eMedicine Specialties > Pediatrics: General Medicine > Oncology
Clear Cell Sarcoma of the Kidney: Treatment & Medication
Updated: Feb 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The approach for treating clear cell sarcoma of the kidney (CCSK) is different from the approach for Wilms tumor because the overall survival of children with clear cell sarcoma of the kidney remains considerably lower than that of patients with favorable-histology Wilms tumor. In the third National Wilms Tumor Study (NWTS-3), the addition of doxorubicin to the combination of vincristine, dactinomycin, and radiation therapy resulted in an improvement in disease-free survival in patients with clear cell sarcoma of the kidney.8
NWTS-4 showed that patients treated with vincristine, doxorubicin, and dactinomycin for 15 months had an improved relapse-free survival rate compared with patients treated for 6 months (87.5% vs 60.6% at 8 y).6 The overall survival has improved for patients with clear cell sarcoma of the kidney from NWTS-3 to NWTS-4 (83% vs 66.9% at 8 y). The 8-year relapse-free survival rate for localized clear cell sarcoma of the kidney stages I-III is 88%, but late relapses have been known to occur. In the NWTS-5 protocol, patients with all stages of CCSK are treated with the same regimen used in patients who have Wilms tumor with diffuse anaplasia (excluding stage I);8 this treatment consists of a radical nephrectomy followed by radiotherapy and chemotherapy with cyclophosphamide, etoposide, vincristine, and doxorubicin for 24 weeks.
In the NWTSG series that was reviewed by Argani et al, a better prognosis was indicated in the subset of patients with clear cell sarcoma of the kidney that was characterized by stage I tumors in patients aged 2-4 years in whom no tumor necrosis was identified.4
In the current Children's Oncology Group protocol (AREN0321), all patients with clear cell sarcoma of the kidney, except patients with stage IV, continue treatment as in NWTS-5. However, patients with stage I who undergo lymph node sampling do not undergo radiation therapy to the tumor bed. Any patient with stage I who has not undergone lymph node sampling is upstaged to stage II. Patients with stage IV undergo treatment with irinotecan and vincristine in an upfront window approach before treatment with cyclophosphamide, etoposide, vincristine, doxorubicin, and cyclophosphamide.
Surgical Care
At presentation, radical nephrectomy is the initial treatment of choice if the lesion is resectable. If the size or extension of the lesion is in question, a biopsy is performed, and chemotherapy is administered, followed by surgical resection after a response has been obtained.
Consultations
- Radiotherapist: Once the tumor has been resected, the tumor bed and any other sites of disease are irradiated.
- Pediatric oncologist: Primary care physicians should consult with a pediatric oncologist to determine standard and investigational treatment protocols.
Diet
No special diet is required.
Activity
Patients with clear cell sarcoma of the kidney are advised not to participate in contact sports, especially football. Other activity recommendations are made on an individual basis.
Medication
Patients with clear cell sarcoma of the kidney (CCSK) are treated with combination chemotherapy. The addition of doxorubicin to chemotherapeutic regimens has been shown to improve disease-free survival rates. Physicians caring for a patient with clear cell sarcoma of the kidney should consult a pediatric oncologist affiliated with a cancer center that participates in national or international trials to determine the current standard treatment protocol and to determine whether the patient is eligible for an investigational protocol.
Antineoplastic agents
Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (ie, gap 1 [G1]), followed by DNA synthesis (ie, S phase), a premitotic phase (ie, gap 2 [G2]), and, finally, mitotic cell division (ie, M phase).
The rate of cell division varies among tumors. Most lesions of common cancers increase very slowly in size compared to normal tissues, and the rate of growth may even be slower in large tumors. This difference allows normal cells to recover more quickly from chemotherapy than malignant cells, and provides the rationale behind current cyclic dosage schedules.
Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, while others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism in many antineoplastic agents.
Refer to the specific protocols for duration of therapy with each drug and timing of administration within each treatment cycle.
Vincristine (Oncovin)
A vinca alkaloid that inhibits cellular mitosis by inhibiting intracellular tubulin function, binding to microtubules, and inhibiting the synthesis of spindle proteins.
