eMedicine Specialties > Pediatrics: General Medicine > Oncology
Neuroblastoma: Treatment & Medication
Updated: Jul 31, 2009
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Treatment
Medical Care
Care of children with neuroblastoma is provided by a multidisciplinary team involving pediatric oncology, radiation oncologists, surgeons, and anesthesiologists, as well as nurse practitioners, nurses, pharmacists, psychologists, and physical and occupational therapists dedicated to the special needs of these children.
The table below outlines criteria for risk assignment based on the International Neuroblastoma Staging System (INSS), age, and biologic risk factors. This, in turn, determines the intensity of the therapy. These treatment strategies have been developed from more than 2 decades of experience with clinical trials in Children's Cancer Group (CCG) and Pediatric Oncology Group (POG), now known as the Children's Oncology Group (COG). Correlative biologic studies were pivotal in identifying biologic risk factors important for outcome. Currently, efforts are ongoing to develop an International Neuroblastoma Risk Group (INRG).
In addition, recently published results on correlative biologic studies and clinical outcome have lead to changes in an age cut-off of more than 365 days (365-547 d) for some patients with tumors in stages 3 and 4.9,10 These criteria are based on the analysis of several thousands of patients treated in cooperative group protocols in Australia, Canada, Europe, Japan, and the United States.11
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Table
| Risk Group | Stage | Age | MYCN Amplification Status | Ploidy | Shimada |
| Low | 1 | Any | Any | Any | Any |
| Low | 2a/2b | Any | Non-amp | Any | Any |
| High | 2a/2b | Any | Amp | Any | Any |
| Intermediate | 3 | <547d | Non-amp | Any | Any |
| Intermediate | 3 | ³ 547d | Non-amp | Any | Favorable |
| High | 3 | Any | Amp | Any | Any |
| High | 3 | ³ 547d | Non-amp | Any | Unfavorable |
| High | 4 | <365d | Amp | Any | Any |
| Intermediate | 4 | <365d | Non-amp | Any | Any |
| High | 4 | 365-547d | Amp | Any | Any |
| High | 4 | 365-547d | Any | Diploid | Any |
| High | 4 | 365-547 | Any | Any | Unfavorable |
| Intermediate | 4 | 365-547d | Non-amp | Hyper | Favorable |
| High | 4 | ³ 547d | Any | Any | Any |
| Low | 4s | <365d | Non-amp | Hyper | Favorable |
| Intermediate | 4s | <365d | Non-amp | Diploid | Any |
| Intermediate | 4s | <365d | Non-amp | Any | Unfavorable |
| High | 4s | <365d | Amp | Any | Any |
| Risk Group | Stage | Age | MYCN Amplification Status | Ploidy | Shimada |
| Low | 1 | Any | Any | Any | Any |
| Low | 2a/2b | Any | Non-amp | Any | Any |
| High | 2a/2b | Any | Amp | Any | Any |
| Intermediate | 3 | <547d | Non-amp | Any | Any |
| Intermediate | 3 | ³ 547d | Non-amp | Any | Favorable |
| High | 3 | Any | Amp | Any | Any |
| High | 3 | ³ 547d | Non-amp | Any | Unfavorable |
| High | 4 | <365d | Amp | Any | Any |
| Intermediate | 4 | <365d | Non-amp | Any | Any |
| High | 4 | 365-547d | Amp | Any | Any |
| High | 4 | 365-547d | Any | Diploid | Any |
| High | 4 | 365-547 | Any | Any | Unfavorable |
| Intermediate | 4 | 365-547d | Non-amp | Hyper | Favorable |
| High | 4 | ³ 547d | Any | Any | Any |
| Low | 4s | <365d | Non-amp | Hyper | Favorable |
| Intermediate | 4s | <365d | Non-amp | Diploid | Any |
| Intermediate | 4s | <365d | Non-amp | Any | Unfavorable |
| High | 4s | <365d | Amp | Any | Any |
Cooperative Group Treatment Strategies
Low-risk group treatment strategy
Patients with localized respectable neuroblastoma (stage 1) have excellent event-free survival (EFS) rates with surgical excision of tumor only. Adjuvant chemotherapy is generally not needed for this group of patients. Even the presence of residual microscopic disease does not significantly affect the EFS. If patients develop recurrent disease, chemotherapy can be used, and the overall survival rate remains higher than 95%.
