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Journal of Clinical Oncology, Vol 22, No 14 (July 15), 2004: pp. 2885-2890
© 2004 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2004.09.073
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Treatment of Relapsed Wilms’ Tumor With High-Dose Therapy and Autologous Hematopoietic Stem-Cell Rescue: The Experience at Children’s Memorial Hospital

Andrew D. Campbell, Susan L. Cohn, Marleta Reynolds, Roopa Seshadri, Elaine Morgan, Grant Geissler, Alfred Rademaker, Maryann Marymount, John Kalapurakal, Paul R. Haut, Reggie Duerst, Morris Kletzel

From the Departments of Pediatrics, Surgery, Preventive Medicine, and Radiation Oncology and the Biometry Section, Northwestern University Feinberg School of Medicine, the Comprehensive Robert H. Lurie Cancer Center; and Children’s Memorial Hospital, Chicago, IL; University of Michigan; C.S. Motts Children’s Hospital, Ann Arbor, MI; Indiana University; and Riley Children’s Hospital, Indianapolis, IN

Address reprint requests to Morris Kletzel, MD, FAAP, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL 60614; e-mail: mkletzel{at}northwestern.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors’ Disclosures of...
 REFERENCES
 
PURPOSE: To investigate whether high-dose therapy with hematopoietic stem-cell rescue (HSCR) will improve survival for patients with relapsed Wilms’ tumor.

PATIENTS AND METHODS: Thirteen children with relapsed Wilms’ tumor were treated with one or two cycles of high-dose chemotherapy (HDT) followed by autologous HSCR. Twelve of 13 patients received reinduction chemotherapy before HDT and HSCR. The median age at diagnosis was 4.8 years, and the median time to relapse was 12 months. The histology was favorable in 12 of 13 patients. The ablative regimens included: (1) thiotepa (TT)/cyclophosphamide (CTX)/carboplatin (CP; n = 2); (2) TT/CTX (n = 5); (3) TT/etoposide (ETP; n = 1); and (4) CP/ETP/CTX (n = 1). Four patients received two cycles of HDT and HSCR. Cycle 1 consisted of CP/ETP/CTX, and melphalan/CTX were used in cycle 2.

RESULTS: Seven of 13 patients are alive without evidence of disease, with a median follow-up of 30 months. The 4-year estimated event-free survival (EFS) rate is 60% (95% CI, 0.40 to 6.88), and the overall survival (OS) at 4 years is 73% (95% CI, 0.40 to 6.86). There was no transplant-related mortality. All patients engrafted to an absolute neutrophil count 500/µL at a median of 13 days (range, 8 to 62 days) and had an unsustained platelet count > 20.0µ at a median of 16 days (range, 10 to 202 days).

CONCLUSION: Our results suggest that HDT with HSCR is an effective treatment for patients with Wilms’ tumor who experience relapse.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors’ Disclosures of...
 REFERENCES
 
Wilms’ tumor is highly sensitive to chemotherapy and radiation, and refinements in surgery, chemotherapy, and radiation therapy have led to cure rates that exceed 85%.1 However, even with modern multimodality treatment, approximately 10% to 15% of patients with favorable-histology disease and 50% of patients with anaplastic tumors experience tumor progression or relapse. Outcome remains poor for this subset of patients with relapse. In the second and third National Wilms’ Tumor Studies (NWTS), the 3-year postrelapse survival rate was only 30% ± 3% for patients who received initial treatment with surgery, radiotherapy, and a three-drug chemotherapy regimen of dactinomycin, vincristine, and doxorubicin.2 Similar to newly diagnosed Wilms’ tumors, relapsed Wilms’ tumors are clinically heterogeneous, and subgroups of patients with relapse identified in the NTWS-2 and -3 trials had 3-year postrelapse survival rates of > 40%. Factors shown to be predictive of a more favorable prognosis after recurrence included favorable histology, initial treatment with only vincristine and dactinomycin, relapse to the lungs only, relapse in the abdomen when radiotherapy was not initially given, and relapse more than 12 months after diagnosis.

