Observation or Radiation Therapy and/or Chemotherapy and... | NCT00027846

NCT00027846

ID	Type	Description
CDR0000069086	Other Identifier	Clinical Trials.gov
NCI-2012-02431	Other Identifier	NCI
COG-ACNS0121	Other Identifier	Children's Oncology Group

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Determine the local control and pattern of failure in children with completely resected, differentiated, supratentorial localized ependymoma after initial surgical resection alone.
Determine the rate of complete resection with second surgery after chemotherapy in patients with initially incompletely resected localized ependymoma.
Determine the local control and pattern of failure in patients treated with conformal radiotherapy.
Determine the influence of histologic grade on the time to progression in patients after treatment with conformal radiotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to extent of prior surgical resection.

Group 1 (patients with supratentorial differentiated ependymoma who have undergone gross total resection and have no visible residual tumor): Patients undergo observation.
Group 2 (patients with supratentorial anaplastic ependymoma or infratentorial anaplastic or differentiated ependymoma who have undergone gross total resection or near total resection): Patients undergo conformal radiotherapy to the brain once daily 5 days a week for 6-6½ weeks.
Group 3 (patients with tumor of any histology or location who have undergone subtotal resection): Patients receive an initial course of chemotherapy comprising vincristine IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second surgery. Patients who have unresectable disease undergo conformal radiotherapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy.

Patients are followed every 4 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 250-350 patients will be accrued for this study within 5 years.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GTR1 Differentiated Histology Supratentorial (Group 1)	No Intervention	Patients undergo observation.
Radiation (Group 2)	Experimental	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks.	Radiation: radiation therapy
Sub-Total Resection Any Histology or Location (STR) (Group 3)	Experimental	Patients receive an initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy.	Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: etoposide Drug: vincristine sulfate Radiation: radiation therapy Drug: Mesna Procedure: therapeutic conventional surgery

Interventions

Name	Type	Description	Arm Group Labels	Other Names
filgrastim	Biological	Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously.	Sub-Total Resection Any Histology or Location (STR) (Group 3)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Event-free Survival	Event-free survival is calculated from the date of study enrollment to the date of disease progression, disease relapse, occurrence of second neoplasm, or death from any cause. The product-limit (Kaplan-Meier) estimate is for estimation of Event -free survival (EFS) probability at 5 years.	Up to 5 years after completion of study treatment

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival	Overall survival (OS) is measured from the date of study enrollment to the date to death. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability at 5 years.	Up to 5 years after completion of study treatment
Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy

Eligibility Module

Name	Affiliation	Role
Thomas E. Merchant, DO, PhD	St. Jude Children's Research Hospital	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham		Birmingham	Alabama	35294	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	GTR1 Differentiated Histology Supratentorial (Group 1)	Patients undergo observation.
FG001	Radiation (Group 2)	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	GTR1 Differentiated Histology Supratentorial (Group 1)	Patients undergo observation.
BG001	Radiation (Group 2)	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks
BG002	Sub-Total Resection Any Histology or Location (STR) (Group 3)	Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG00013 BG001281 BG00276 BG003

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00010.78(1.49 to 16.71) BG0015.58(1.01 to 21.01) BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0007 BG001114 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG00136 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG0001 BG00128 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Event-free Survival

Event-free survival is calculated from the date of study enrollment to the date of disease progression, disease relapse, occurrence of second neoplasm, or death from any cause. The product-limit (Kaplan-Meier) estimate is for estimation of Event -free survival (EFS) probability at 5 years.

The product-limit (Kaplan-Meier) estimate is for estimation of event-free survival probability at 5 years. All eligible patients in the study were included.