Similar therapy is offered to patients with stage 2A/2B disease who are presently assigned to a low-risk category if they have MYCN -non amplified tumors, regardless of age histology or ploidy. Patients with stage 2A/2B disease with amplified MYCN are considered high risk regardless of age and histology.
Most patients with 4S disease (ie, non-MYCN –amplified tumors, favorable histology, hyperdiploid tumors in infants younger than 1 y) are also considered to be in the low-risk group and most experience spontaneous regression. Thus, observation or surgery alone is often all that is needed to manage these tumors. Chemotherapy may be used to control life-threatening situations such as respiratory distress or mechanical obstruction.
Intermediate-risk group treatment strategy
Surgery and multiagent chemotherapy comprise the backbone of therapy for intermediate risk group patients. Current efforts are ongoing to help understand which of this diverse group of patients can have therapy reduced without threatening the excellent EFS for these patients.
Intermediate-risk patients include children younger than 18 months with stage 3 and 4 disease and favorable biology (non-MYCN –amplified tumors, regardless of histology and DNA index). These patients are offered therapy with 4 of the most active drugs against neuroblastoma (ie, cyclophosphamide, doxorubicin, carboplatin, etoposide) for either 4 cycles, 6 cycles, or 8 cycles, depending on histology and DNA index and response to treatment. In these patients, surgery can be performed either at time of diagnosis or following multiagent chemotherapy. If residual disease is present after chemotherapy and surgery, radiation therapy could be considered. However, the use of radiation is controversial, although a POG study suggested that it improves outcome when administered to areas of residual disease postchemotherapy.
High-risk group treatment strategy
This group of patients seem to require treatment with multiagent chemotherapy, surgery, and radiotherapy, followed by consolidation with high-dose chemotherapy and peripheral blood stem cell rescue.
Current therapeutic protocols involve 4 phases of therapy, including induction, local control, consolidation and treatment of minimal residual disease. The 3-year EFS for patients in the high-risk group who are treated without such high-intensity therapy is less than 20%, compared with an EFS of 38% in patients treated with a single bone marrow transplant and cis-retinoic acid after transplant.
Induction therapy currently involves multiagent chemotherapy with non–cross-resistant profiles, including alkylating agents, platinum, and anthracyclines and topoisomerase II inhibitors. Current studies are ongoing to look at addition of topoisomerase I inhibitors as part of an upfront therapy during induction. Topotecan does display activity against relapsed neuroblastoma.
Local control involves surgical resection of primary tumor site as well as radiation to primary tumor site. Primary tumors are often more amenable to surgical resection after receiving upfront induction chemotherapy. Neuroblastoma is a very radiosensitive tumor, and chemotherapy plays an important role in control of disease in the high-risk setting.
Myeloablative consolidation therapy has shown to improve EFS for patients with high-risk neuroblastoma. Current data from trials in the United States and Europe support improved outcomes for patients receiving myeloablative consolidation therapy with etoposide, carboplatin, and melphalan. Recently, a single-arm study of tandem stem cell transplantation reported an EFS of 58%. A randomized study of tandem stem cell transplant against a single transplant is currently ongoing in the Children's Oncology Group.6 Because of significant improvements in time to recovery and a lower risk of tumor cell contamination, most centers now recommend the use of peripheral blood stem cell support over bone marrow for consolidation therapy.
Control of minimal residual disease with biologic agents has also been shown to improve survival. The most experience is with 13-cis -retinoic acid in a maintenance phase of therapy. This agent has been shown to cause differentiation in neuroblastoma cell lines. CCG-3891 showed a significant survival advantage with 3-year EFS of 38% for those patients receiving maintenance therapy with 13-cis -RA compared with 18% for those who did not receive this therapy. Recent data have showed improved survival in patients receiving 13-cis -RA in combination with immunomodulatory therapy with interleukin (IL)-2, granulocyte macrophage colony-stimulating factor (GM-CSF), and the chimeric anti-GD2 (gangliosidase) antibody when compared with 13-cis -RA alone.
Future directions and experimental therapies
Other experimental therapies are currently under investigation for recurrent high-risk neuroblastoma, including aurora kinase inhibitors, antiangiogenic agents, histone deacetylase inhibitors, and therapeutic metaiodobenzylguanidine (MIBG).