In an effort to improve survival rates for relapsed Wilms’ tumor patients, more intensive treatment strategies have recently been used. Response rates ranging from 42% to 73% have been reported with ifosfamide-, platinum-, and etoposide-containing regimens.3-8 Several groups have recently treated patients experiencing relapse with high-dose chemotherapy (HDT) followed by autologous hematopoietic stem-cell rescue (HSCR).9-17 Although only small numbers of patients have undergone HDT plus HSCR, promising survival rates, ranging from 32% to 60%, have been reported.9,11,15,17 Between 1991 and 2001, we treated 13 children with relapsed Wilms’ tumor with HDT and HSCR at Children’s Memorial Hospital in Chicago. Our results indicate that HDT and HSCR is an effective treatment for relapsed Wilms’ tumor.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 Authors’ Disclosures of...
 REFERENCES
 
From December 1991 to June 2001, 103 patients were diagnosed with Wilms’ tumor at Children’s Memorial Hospital. Eleven of these children experienced relapse and were treated on institutional stem-cell transplant studies. An additional two patients with relapse, who had received initial treatment elsewhere, were referred to our institution and enrolled onto our transplant study. The treatment protocols were approved by the institutional review board at Children’s Memorial Hospital, and signed informed consent was obtained for all patients.

Reinduction Chemotherapy
Following disease relapse, 12 patients were treated with reinduction chemotherapy. Seven patients were treated with cyclophosphamide 14.7 mg/kg/d x 5 days or 500 mg/m2 x 4 days, etoposide 3.3 mg/kg/d x 5 days or 100 mg/m2 x 5 days, and carboplatin 16.7 mg/kg/d x 5 days or 500 mg/m2 x 3 days. The remaining patients received ifosfamide 1.8gm/m2/d x 5 days, carboplatin 400 mg/m2/d x 2 days, and etoposide 100 mg/m2/d x 5 days (ICE; n = 2); cyclophosphamide 400 mg/m2/d x 5 days and etoposide 100 mg/m2/d x 5 days (n = 1); ICE plus doxorubicin 30 mg/m2/d x 2 days (n = 1); or vincristine 0.05 mg/kg/d x 1 day, doxorubicin 1.5 mg/kg/d x 1 day, cyclophosphamide 14.7 mg/kg x 5 days, and etoposide 3.3 mg/kg/d x 5 days (n = 1). One patient did not undergo reinduction therapy before consolidation with HDT and HSCR.

Hematopoietic Stem-Cell Mobilization and Collection
HSCs were collected through a double-lumen central venous line after mobilization with either granulocyte colony-stimulating factor 5 to 10 µg/kg/daily x 4 days (n = 11) or granulocyte-macrophage colony-stimulating factor 250 µg/m2 daily x 4 days (n = 2). The collection was performed on day 5 with a COBE Spectrapheresis machine (Gambro BCT, Lakewood, CO). Twelve patients underwent HSC harvests after two cycles of chemotherapy, regardless of their disease status. The single patient who did not received reinduction therapy had stem cells harvested with granulocyte colony-stimulating factor mobilization 2 weeks before his transplant. Cells were transported to the stem-cell lab for cell count, culture, and cryopreservation according to our institutional procedures. Four to five blood volumes were processed for each collection. The median mononuclear cell count and CD34+ cells collected on the patients who underwent a single transplant were 2.5 x 108 per kg (range, 0.66 x 108 to 3.7 x 108 cells per kg) and 1.16 x 106 per kg (range, 0.75 x 108 to 3.6 x 108 cells per kg), respectively. For the patients who underwent two rescues, the median mononuclear cells collected was 2.3 x108 per kg for the first rescue and 1.5 x 106 per kg CD34+ cells for the second rescue; the collected cells were divided equally in two aliquots for these patients. The median weight of the patients was 19.7 kg (range, 11 to 61 kg); the median volume collected was 141 mL (range, 100 to 700 mL). The day of infusion, cells were transported to the designated area and infused via central venous line after urine alkalinization was achieved.