Posted

Number

95% Confidence Interval

Probability of EFS at 5 years

Up to 5 years after completion of study treatment

ID	Title	Description
OG000	GTR1 Differentiated Histology Supratentorial (Group 1)	Patients undergo observation.
OG001	Radiation (Group 2)	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks
OG002	Sub-Total Resection Any Histology or Location (STR) (Group 3)	Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient

Units	Counts
Participants	OG00011 OG001281 OG00264

Title

Denominators

Categories

Title	Measurements
	OG0000.614(0.33 to 0.90) OG0010.685(0.63 to 0.74) OG0020.372(0.25 to 0.50)

Secondary

Overall Survival

Overall survival (OS) is measured from the date of study enrollment to the date to death. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability at 5 years.

All eligible patients in the study were included. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability.

Posted

Number

95% Confidence Interval

Probability of OS at 5 years

Up to 5 years after completion of study treatment

ID	Title	Description
OG000	GTR1 Differentiated Histology Supratentorial (Group 1)	Patients undergo observation.
OG001	Radiation (Group 2)	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks
OG002	Sub-Total Resection Any Histology or Location (STR) (Group 3)	Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient

Secondary

Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy

The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment.

Of 64 eligible patients in this group, 25 patients after chemotherapy had the second surgery. Of 25 patients with second surgery after chemotherapy, 19 had a Gross-Total or Near-Total resection. 19/25=76%.

Posted

Number

95% Confidence Interval

percentage of participants

At the time of second surgery

ID	Title	Description
OG000	Sub-Total Resection Any Histology or Location (STR) (Group 3)	Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient

Secondary

Event-free Survival (EFS)

EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who had sub-total resection initially. The event-free survival (EFS) defined as the date of disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start date of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability.

Of 64 eligible patients who had initial subtotal resection, 5 patients were off-therapy prior to radiation therapy, and 4 patients had a disease progression prior to radiation therapy. There were 55 eligible patients included in the analysis. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability.

Posted

Number

95% Confidence Interval

Probability of EFS at 5 years

At 5 years since the time of radiation therapy.

ID	Title	Description
OG000	Differentiated Ependymoma	Differentiated ependymoma:tumor pathology by central review.
OG001	Anaplastic Ependymoma	Anaplastic ependymoma:tumor pathology by central review.

Units	Counts
Participants

Secondary

Event-free Survival (EFS)

EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who were treated with radiation therapy only. The event-free survival (EFS) defined as the time to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability at 5 years.

Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks.

Posted

Number

95% Confidence Interval

Probability of EFS at 5 years

At 5 years since the time of radiation therapy

ID	Title	Description
OG000	Differentiated Ependymoma	Differentiated ependymoma:tumor pathology by central review.
OG001	Anaplastic Ependymoma	Anaplastic ependymoma:tumor pathology by central review.

Units	Counts
Participants

Secondary

Local Control and Patterns of Failure

Documented and analyzed qualitatively and quantitatively.

All eligible patients in the study were included.

Posted

Number

Participant

Up to 5 years after completion of study treatment

ID	Title	Description
OG000	GTR1 Differentiated Histology Supratentorial (Group 1)	Patients undergo observation.
OG001	Radiation (Group 2)	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks
OG002	Sub-Total Resection Any Histology or Location (STR) (Group 3)	Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Radiation (Group 2)	Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks			38	281	52	281
EG001	Sub-Total Resection Any Histology or Location (STR) (Group 3)	Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC >1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient			55	64	27	64