Surgical Care
Surgical resection plays an important role in the treatment of patients with neuroblastoma. For patients with localized disease, surgical resection is curative. For patients with regional or metastatic disease, surgery to establish a diagnosis and obtain adequate samples for biologic studies is essential. Typically, second-look surgery postchemotherapy is used to attempt a complete resection. The emphasis in the second-look procedure is as complete a debulking as possible without sacrificing major organ function. Patients with residual disease postchemotherapy and surgery may benefit from the use of radiotherapy.
Consultations
Neuroblastoma can be confused with other neoplastic or nonneoplastic diseases of childhood. The diagnosis can be challenging in the 10% of patients who present with normal urinary catecholamines.
Radiation oncologists may participate in the care of patients with neuroblastoma. Typically, they are consulted to evaluate patients whenever radiation therapy is a consideration. Usually, radiotherapy is localized to areas of residual microscopic disease, persistent disease, or both after chemotherapy and surgery.
In high-risk patients, the need for stem cell harvest and transplantation should be anticipated. These services should be included early in the planning phase of treatment.
Diet
Nutrition plays an important role in therapy. Children need adequate caloric intake to attain normal growth and development, and to recover from the adverse effects of therapy. Nutritionists typically help to provide adequate supportive care during therapy. Supplemental nutrition is often required during therapy. This should occur via the enteral route (nasogastric or gastric tube). The parenteral route should be used only after failure to supplement adequately using enteral feedings.
Activity
No specific restrictions are placed on activity. Patients who are thrombocytopenic should avoid strenuous activity and contact sports. Patients should avoid ill contacts, especially if neutropenic.
Medication
All chemotherapy orders are written by pediatric oncologists and countersigned, usually by another physician. With recurrent disease, various salvage protocols may be used; with refractory disease, a limited number of phase I/II studies are available through the Children's Oncology Group (COG) and New Approaches to Neuroblastoma Therapy (NANT) consortia.
Resources presented in this section should serve as a guide to indication, usual dosages, and adverse effects of specific agents. Antineoplastic drugs have a narrow therapeutic index and effective doses usually cause severe toxicities, some of which can be life threatening.
Individual chemotherapy drugs are discussed below. These agents are almost invariably given in combination. Commonly used combinations include the following:
- Vincristine, cyclophosphamide, and doxorubicin
- Carboplatin and etoposide
- Cisplatin and etoposide
- Ifosfamide and etoposide
- Cyclophosphamide and topotecan
Consolidation regimens used in neuroblastoma include the following:
- Carboplatin and etoposide with melphalan or cyclophosphamide
- Thiotepa and cyclophosphamide
- Melphalan and total body irradiation
In Europe, several studies have used busulfan with melphalan or cyclophosphamide. One commonly used salvage or relapse therapy regimen is the combination of topotecan and cyclophosphamide. The use or retinoids have been incorporated in maintenance regimens in the posttransplant setting. Irinotecan is also under investigation.
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, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2), which is followed by a mitotic cell division (ie, phase M).
Cell division rate varies for different tumors. Most common cancers increase very slowly in size compared with normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly from chemotherapy than malignant cells; it is the rationale behind current cyclic dosage schedules.
Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.
Carboplatin (Paraplatin)
Alkylating agent. Interferes with metabolism of DNA by covalent binding.
Adult
Pediatric
500 mg/m2 IV qd for 2 d; usually administered with etoposide, alternating with other drug combinations q3-4wk
For marrow ablation: 667-1000 mg/m2 IV qd for 3 d in combination with etoposide and cyclophosphamide or with etoposide and melphalan
Incidence of neurotoxicity and nephrotoxicity is higher in patients who previously have been treated with cisplatin; however, the incidence of both these complications is lower with carboplatin than cisplatin
Documented hypersensitivity; use in the setting of existing hearing loss should be considered carefully
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC count closely, avoid infectious contacts, and seek care for fever and bleeding; common adverse effects include nausea, vomiting, and myelosuppression; occasional adverse effects include electrolyte disturbances; rare adverse effects include metallic taste, peripheral neuropathy, hepatotoxicity, renal toxicity, ototoxicity, and secondary leukemia
Cisplatin (Platinol)
Mechanism of action is similar to other alkylating agents. Binds and cross-links DNA strands.