High-Dose Chemotherapy
Six patients received ablation with thiotepa 300 mg/m2/d from day –7 to –5, followed by cyclophosphamide 1,500 mg/m2/d from day –5 to –2; in two patients, carboplatinum at a dose of 667 mg/m2 on days –3 and –2 was added. For one patient, cyclophosphamide was substituted with etoposide 800 mg/m2 on days –4 and –3 (because of a history of severe hemorrhagic cystitis). The remaining four patients received two cycles of high-dose chemotherapy because of an institutional change in the protocol. Cycle 1 consisted of carboplatinum 667 mg/m2/d on days –6 to –4, etoposide 800 mg/m2/d on days –6 to –4, and cyclophosphamide 1.8 mg/m2/d on days –3 and –2, and the second cycle of high-dose chemotherapy contained melphalan 60 mg/m2/d days –8 to –6 and cyclophosphamide 1.5 mg/m2/d on days –5 to –2. Cells were infused on day 0.

Statistical Analysis
The Kaplan-Meier method was used to estimate 4-year overall survival (OS) and event-free survival (EFS) rates. OS and EFS functions were compared by the log-rank test. The cutoff date for the analyses was December 1, 2003. Engraftment of WBC and platelets are presented in a reverse Kaplan-Meier plot.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 Authors’ Disclosures of...
 REFERENCES
 
Patient Characteristics
The clinical characteristics of the 13 patients in this cohort are summarized in Table 1. The median age at diagnosis was 4.8 years (range, 12 months to 15 years). At the time of diagnosis, five patients had stage IV disease, five had stage III, one had stage II, and two had stage I disease. Tumor histology was favorable in 12 of 13 patients. The single patient with unfavorable histology Wilms’ tumor had diffuse anaplasia. All patients initially underwent nephrectomy. The 10 patients with stage III or IV Wilms’ tumor received 24 weeks of vincristine, actinomycin-D, and doxorubicin on study, according to the NWTS IV (regimen DD4A)18 or NWTS V (regimen DD4A). The three patients with stages I (n = 2) or II (n = 1) disease received vincristine and actinomycin-D for 18 weeks, according to the NWTS V study (regimen EE-4A).19 Ten patients also received radiation therapy to their primary site of disease as part of their initial treatment. Radiation to the lungs was given in two patients with stage IV disease (patients 1 and 3) and to epidural sites in two patients with spinal disease (patients 3 and 5). One patient (patient 11) underwent second-look surgery to remove tumor in intra-atrial and venal caval sites. The median time to relapse after diagnosis was 12 months (range, 2 to 19 months; Tables 2 and 3). The lungs and pelvis were the most common sites of relapse (n = 5), followed by the liver (n = 4). Two patients developed intraspinal recurrent disease. At the time of relapse, 12 of the 13 patients had at least one unfavorable prognostic characteristic, according to the criteria described by Grundy et al.2 Nine patients experienced relapse ≤ 12 months from diagnosis; five of these patients experienced relapse within 6 months of initial diagnosis. One patient had unfavorable histology. Six patients experienced abdominal relapse after receiving abdominal radiation, and 10 of the 13 patients initially received three-drug chemotherapy.


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  		Table 1. Patient Characteristics and Initial Treatment

 

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  		Table 2. Characteristics of Patients Treated With a Single Cycle of HDT and HSCR

 

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  		Table 3. Characteristic of Patients Treated With Two Cycles of HDT and HSCR

 
Treatment of Relapsed Disease
Twelve of 13 patients received cytoreductive reinduction chemotherapy before HDT plus HSCR (Table 2). Stem cells were harvested following the second cycle of reinduction chemotherapy (n = 12) or before transplant (n = 1). Radiation treatment to the lungs (120 Gy) abdomen (105 to 108 Gy), or epidural relapse site (150 Gy) was given before HDT and HSCR in four patients. Surgical resection was performed in three patients before HDT plus HSCR—one patient with a residual pelvic mass and two patients with liver masses. Seven patients achieved a complete remission (CR) before HDT and HSCR, and six achieved a partial remission (PR). All 13 patients underwent consolidation therapy consisting of either a single cycle of HDT and HSCR (n = 9) or two cycles of HDT and HSCR (n = 4; Tables 2 and 3).

