eMedicine Specialties > Pediatrics: General Medicine > Oncology
Wilms Tumor: Treatment & Medication
Updated: Mar 3, 2009
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Treatment
Medical Care
The usual approach in most patients is nephrectomy followed by chemotherapy with or without postoperative radiotherapy. Table 1 summarizes the current approach to patients with favorable histology Wilms tumor according to the current COG studies. Children found to have loss of heterozygosity (LOH) at 1p and 16q receive more aggressive chemotherapy as they have a worse prognosis compared with children without LOH at 1p and 16q.5
Table 1. Current Approach to Favorable Histology Wilms Tumor by Stage
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Table
| Stage and Histology | Surgery | Chemotherapy | Radiation Therapy* |
|---|---|---|---|
Stage I or II favorable histology without LOH 1p and 16q † | Nephrectomy | Vincristine, dactinomycin | No |
Stage I or II favorable histology with LOH 1p and 16q | Nephrectomy | Vincristine, dactinomycin, doxorubicin | No |
Stage III and IV favorable histology without LOH 1p and 16q | Nephrectomy | Vincristine, dactinomycin, doxorubicin | Yes |
Stage III and IV favorable histology with LOH 1p and 16q | Nephrectomy | Vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide | Yes |
| Stage and Histology | Surgery | Chemotherapy | Radiation Therapy* |
|---|---|---|---|
Stage I or II favorable histology without LOH 1p and 16q † | Nephrectomy | Vincristine, dactinomycin | No |
Stage I or II favorable histology with LOH 1p and 16q | Nephrectomy | Vincristine, dactinomycin, doxorubicin | No |
Stage III and IV favorable histology without LOH 1p and 16q | Nephrectomy | Vincristine, dactinomycin, doxorubicin | Yes |
Stage III and IV favorable histology with LOH 1p and 16q | Nephrectomy | Vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide | Yes |
* The current dose for radiation therapy for favorable histology Wilms tumor is approximately 1080 cGy for the abdomen and 1200 cGy for the lung.13 Postoperative radiotherapy is started within 14 days of nephrectomy.14 Patients with stage IV favorable histology Wilms tumor and lung metastases whose pulmonary lesions do not disappear after 6 weeks of chemotherapy receive whole-lung radiation therapy.
† Some evidence suggests that certain children with stage I disease and favorable histology do well with nephrectomy alone.15 Children younger than 24 months with small (<550 g) Wilms tumors with favorable histology are noted in the current COG protocol.
Currently, patients enrolled on COG AREN0321 protocol for high risk Wilms tumor are treated as follows:
- Patients with focal anaplastic stage I-III Wilms tumors and diffuse anaplastic stage I Wilms tumors undergo nephrectomy followed by vincristine, actinomycin-D, and doxorubicin in addition to local radiotherapy.
- Patients with focal anaplastic stage IV Wilms tumors and diffuse anaplastic stage II-III tumors undergo the same treatment, with the addition of cyclophosphamide, etoposide, and carboplatin.
- More aggressive treatment is delivered for stage IV diffuse anaplastic Wilms tumors; nephrectomy is followed by initial irinotecan and vincristine administration, followed by actinomycin-D, doxorubicin, cyclophosphamide, carboplatin, etoposide, and radiotherapy.
Consultations
The patient should be referred to a pediatric surgeon, a pediatric oncologist, and, in some cases, a radiation oncologist.
Diet
No special diet is recommended.
Activity
No precautions regarding activity are advised, although the patient and his or her parents should be aware that the patient has only one kidney after therapy. Activities that carry an inherent risk of kidney injury, such as boxing and hockey, should be avoided.
Medication
Antineoplastic agents
Chemotherapy agents used to treat patients with Wilms tumor depend on the stage and histology of disease. Commonly used agents include dactinomycin, vincristine, doxorubicin, cyclophosphamide, etoposide, and carboplatin. The dosage depends on the particular stage of disease and on the child.
Dactinomycin (Cosmegen, actinomycin D)
Antibiotic derived from Streptomyces bacterium. Binds to guanine portion of DNA and causes topoisomerase-mediated breaks in DNA strands.