Adult
Pediatric
20-40 mg/m2 IV qd for 5 d or a single dose of 90-100 mg/m2, usually combined with etoposide or doxorubicin; requires prehydration; administer with 0.45% NaCl, potassium chloride, and mannitol
Increased risk of ototoxicity with aminoglycosides; interacts with probenecid and sulfinpyrazone and causes increased risk of uric acid nephropathy
Documented hypersensitivity, preexisting renal insufficiency, myelosuppression, and hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC count closely, avoid infectious contacts, and seek care for fever and bleeding; common adverse effects include nausea, vomiting (highly emetogenic), myelosuppression, ototoxicity; occasional adverse effects include electrolyte disturbances renal toxicity; rare adverse effects include metallic taste, peripheral neuropathy, hepatotoxicity, and secondary leukemia
Cyclophosphamide (Cytoxan)
Immunosuppressant antineoplastic agent. Metabolism of cyclophosphamide by hepatic microsomal enzymes produces active alkylating metabolites, which probably damage DNA.
Adult
Pediatric
1000-2000 mg/m2 IV qd for 2 d; usually with doxorubicin and vincristine; requires hydration before and during infusion; mesna used to prevent urotoxicity
For marrow ablation: 50-100 mg/kg (ideal body weight); bone marrow transplant preparative regimens usually combine etoposide and/or carboplatin; can also be used with thiotepa
Interacts with probenecid and sulfinpyrazone; causes increased risk of uric acid nephropathy; increases anticoagulant activity; at higher doses and with radiotherapy, can increase incidence of cardiomyopathy
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC count closely, avoid infectious contacts, and seek care for fever and bleeding; monitor for hematuria (use with mesna to prevent hemorrhagic cystitis); common adverse effects include anorexia, nausea, vomiting, myelosuppression, alopecia, immunosuppression, and gonadal dysfunction/sterility; occasional adverse effects include metallic taste, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and hemorrhagic cystitis; rare adverse effects include transient blurred vision, arrhythmias and myocardial necrosis (high dose), pulmonary fibrosis, secondary malignancy, and bladder fibrosis
Doxorubicin (Adriamycin)
Causes DNA strand breakage mediated by effects on topoisomerase II. Intercalates into DNA and inhibits DNA polymerase.
Adult
Pediatric
30-75 mg/m2 slow IV push or as continuous IV infusion once during the cycle; usually combined with vincristine and cyclophosphamide or with cisplatin
Probenecid; sulfinpyrazone; may enhance cardiotoxicity with cyclophosphamide, dactinomycin, mitomycin, or radiation
Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC count closely, avoid infectious contacts, and seek care for fever and bleeding; modify doses if total bilirubin is >1.2 mg/dL; common adverse effects include cardiac arrhythmias (rarely clinically significant), nausea, vomiting, worsening of adverse effects caused by radiation, local ulceration if extravasated, pink or red color to urine, myelosuppression, and alopecia, immunosuppression; occasional adverse effects include stomatitis, hepatotoxicity, mucositis, and cardiomyopathy (cumulative, dose-dependent); rare adverse effects include palmar-plantar erythrodysesthesia, anaphylaxis, allergic reactions, rash, and secondary malignancy
Etoposide (VP-16, VePesid)
Interacts with topoisomerase II and produces single strand breaks in DNA. Arrests cells in late S or G2 phase.
Adult
Pediatric
100-200 mg/m2 IV qd for 3 d; alternatively 75-150 mg/m2 IV qd for 5 d; typically combined with ifosfamide, cisplatin, or carboplatin
For marrow ablation: 40-60 mg/kg (ideal body weight); generally combined with carboplatin and cyclophosphamide or melphalan
Additive bone marrow suppression occurs with other chemotherapy or radiation
Life-threatening hypersensitivity; reactions nonresponsive to premedication; many patients with reactions to etoposide can be successfully treated with etoposide phosphate (Etopophos); IT administration may cause death
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
If patient is sensitive to etoposide, use prophylaxis to avoid allergic reactions or consider Etopophos; monitor CBC count closely, avoid infectious contacts, and seek care for fever and bleeding; common adverse effects include nausea and myelosuppression; occasional adverse effects include alopecia, enhanced damage from radiation, and diarrhea; rare adverse effects include hypotension, anaphylaxis, rash, peripheral neuropathy, stomatitis, and secondary malignancy
Ifosfamide (Ifex)
Alkylating agent. Metabolic activation by microsomal liver enzymes produces biologically active intermediates that attack nucleophilic sites, particularly on DNA.