Adult
Pediatric
Weeks 1, 2, 4-8, 10, and 11:
<30 kg: 0.05 mg/kg IV push
>30 kg: 1.5 mg/m2; not to exceed 2 mg/dose
Weeks 13, 18, and 24:
<30 kg: 0.067 mg/kg IV push
>30 kg: 2 mg/m2; not to exceed 2 mg/dose
Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; asparaginase, CYP450 3A4 inhibitors (eg, itraconazole, quinupristin/dalfopristin, sertraline, ritonavir), CSF (eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP450 3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects
Documented hypersensitivity; IT administration may cause death
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in severe cardiopulmonary disease, hepatic impairment (adjust dose), or preexisting neuromuscular dysfunction; may increase conjugated bilirubin
Doxorubicin (Adriamycin, Rubex)
Inhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. The combination of these 2 events can, in turn, inhibit the growth of neoplastic cells.
Adult
Pediatric
Day 0, weeks 6, 12, 18, and 24:
<30 kg: 1.5 mg/kg IV
>30 kg: 45 mg/m2
Note: Dose at week 6 should be decreased by 50% if whole lung or whole abdomen radiotherapy is administered
May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin
Documented hypersensitivity; severe heart failure, cardiomyopathy, and impaired cardiac function; preexisting myelosuppression
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 patients with impaired hepatic function
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
Pediatric
Weeks 3, 9, 15, and 21:
<30 kg: 14.7 mg/kg/d IV for 5 d
>30 kg: 440 mg/m2/d IV for 5 d
Weeks 6, 12, 18, and 24: Administer according to weight as above for 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
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profiles (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Etoposide (Toposar, VePesid, VP-16)
Inhibits topoisomerase II and causes DNA strand breakage causing cell proliferation to arrest in late S or early G2 portion of the cell cycle.
Adult
Pediatric
Weeks 3, 9, 15, and 21:
<30 kg: 3.3 mg/kg/d IV for 5 d
>30 kg: 100 mg/m2/d IV for 5 d
May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Bleeding and severe myelosuppression may occur
Uroprotective antidote
Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide.
In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide or cyclophosphamide metabolite considered responsible for urotoxicity.
Mesna (Mesnex)
Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. Dose is dependent on dose of ifosfamide or cyclophosphamide, typically 60-100% of the antineoplastic agent used. May be administered as an initial bolus followed by IV continuous infusion or as intermittent IV infusions before and following chemotherapy regimen.
Adult
Pediatric
Begin administration following cyclophosphamide
Weeks 3, 9, 15, and 21:
<30 kg: 3 mg/kg/dose IV over 15 min q3h for 4 doses/d for 5 d
>30 kg: 90 mg/m2/dose IV over 15 min q3h for 4 doses/d for 5 d
Weeks 6, 12, 18, and 24: Administer according to weight as above for 3 d
May increase warfarin effects, adjust dose according to INR target
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor morning urine for hematuria before ifosfamide or cyclophosphamide dose; common adverse effects include hypotension, headache, GI tract toxicity, and limb pain
Colony-stimulating growth factors
These act as a hematopoietic growth factor that stimulates the development of granulocytes. They are used to treat or prevent neutropenia in patients receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. They are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and to manage chronic neutropenia.
Filgrastim (Neupogen, G-CSF)
Granulocyte colony-stimulating factor that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.
Adult
Pediatric
5 mcg/kg/d SC beginning 24 h after the last dose of chemotherapy, administered until ANC >10,000/mcL and beyond nadir for myelosuppression or minimum of 1 wk
Do not use 12-24 h before or 24 h after administering cytotoxic chemotherapy because increases sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Risk of developing myelodysplastic syndrome or acute myeloid leukemia in certain patients; leukocytosis; possible tumor growth
More on Clear Cell Sarcoma of the Kidney |
| Overview: Clear Cell Sarcoma of the Kidney |
| Differential Diagnoses & Workup: Clear Cell Sarcoma of the Kidney |
 Treatment & Medication: Clear Cell Sarcoma of the Kidney |
| Follow-up: Clear Cell Sarcoma of the Kidney |
| Multimedia: Clear Cell Sarcoma of the Kidney |
| References |
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References
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Further Reading
Keywords
clear cell sarcoma of the kidney, CCSK, bone-metastasizing renal tumor, renal sarcoma, clear cell cancer, kidney cancer, kidney sarcoma, renal cancer, renal dysplasia, hypertension, hematuria