Adult
0.5 mg IV injection qd for 5 d
Pediatric
0.015 mg/kg IV injection qd for 5 d, or 1.5 mg IV push q3wk
May decrease immune response to live-virus vaccines; increased hepatotoxicity with enflurane or halothane
Documented hypersensitivity; chicken pox; herpes zoster; concomitant radiation
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Vesicant, use extravasation precautions; may cause nausea, vomiting, diarrhea, stomatitis, myelosuppression, hepatotoxicity, dermatitis, or hyperpigmentation (especially if patient received radiation)
Vincristine (Oncovin)
Inhibits tubulin polymerization; therefore, targets dividing cells.
Adult
2 mg IV; slowly inject into central venous catheter or fresh IV line (vesicant)
Pediatric
1.5 mg/m2 IV q1-3wk; not to exceed 2 mg/dose
Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; asparaginase, cytochrome P450 (CYP) 3A4 inhibitors (eg, itraconazole, quinupristin-dalfopristin, sertraline, ritonavir), GM-CSF (eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects; may decrease immune response to live-virus vaccines
Hypersensitivity; intrathecal use (universally fatal); severe neurotoxicity from previous dose; Charcot-Marie-Tooth syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause nausea, vomiting, diplopia, neuromyopathy, myelosuppression, alopecia, or constipation; caution in severe cardiopulmonary disease, hepatic impairment (adjust dosage), or preexisting neuromuscular dysfunction
Cyclophosphamide (Cytoxan)
Alkylating agent, believed to be cytotoxic to dividing cells by cross-linking cellular DNA. Processed in liver to active metabolites; byproducts (eg, acrolein) accumulate in bladder and cause cystitis.
Adult
400 mg/m2 PO qd for 5 d
1-1.5 g/m2 IV q3-4wk
Pediatric
1.2-2.2 g/m2 IV qd for 1-3 d
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity; may decrease immune response to live-virus vaccines
Documented hypersensitivity; severely depressed bone marrow function; severe hemorrhagic cystitis
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause nausea, vomiting, alopecia, cardiomyopathies, or hemorrhagic cystitis (administer with mesna); regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Etoposide (Toposar, VP16)
Inhibits topoisomerase II; therefore, toxic to cells undergoing DNA replication.
Adult
50-100 mg/m2/d IV qd for 5 d; PO dose is 2 times IV dose rounded to nearest 50 mg
Pediatric
100 mg/m2 IV qd for 5 d
May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells; may decrease immune response to live-virus vaccines
Documented hypersensitivity to podophyllum
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause nausea, vomiting, myelosuppression, or alopecia; adjust dosage for renal or liver impairment, low serum albumin level, or bone marrow suppression; monitor for hypotension during infusion
Carboplatin (Paraplatin)
Analog of cisplatin. Used in treatment regimens for relapse.
Dose based on the following equation: Total dose (in milligrams) = (target AUC) X (GFR + 25) or (target AUC) X [GFR + (0.36 X body weight in kilograms)], where AUC is the area under plasma concentration-time curve expressed in milligrams per milliliter per minute, and GFR is the glomerular filtration rate expressed in milliliters per minute.
Adult
Pediatric
500 mg/m2 IV for 2 d each cycle
Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs; may decrease immune response to live-virus vaccines
Documented hypersensitivity; severe myelosuppression; clinically significant bleeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause myelosuppression, peripheral neuropathy, or electrolyte disturbance
Doxorubicin (Adriamycin)
Cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius (var caesius). Binds to nucleic acids presumably by specific intercalation of anthracycline nucleus with DNA double helix
Adult
Pediatric
45 mg/m2 IV; reduce to 22.5 mg/m2 when (only when) whole-lung or whole-abdomen radiation therapy is being administered
May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity
Documented hypersensitivity; previous treatment with complete cumulative doses of doxorubicin, daunorubicin, idarubicin, and/or anthracyclines and anthracenes
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in impaired hepatic function
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| Follow-up: Wilms Tumor |
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References
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Further Reading
Keywords
Wilms tumor, Wilms' tumor, nephroblastoma, synchronous bilateral Wilms tumor, metachronous bilateral Wilms tumor, National Wilms Tumor Study, NWTS, National Wilms Tumor Study Group, NWTSG, International Society of Pediatric Oncology, SIOP, WAGR syndrome, Beckwith-Wiedemann syndrome, BWS, Denys-Drash syndrome, Denys-Drash syndrome, visceromegaly, macroglossia, hyperinsulinemic hypoglycemia, urinary tract infection, varicocele, hypertension, hypotension, cryptorchidism, horseshoe kidney, hypospadias