Adult
Pediatric
1.2-2 g/m2 IV qd for 3-5 d with mesna; usually combined with etoposide, vincristine, or doxorubicin; requires concurrent hydration with administration
May have increased nephrotoxicity with other nephrotoxic drugs (eg, cisplatin, carboplatin)
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC count and platelets closely; avoid ill contacts; seek care for fever and bleeding; monitor for hematuria (use with mesna to prevent hemorrhagic cystitis); common adverse effects include nausea, vomiting, anorexia, myelosuppression, and alopecia; occasional adverse effects include somnolence, confusion, weakness, seizure, SIADH, hemorrhagic cystitis, cardiac toxicities with arrhythmias, myocardial necrosis, and Fanconi renal syndrome; rare adverse effects include encephalopathy, peripheral neuropathy, acute renal failure, pulmonary fibrosis, secondary malignancy, and bladder fibrosis
Melphalan (Alkeran)
Inhibits mitosis by cross-linking DNA strands.
Adult
Pediatric
Before bone marrow transplant (ie, administer on pretransplant days -7, -6, -5)
<12 kg: 2 mg/kg/d IV infusion over 24 h for 3 d
>12 kg: 60 mg/m2/d IV infusion over 24 h for 3 d (ie, cumulative dose is 180 mg/m2 over 3 d)
Concurrent administration with cyclosporine increases nephrotoxicity; cimetidine and H2 antagonists increase gastric pH, decreasing effects of melphalan
Documented hypersensitivity; severe bone marrow depression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Amenorrhea may occur; caution in previously diagnosed myelosuppression
Isotretinoin (13-cis-retinoic acid, Accutane)
Vitamin A derivative. Interacts with retinoic acid responsive elements on DNA, which results in gene activation and differentiation of target cells.
Adult
Pediatric
160 mg/m2/d PO divided bid alternating 2 wk on and 2 wk off per mo for 6 mo (alternating dose avoids tachyphylaxis)
Reduce dose if liver enzymes >5 times normal; reduce dose with pancytopenia, musculoskeletal cramps, dry skin, or neurologic symptoms
Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; isotretinoin may reduce plasma levels of carbamazepine
Documented hypersensitivity; pregnancy, infections, headache, vertigo, hypercalcemia, elevated liver enzymes
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Common adverse effects include dry skin, dry mucosa, and cheilitis; occasional adverse effects include nausea, vomiting, rash, conjunctivitis, musculoskeletal pains, fatigue, headache, serum elevations (eg, triglycerides, cholesterol, transaminases), hypercalcemia, urethritis, and dysuria; rare adverse effects include changes in skin pigmentation, nonspecific GI complaints, dizziness, pseudotumor cerebri, anemia, leukopenia, retinoic acid syndrome with hyperleukocytosis, respiratory distress, fever, hypotension, pulmonary infiltrates, and skeletal hyperostosis
Thiotepa (Thioplex)
Ethyleneimine derivative alkylating agent. Action involves transfer of the alkyl group to amino, carboxyl, hydroxyl, imidazole, phosphate, and sulfhydryl groups within the cell, altering structure and function of DNA, RNA, and proteins.
Adult
Before bone marrow transplant (ie, administer on pretransplant days -7, -6, -5):
300 mg/m2 IV qd for 3 d in combination with cyclophosphamide for marrow ablation
Pediatric
Documented hypersensitivity to thiotepa or other phenothiazines; severe hepatic or cardiac disease
CNS depressants, anticholinergics, or antihypertensive agents may increase toxic effects
Documented hypersensitivity; pregnancy, infections, headache, vertigo, hypercalcemia, elevated liver enzymes
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Avoid large dressings or cremes applied to skin during thiotepa administration to limit skin toxicity; monitor CBC count closely, avoid infectious contacts, and seek care for fever and bleeding; common adverse effects include nausea, vomiting, myelosuppression, mucositis and esophagitis (high doses), hyperpigmentation of the skin, and gonadal dysfunction or infertility; occasional adverse effects include pain at injection site, dizziness, and headache; at high doses, occasional adverse affects include inappropriate behavior, confusion, somnolence, increased liver transaminases, increased bilirubin, and significant skin breakdown; rare adverse effects include hives, rash, and febrile reaction
Vincristine (Oncovin)
Mitotic inhibitor. This vinca alkaloid binds tubulin leading to its depolymerization, resulting in mitotic inhibition and metaphase arrest.
