- Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).
- Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.
- Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.
- Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.
- Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.
OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).
- Stratum I (very low-risk disease): Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.
- Stratum II (standard-risk, stage I or II disease with adverse biological marker): Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV over 15-120 minutes for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.
- Stratum III (standard-risk, stage III disease): Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.
After completion of study treatment, patients are followed periodically for up to 8 years.
- Histologically confirmed Wilms' tumor
- Newly diagnosed stage I-III disease
- Favorable histology
- No moderate- or high-risk Wilms' predisposition syndromes
- Must meet 1 of the following disease stratification categories:
- Very low-risk disease
- Stage I disease
- Age < 2 years
- Tumor weight < 550 g
- Regional lymph nodes histologically negative (must have been sampled)
- No pulmonary metastases on CT scan of chest
- No synchronous bilateral Wilms tumors (Stage V)
- Not predisposed to develop bilateral Wilms tumors, defined as unilateral Wilms tumor and any of the following:
- Beckwith-Wiedemann syndrome
- Isolated hemihypertrophy
- Simpson-Golabi-Behmel syndrome
- Denys-Drash syndrome or other associated genito-urinary anomalies
- Multicentric WT or unilateral WT with contralateral nephrogenic rest(s) in a child < 1 year of age
- Diffuse hyperplastic perilobar nephroblastomatosis
- Also excluded are the following:
- Patients with familial Wilms tumor defined as one of the following:
- Wilms tumor in a patient with a known constitutional familial Wilms tumor gene mutation
- Wilms tumor in a patient who has at least one first-degree or second-degree relative with Wilms tumor (sibling, parent, aunt/uncle, grandparent, cousin)
- Standard-risk disease meeting 1 of the following criteria:
- Disease does not require radiotherapy
- LOH at chromosomes 1p and 16q for stage I or II
- Stage I disease meeting 1 of the following criteria:
- Age ≥ 2 years to age < 30 years
- Tumor weight ≥ 500 g
- Stage II disease
- Age < 30 years
- Any tumor weight
- Disease requires radiotherapy
- No LOH at chromosomes 1p and 16q*
- Stage III disease NOTE: *Patients with combined loss of heterozygosity at chromosomes 1p and 16q will be eligible to transfer to protocol COG-AREN0533
- Must be enrolled on protocol COG-AREN03B2
- Karnofsky performance status (PS) 50-100% for patients > 16 years old
- Lansky PS 50-100% for patients ≤ 16 years old
- Bilirubin (direct) ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram (standard-risk disease)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patient must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior tumor-directed chemotherapy or radiotherapy
- Patients transferring from AREN03B2 with LOH 1p and 16q allowed
Last updated: 11/22/2012