Engraftment and HDT-Related Toxicities
Engraftment occurred in all patients regardless of whether they received one or two cycles of HDT plus HSCR. Following the HDT, each patient received a median of 2.5 x 108 mononuclear cells per kg (range, 0.66 to 3.8 cells), and a median 1.1 x 106 CD34+ cells per kg (range, 0.75 x 106 to 36.0 x 106 cells). An ANC > 500/µL and a platelet count of > 20,000/µL without transfusion were achieved at a median of 13 days (range, 8 to 62 days; mean,18.7 days) and 16 days (range, 10 to 202 days; mean, 41 days), respectively (Fig 1). Patient 5 had delayed engraftment of neutrophils and platelets. An etiology for the delayed engraftment was not identified. Toxicities included: grade 1-2 mucositis and fever with neutropenia (n = 13); bacteremia (n = 4); and renal tubular acidosis (n = 2). One patient had an infection with herpes zoster on day +31, and one patient developed chronic osteopenia.



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  		Fig 1. Reverse Kaplan-Meier plot of time to engraftment to an absolute neutrophil count > 500/µL and platelet count > 20/µL.

 
Outcome
Seven of the 13 patients remain disease-free, with a median follow-up of 30 months (range, 7 months to 10 years). The estimated 4-year EFS is 60% (95% CI, 0.40 to 6.88) and the 4-year OS rate is 73% (95% CI, 0.40 to 6.863; Fig 2). Six patients were in CR before undergoing HDT. Five of these six patients remain alive with no evidence of disease with follow-up ranging from 13+ to 144+ months. Two of the seven patients (patients 6 and 8) developed and died after undergoing HDT and HSCR (Tables 2 and 3). Patient 6 died 4 months after completing the HDT plus HSCR. Patient 8, the single patient in this cohort with unfavorable histology (diffuse anaplasia), died of disease 9 months after consolidation therapy. Of the six patients in PR at the time of first HDT and HSCR, one remains disease-free (patient 10). Interestingly, patient 10 underwent two cycles of HDT and HSCR and was in CR before the second cycle of HDT. The other four patients in PR before starting consolidation therapy relapsed (Patients 3, 11, 12, and 13). Patient 3 died from progressive disease 7 months following HDT and HSCR. Patient 11 experienced relapse in the brain 16 months after second transplant. Following radiation therapy to the brain and chemotherapy, this patient remains in CR 5 months after radiation to the brain. Patient 12 also experienced relapse after her first stem-cell transplant in the primary site. This patient was due to receive two HSCRs, but because of parental refusal received only one HSCR; this patient is still alive and receiving chemotherapy. Patient 13 also received two cycles of HDT and HSCR; he subsequently experienced recurrence in the abdomen outside the radiation field 7 months after transplant. This patient is currently alive with disease 12 months following consolidation therapy on a phase 2 treatment protocol.



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  		Fig 2. Kaplan-Meier analysis event-free survival (EFS) and overall survival (OS) of 13 patients with relapsed Wilms’ tumor from the time of high-dose chemotherapy and hematopoietic stem cell rescue.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
Authors’ Disclosures of...
 REFERENCES
 
Relapsed Wilms’ tumor is clinically heterogeneous, and some patients can be effectively treated with standard dose chemotherapy and radiation. However, outcome remains poor for the subset of patients with adverse prognostic features, including unfavorable histology, relapse less than 12 months from diagnosis, and initial treatment with the three-drug chemotherapy.2 More effective therapy is desperately needed for this high-risk group of patients. In this study, we treated 13 children with relapsed Wilms’ tumor with HDT and HSCR. Twelve of the 13 patients in our study cohort had at least one of the described unfavorable prognostic factors.2 Nine of the patients experienced relapse ≤ 12 months after initial diagnosis, and 10 of the 13 patients were initially treated with vincristine, dactinomycin, and doxorubicin. Nine of the patients received a single cycle of HDT and HSCR, and four underwent two cycles of HDT plus HSCR. Five children were in CR at the time of consolidation, and six were in PR. With a median follow-up of 25 months, the estimated 4-year EFS and OS rates are 60% and 73%, respectively. Thus, our results suggest that HDT and HSCR may be an effective treatment strategy for patients with Wilms’ tumor who experience replase and who have high-risk features. It is not certain that those patients with early stage disease at diagnosis, who receive two drugs initially may have benefited from HSCT. We can argue that these patients have some of the risk factors described earlier at the time of relapse.

