Wilms tumor

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 Elaine Fan, MD
KU School of Medicine
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3 regimens on this page
3 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

NCCN

Neoadjuvant therapy

Vincristine monotherapy

Regimen

Study Evidence
Sullivan et al. 1967 Pilot

Chemotherapy

Subsequent treatment

References

  1. Sullivan MP, Sutow WW, Cangir A, Taylor G. Vincristine sulfate in management of Wilms' tumor: replacement of preoperative irradiation by chemotherapy. JAMA. 1967 Oct 30;202(5):381-4. link to original article PubMed
  2. NWTS-1: D'Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, Goodwin W, Leape LL, Sinks LF, Sutow W, Tefft M, Wolff J. The treatment of Wilms' tumor: Results of the national Wilms' tumor study. Cancer. 1976 Aug;38(2):633-46. link to original article PubMed

Adjuvant therapy

Dactinomycin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Wolff et al. 1968 1964-NR Randomized (E-esc) Dactinomycin x 1 Seems to have superior RFS
D'Angio et al. 1976 (NWTS-1) 1969-1973 Randomized (C) 1. Dactinomycin & Vincristine Inferior RFS
2. Vincristine Not reported

Preceding treatment

Chemotherapy

6-week cycle for 3 cycles, then 3-month cycle for 4 cycles

References

  1. Wolff JA, Newton WA Jr, Krivit W, D'Angio GJ. Single versus multiple dose dactinomycin therapy of Wilms's tumor: a controlled co-operative study conducted by the Children's Cancer Study Group A (formerly Acute Leukemia Co-operative Chemotherapy Group A). N Engl J Med. 1968 Aug 8;279(6):290-4. link to original article PubMed
    1. Update: Wolff JA, D'Angio G, Hartmann J, Krivit W, Newton WA Jr. Long-term evaluation of single versus multiple courses of actinomycin D therapy of Wilms's tumor. N Engl J Med. 1974 Jan 10;290(2):84-6. link to original article contains dosing details in manuscript PubMed
  2. NWTS-1: D'Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, Goodwin W, Leape LL, Sinks LF, Sutow W, Tefft M, Wolff J. The treatment of Wilms' tumor: Results of the national Wilms' tumor study. Cancer. 1976 Aug;38(2):633-46. link to original article PubMed

Dactinomycin & Vincristine

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
D'Angio et al. 1976 (NWTS-1) 1969-1973 Randomized (E-RT-esc) 1. Dactinomycin
2. Vincristine 		Superior RFS
D'Angio et al. 1981 (NWTS-2) 1974-1978 Randomized (E-RT-de-esc) Dactinomycin & Vincristine; longer duration Did not meet primary endpoint of RFS
D'Angio et al. 1989 (NWTS-3) 1979-1985 Randomized (E-RT-de-esc) Dactinomycin & Vincristine; longer duration Did not meet primary endpoint of RFS
Ritchey et al. 2001 (NWTS-4) 1986-1994 Non-randomized (RT)
de Kraker et al. 2004 (SIOP 93-01) 1993-2000 Phase 3 (E-de-esc) Prolonged chemotherapy Equivalent EFS
Pritchard-Jones et al. 2015 (SIOP WT 2001) 2001-2009 Phase 3 (E-de-esc) Dactinomycin, Doxorubicin, Vincristine Non-inferior EFS24 (primary endpoint)

Note: Ritchey et al. 2001 does not appear to be a primary publication of the NWTS-4 results, but no other publications could be found; details including phase of study are unclear.

Preceding treatment

Chemotherapy

  • Dactinomycin (Cosmegen) 45 mcg/kg (maximum dose of 2 mg) IV bolus once on day 8
  • Vincristine (Oncovin) as follows:
    • Cycles 1 & 2: 1.5 mg/m2 (maximum dose of 2 mg) IV bolus once per day on days 1, 8, 15
    • Cycle 3: 1.5 mg/m2 (maximum dose of 2 mg) IV bolus once per day on days 1 & 8
    • Cycles 4 to 9: 1.5 mg/m2 (maximum dose of 2 mg) IV bolus once per day on days 8 & 15

21-day cycle for 9 cycles

References

  1. NWTS-1: D'Angio GJ, Evans AE, Breslow N, Beckwith B, Bishop H, Feigl P, Goodwin W, Leape LL, Sinks LF, Sutow W, Tefft M, Wolff J. The treatment of Wilms' tumor: Results of the national Wilms' tumor study. Cancer. 1976 Aug;38(2):633-46. link to original article PubMed
  2. NWTS-2: D'Angio GJ, Evans A, Breslow N, Beckwith B, Bishop H, Farewell V, Goodwin W, Leape L, Palmer N, Sinks L, Sutow W, Tefft M, Wolff J. The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study. Cancer. 1981 May 1;47(9):2302-11. link to original article PubMed
  3. NWTS-3: D'Angio GJ, Breslow N, Beckwith JB, Evans A, Baum H, deLorimier A, Fernbach D, Hrabovsky E, Jones B, Kelalis P, Othersen B, Tefft M, Thomas PRM. Treatment of Wilms' tumor: results of the Third National Wilms' Tumor Study. Cancer. 1989 Jul 15;64(2):349-60. link to original article PubMed
  4. NWTS-4: Ritchey ML, Shamberger RC, Haase G, Horwitz J, Bergemann T, Breslow NE. Surgical complications after primary nephrectomy for Wilms' tumor: report from the National Wilms' Tumor Study Group. J Am Coll Surg. 2001 Jan;192(1):63-8. link to original article PubMed
  5. SIOP 93-01: de Kraker J, Graf N, van Tinteren H, Pein F, Sandstedt B, Godzinski J, Tournade MF; SIOP. Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial. Lancet. 2004 Oct 2-8;364(9441):1229-35. link to original article PubMed NCT00003804
  6. SIOP WT 2001: Pritchard-Jones K, Bergeron C, de Camargo B, van den Heuvel-Eibrink MM, Acha T, Godzinski J, Oldenburger F, Boccon-Gibod L, Leuschner I, Vujanic G, Sandstedt B, de Kraker J, van Tinteren H, Graf N; SIOP Renal Tumours Study Group. Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial. Lancet. 2015 Sep 19;386(9999):1156-64. Epub 2015 Jul 9. link to original article contains dosing details in manuscript PubMed NCT00047138
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