Adult
Pediatric
1-2 mg/m2/dose IV push; not to exceed 2 mg/dose; single dose used for specific courses of therapy in combination with doxorubicin and cyclophosphamide
May increase neurotoxicity when used with radiation; increased myelosuppression occurs with doxorubicin; acute pulmonary reaction may occur when taken concurrently with mitomycin-C
Documented hypersensitivity; IT administration (universally fatal)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include local ulceration if extravasated (vesicant), hair loss, and loss of deep tendon reflexes; occasional adverse effects include jaw pain, weakness, constipation, numbness, tingling, and clumsiness; rare adverse effects include paralytic ileus, ptosis, vocal cord paralysis, myelosuppression, CNS depression, SIADH, and seizure
Topotecan (Hycamtin)
Inhibits topoisomerase I, inhibiting DNA replication.
Adult
IV: Single-agent regimen: 1.5 mg/m2/d IV over 30 min days 1-5 of cycle, repeat every 3-4 wk for 4-6 cycles
PO: 2.3 mg/m2/d PO qd for days 1-5 of cycle; repeat q21d
Modify dose with bone marrow toxicity or grade III/IV diarrhea
Pediatric
1.2 mg/m2/dose IV qd on days 1-5 of each cycle
Concomitant administration with other antineoplastics may result in prolonged neutropenia and thrombocytopenia in addition to increased morbidity/mortality
Documented hypersensitivity; bone marrow suppression and renal function impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Side effects include myelosuppression, dermatitis, nausea, and vomiting; monitor bone marrow function
Colony-stimulating factors
These agents act as a hematopoietic growth factor that stimulates the development of granulocytes. They are used to treat or prevent neutropenia when 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 in the management of chronic neutropenia.
Filgrastim (G-CSF, Neupogen)
Promotes growth and differentiation of myeloid progenitor cells. May improve survival and function of granulocytes. In the posttransplant setting, administer until marrow recovery with absolute neutrophil count >10,000.
Adult
Pediatric
5-10 mcg/kg SC qd for 10-14 d
Start 24-36 h after last dose of chemotherapy, continue until absolute neutrophil count recovers to £ 5000
None reported
Documented hypersensitivity; allergy to yeast or Escherichia coli –derived proteins
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
Measure CBC count to determine end-point of therapy; avoid infectious contacts; seek care for fever, pain, or redness at injection site; occasional adverse effects include local irritation at the injection site, medullary bone pain, increased alkaline phosphatase, increased lactate dehydrogenase, increased uric acid, thrombocytopenia; rare adverse effects include allergies, low-grade fever, subclinical splenomegaly, exacerbation of preexisting skin rashes, alopecia, and cutaneous vasculitis
Chemoprotective agents
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, which is the ifosfamide and cyclophosphamide metabolite considered to be responsible for urotoxicity.
Mesna (Mesnex)
Interacts in the bladder with acrolein, a toxic metabolite of cyclophosphamide or ifosfamide to prevent hemorrhagic cystitis.
Adult
Pediatric
Usually 20-25% of ifosfamide or cyclophosphamide dose IV before chemotherapy and 3 h, 6 h, and 9 h after; in some instances, used as a continuous infusion
None reported
Documented hypersensitivity; thiol compounds
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
None specific; similar precautions for antineoplastic agents; common adverse effects include bad taste when PO; occasional adverse effects include nausea, vomiting, and stomach pain; rare adverse effects include headache, pain in arms, legs, and joints, fatigue, rash, transient hypotension, allergy, and diarrhea
More on Neuroblastoma |
| Overview: Neuroblastoma |
| Differential Diagnoses & Workup: Neuroblastoma |
 Treatment & Medication: Neuroblastoma |
| Follow-up: Neuroblastoma |
| Multimedia: Neuroblastoma |
| References |
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Further Reading
Keywords
neuroblastoma, sympathetic nervous system tumors of childhood, cancer, tumor, malignancy, neuroblasts, paraspinal dumbbell tumors, ganglioneuroblastoma, ganglioneuroma, hypertension, periorbital ecchymosis, thoracic neuroblastoma, cervical neuroblastoma, Horner syndrome, rubella, opsoclonus, myoclonus, Ewing sarcoma, stem cell transplantation, blueberry muffin baby, treatment, diagnosis