Recently, Abu-Ghosh et al3 reported a 3-year EFS rate of 63% in 11 patients with high-risk relapsed Wilms’ tumor following treatment with ifosfamide, carboplatin, and etoposide. Others have described promising results following treatment with HDT and HSCR. The French Society of Pediatric Oncology reported EFS and OS rates of 50% and 60%, respectively, following treatment with an ablative regimen of melphalan, etoposide, and carboplatin and HSCR. Recently, the European Bone Marrow Transplant Registry (EBMTR) reported the outcome of 17 children with relapsed Wilms’ tumor patients treated with a number of different myeloablative regimens including high-dose etoposide, etoposide with carboplatin, melphalan, and melphalan with vincristine.9 The EFS rate for this cohort was 34%, with eight patients given transplants in CR disease-free 14 to 90 months following HDT and HSCR. The German Cooperative Wilms’ Tumor Study Group treated 20 Wilms’ patients experiencing relapse with melphalan, etoposide, and carboplatin, along with HSCR. Fourteen of these patients remained disease-free 37 to 116 months after autologous HSCR.17 Etoposide, carboplatin, and cyclophosphamide followed by autologous HSCR has also been reported to be effective treatment in a single patient with multiple-relapsed Wilms’ tumor.15

The clinical efficacy of two cycles of high-dose chemotherapy with HSCR in relapsed Wilms’ tumor was first described in a case report by Maurer et al13 in 1997. The first ablative regimen consisted of high-dose melphalan, etoposide, and carboplatin, and the second consisted of cyclophosphamide and etoposide.

In our series, no increase in toxicity was observed in the patients who underwent two versus one cycle of HDT and HSCR. Three of four patients who received the double transplant regimen were in PR before the first cycle of HDT and HSCR. All three patients responded to the first cycle of therapy and achieved a CR before undergoing the second cycle of therapy with HSCR. One of these patients has remained disease-free for 31+ months. Previous studies indicate that patients in CR at the time of HDT and HSCR have better outcomes than those with active disease.9,17 Thus, for patients who are not able to achieve a CR with standard-dose therapy, tandem cycles of HDT with HSCR may confer a survival advantage.

The heterogeneous nature of relapsed Wilms’ tumor and the small numbers of patients who develop recurrent disease make it difficult to determine which treatment strategy is optimal. For patients with favorable prognostic features, standard-dose chemotherapy may be curative. Our results, as well as those from the French and German groups, suggest that treatment with HDT followed by autologous HSCR is effective in high-risk relapsed Wilms’ tumor patients. North American and European cooperative groups should consider developing an international relapsed Wilms’ tumor study to prospectively compare different treatment regimens so that therapy can be optimized and survival improved.


   Authors’ Disclosures of Potential Conflicts of Interest
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors’ Disclosures of...
REFERENCES
 
The authors indicated no potential conflicts of interest.


   NOTES
 
Authors’ disclosures of potential conflicts of interest are found at the end of this article.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 Authors’ Disclosures of...
 REFERENCES
 
1. Green DM, Thomas PR, Schochats S, et al: The treatment of Wilms’ tumor: Results of the National Wilms’ Tumor Studies. Hematol Oncol Clin North Am 9:1267-1274, 1995[Medline]

2. Grundy P, Breslow N, Green DM, et al: Prognostic factors for children with recurrent Wilms’ Tumor: Results from the Second and Third National Wilms’ Tumor Study. J Clin Oncol 7:638-647, 1989[Abstract]

3. Abu-Ghosh AM, Krailo MD, Goldman SC, et al: Ifosfamide, carboplatin, and etoposide in children with poor-risk relapsed Wilms’ tumor: A Children’s Cancer Group report. Ann Oncol 13:460-469, 2002[Abstract/Free Full Text]

