All patients with Stage I PFH hepatoblastoma will be classified as very low-risk (stratum 1) and will be treated with surgery only. Patients with Stage I non-PFH, non-SCU hepatoblastoma or with Stage II non-SCU hepatoblastoma will be classified as low-risk (stratum 2)and will be treated on Regimen T with 2 adjuvant cycles of cisplatin, 5-flouorouracil, and vincristine (C5V), a reduction from the standard 4 cycles of chemotherapy given on previous COG trials. Patients with Stage I SCU, Stage II SCU, or any Stage III hepatoblastoma will be classified as intermediate-risk (stratum 3) and will be treated with Regimen F. This treatment regimen is based on previous COG trials that administered 6 cycles of C5V therapy plus surgical resection of the tumor. However, to improve resection and survival rates, doxorubicin, an agent with proven efficacy will be added to the C5V therapy (C5VD). All patients with any Stage IV hepatoblastoma as well as patients with any stage of hepatoblastoma and initial AFP and amp;lt; 100 ng/mL will be classified as high-risk (stratum 4) and will be treated with a novel agent (irinotecan) in Regimen W in order to improve survival. This regimen includes 2 cycles of [Double Quote]up-front[Double Quote] irinotecan window therapy combined with vincristine therapy. Patients who respond to vincristine/irinotecan will be considered responders. Responder patients will then receive a total of 6 cycles of C5VD therapy with 1 cycle of VI in between each 2-cycle block of C5VD. Non-responder patients will only receive the 6 cycles of C5VD following the [Double Quote]up-front[Double Quote] window therapy.
* Patients must be <= 21 years of age at the time of diagnosis.
* Patients must be newly diagnosed with histologically-proven hepatoblastoma. In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations as outlined in the protocol, but is too ill to undergo a biopsy safely, the patient may be enrolled on AHEP0731 without a biopsy. For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur: The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha-fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment. Patient must be enrolled on AHEP0731 prior to initiating protocol therapy. Per protocol, a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment. If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims. Patients will be staged for Risk Classification and Treatment at diagnosis using COG Staging Guidelines, as listed in the protocol. At the time of study enrollment, the patient[Single Quote]s treatment regimen must be identified. If the patient[Single Quote]s primary tumor was resected prior to the day of enrollment and a blood specimen for the determination of serum alpha-fetoprotein was not obtained prior to that surgery, the patient will be considered to have alpha-fetoprotein of greater than 100 ng/mL for the purpose of treatment assignment. If tumor samples obtained prior to the date of enrollment were not sufficient to determine whether small cell undifferentiated (SCU) histology was present, treatment assignment will be made assuming SCU is not present in the tumor. For patients with Stage I or II disease, specimens for rapid central review have been submitted and the rapid central review diagnosis and staging must be available to be provided on the AHEP0731 Eligibility CRF.
* Patients must have a performance status corresponding to ECOG scores of 0, 1, or 2 (Karnofsky for patients > 16 years of age and Lansky for patients <= 16 years of age).
* Patients may have had surgical resection of some or all sites of hepatoblastoma prior to enrollment.
* Organ function requirements are not required for enrolled patients who are Stage I, PFH and will not be receiving chemotherapy.
* Adequate renal function defined as: Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2 OR a serum creatinine based on age/gender as listed in the protocol.
* For patients who will be assigned to protocol chemotherapy, adequate liver function defined as: Total bilirubin < 1.5 x upper limit of normal (ULN) for age, and SGOT (AST) or SGPT (ALT) < 10 x ULN for age.
* For patients who will be assigned to protocol chemotherapy, adequate bone marrow function defined as: Absolute neutrophil count (ANC) > 750/[MICRO-SYMBOL]L, Platelet count > 75,000/[MICRO-SYMBOL]L
* For intermediate- and high-risk patients who will be assigned to protocol chemotherapy, adequate cardiac function defined as: Shortening fraction >= 27% by echocardiogram, or Ejection fraction >= 47% by radionuclide angiogram (MUGA). Note: the echocardiogram (or MUGA) may be done within 28 days prior to enrollment.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, FDA, and NCI requirements for human studies must be met.