS-3. There was no evidence that the relapse-free survival of these patients had improved over time (P value for trend = .99). The 4-year relapse-free survival percentage for similar age and stage patients whose specimen weight was 550 g or greater was significantly poorer than that of patients with smaller tumors (P = .02). CONCLUSION Changes in the NWTS treatment regimens over a period of more than 20 years have not improved on the excellent prognosis of patients who are less than 2 years of age at diagnosis and who have a stage I, favorable-histology Wilms' tumor with specimen weight less than 550 g. These data could be used as the basis for a future trial in which a subgroup of such patients is treated with nephrectomy only.

Outcomes in low-risk babies treated with half-dose chemotherapy according to the Third National Wilms' Tumor Study.

1992 ◽  
Vol 10 (8) ◽  
pp. 1305-1309 ◽  
Author(s):  
B W Corn ◽  
J W Goldwein ◽  
I Evans ◽  
G J D'Angio
Keyword(s):  
Wilms Tumor ◽  
Survival Rates ◽  
Chemotherapeutic Agents ◽  
Low Risk ◽  
Hematologic Toxicity ◽  
Older Children ◽  
The Third ◽  
Favorable Histology ◽  
Tumor Study ◽  
Half Dose

PURPOSE To determine whether the 50% dose reduction of all chemotherapeutic agents recommended for babies (less than or equal to 12 months of age) by the Third National Wilms' Tumor Study (NWTS-3) produced acceptable toxicity without sacrificing any survival benefit. MATERIALS AND METHODS The 365 babies enrolled in NWTS-3 had tumors of varying histologies and stages. The present analysis was restricted to the 256 infants who had tumors of favorable histology, were free of metastasis at diagnosis, and received treatment according to NWTS-3 guidelines. RESULTS Despite the recommended attenuation of drug doses observed in 75% of the chemotherapy courses received, outcomes for these babies were comparable to those obtained in older children given full doses of chemotherapy. Four-year survival rates for 256 babies with stages I (n = 199), II (n = 38), and III (n = 19) favorable-histology tumors were 96%, 95%, and 90%, respectively. The figures for 498 stage I, 342 stage II, and 373 stage III older children with favorable-histology lesions were 92%, 94%, and 91% in that order. There were no deaths from hematologic toxicity or infection among babies who received half-dose chemotherapy. The death rates for their older NWTS-3 counterparts was 1%. CONCLUSION Less aggressive therapies advocated for babies in NWTS-3 provide acceptable levels of morbidity without compromising the excellent results previously reported for low-risk patients of all ages.

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