4. Kung FH, Berstein ML, Camitta BM, et al: Ifosfamide/carboplatin/etoposide (ICE) in the treatment of advanced, recurrent Wilms’ tumor. Proc Am Soc Clin Oncol 17:2156, 1999 (abstr 2156)

5. Pein F, Tournade MF, Zucker JM, et al: Etoposide and carboplatin: Highly effective combination in relapsed or refractory Wilms’ tumor—A phase II study by the French Society of Pediatric Oncology. J Clin Oncol 12:931-936, 1994[Abstract/Free Full Text]

6. De Camargo B, Melargno R, Saba e Silva N, et al: Phase II study of carboplatin as a single drug for relapsed Wilms’ tumor: Experience of the Brazilian Wilms’ Tumor Study Group. Med Pediatr Oncol 22:258-260, 1994[Medline]

7. Malogolowkin M, Feusner J, Steele DA, et al: Carboplatin/etoposide for the treatment of children with high risk or recurrent Wilms’ tumor. Proc Am Soc Clin Oncol 13:424, 1994 (abstr)

8. Miser J, Krailo M, Hammond GD, et al: The combination of ifosfamide, etoposide, and MESNA: A very active regimen in the treatment of recurrent Wilms’ tumor. Proc Am Soc Clin Oncol 12:417, 1993 (abstr)

9. Garaventa A, Hartmann O, Benard JL, et al: Autologous bone marrow transplantation for pediatric Wilms’ tumor: The experience of the European Bone Marrow Transplantation Solid Tumor Registry. Med Pediatr Oncol 22:11-14, 1994[Medline]

10. Kletzel M, Morgan E, Cohn SL, et al: Autologous bone marrow (BM)/peripheral blood stem cell rescue in children with relapsed Wilms’ tumor (WT). Proc Am Soc Clin Oncol 12:414, 1993 (abstr 1451)

11. Pein F, Michon J, Valteau-Couanet D, et al: High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms’ tumor: A French Society of Pediatric Oncology Study. J Clin Oncol 16:3295-3301, 1998[Abstract]

12. Saarinen-Pihkala UM, Wikstrom S, Vettenranta K, et al: Maximal preservation of renal function in patients with bilateral Wilms’ tumor: Therapeutic strategy of late kidney-sparing surgery and replacement of radiotherapy by high-dose melphalan and stem cell rescue. Bone Marrow Transplant 22:53-59, 1998[CrossRef][Medline]

13. Maurer K, Heitger A, Schwaighofer H, et al: Double high-dose chemotherapy with autologous peripheral stem cell rescue in relapsed Wilms’ tumor. Bone Marrow Transplant 20:1111-1113, 1997[CrossRef][Medline]

14. Perentesis JP, Katsanis E, DeFor TE, et al: Autologous stem cell transplantation for high-risk pediatric solid tumors. Bone Marrow Transplant 24:609-615, 1999[CrossRef][Medline]

15. Dagher R, Kreissman S, Robertson K, et al: High dose chemotherapy with autologous peripheral blood progenitor cell transplantation in an anephric child with multiply recurrent Wilms’ tumor. J Pediatr Hematol Oncol 20:357-360, 1998[CrossRef][Medline]

16. Kletzel M, Kim AR: Autologous bone marrow transplantation in pediatric solid tumors. Blood Stem Cell Transplant 334-351, 1997

17. Kremens B, Gruhn B, Klingebiel T, et al: High-dose chemotherapy with autologous stem rescue in children with nephroblastoma. Bone Marrow Transplant 30:893-898, 2002[CrossRef][Medline]

18. Malogolowkin M, Bergman T, Seibel N, et al: Outcome and prognostic factors for patients with recurrent Wilms’ tumor: National Wilms’ Tumor Study 3 and 4. Proc Am Soc Clin Oncol 19:3236, 2001 (abstr 3136)

19. Green DM, Breslow NE, Beckwith JB, et al: 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. J Clin Oncol 16:237-245, 1998[Abstract/Free Full Text]

Submitted September 12, 2003; accepted April 23, 2004.


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