Serious Adverse Events

Term	Organ System	Statistical Information
Inner ear/hearing	Ear and labyrinth disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hemoglobin (Hgb)	Blood and lymphatic system disorders	EG0000 events0 affected281 at risk EG00131 events28 affected64 at risk
Hemolysis (e.g., immune hemolytic anemia, drug related hemolysis, other)	Blood and lymphatic system disorders	EG0000 events0 affected281 at risk EG0012 events1 affected64 at risk
Leukocytes (total WBC)	Investigations	EG0004 events4 affected281 at risk EG00147 events40 affected64 at risk
Lymphopenia	Investigations	EG0008 events8 affected281 at risk EG00118 events15 affected64 at risk
Neutrophils/granulocytes (ANC/AGC)	Investigations	EG0006 events6 affected281 at risk EG00149 events40 affected64 at risk
Platelets	Investigations	EG0000 events0 affected281 at risk EG00128 events25 affected64 at risk
Transfusion: Platelets	Blood and lymphatic system disorders	EG0000 events0 affected281 at risk EG00111 events10 affected64 at risk
Transfusion: pRBCs	Blood and lymphatic system disorders	EG0001 events1 affected281 at risk EG00117 events14 affected64 at risk
Hypertension	Vascular disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Thrombosis/embolism	Vascular disorders	EG0000 events0 affected281 at risk EG0012 events1 affected64 at risk
Cardiovascular/General - Other (Specify)	Cardiac disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Partial thromboplastin time (PTT)	Investigations	EG0000 events0 affected281 at risk EG0012 events2 affected64 at risk
Constitutional Symptoms - Other (Specify)	General disorders	EG0001 events1 affected281 at risk EG0011 events1 affected64 at risk
Radiation dermatitis	Injury, poisoning and procedural complications	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Wound-infectious	Infections and infestations	EG0001 events1 affected281 at risk EG0013 events3 affected64 at risk
Anorexia	Metabolism and nutrition disorders	EG0002 events2 affected281 at risk EG0013 events3 affected64 at risk
Constipation	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Dehydration	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0012 events2 affected64 at risk
Diarrhea (without colostomy)	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0012 events2 affected64 at risk
Dysphagia, esophagitis, odynophagia (painful swallowing)	Gastrointestinal disorders	EG0001 events1 affected281 at risk EG0011 events1 affected64 at risk
Nausea	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Typhlitis (inflammation of cecum)	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Vomiting	Gastrointestinal disorders	EG0001 events1 affected281 at risk EG0014 events4 affected64 at risk
Gastrointestinal - Other (Specify)	Gastrointestinal disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	Vascular disorders	EG0002 events1 affected281 at risk EG0010 events0 affected64 at risk
Alkaline phosphatase	Investigations	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
SGOT (AST)	Investigations	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
SGPT (ALT)	Investigations	EG0001 events1 affected281 at risk EG0012 events1 affected64 at risk
Catheter-related infection	Infections and infestations	EG0001 events1 affected281 at risk EG0015 events3 affected64 at risk
Febrile neutropenia (fever unknown origin no clinically or microbiologically documented infection)	Blood and lymphatic system disorders	EG0001 events1 affected281 at risk EG00113 events12 affected64 at risk
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia	Infections and infestations	EG0002 events2 affected281 at risk EG00110 events10 affected64 at risk
Infection with unknown ANC	Infections and infestations	EG0001 events1 affected281 at risk EG0014 events3 affected64 at risk
Infection without neutropenia	Infections and infestations	EG0009 events9 affected281 at risk EG00113 events10 affected64 at risk
Amylase	Investigations	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hyperglycemia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hyperkalemia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hypernatremia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hypocalcemia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hypokalemia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0012 events2 affected64 at risk
Lipase	Investigations	EG0000 events0 affected281 at risk EG0019 events1 affected64 at risk
Ataxia (incoordination)	Nervous system disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Depressed level of consciousness	Nervous system disorders	EG0001 events1 affected281 at risk EG0011 events1 affected64 at risk
Extrapyramidal/involuntary movement/restlessness	Nervous system disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Hallucinations	Psychiatric disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Irritability (<3yrs of age)	General disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Mood alteration-anxiety, agitation	Psychiatric disorders	EG0001 events1 affected281 at risk EG0011 events1 affected64 at risk
Mood alteration-depression	Psychiatric disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Neuropathy - cranial	Nervous system disorders	EG0002 events2 affected281 at risk EG0010 events0 affected64 at risk
Neuropathy - motor	Nervous system disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Personality/behavioral	Psychiatric disorders	EG0002 events2 affected281 at risk EG0010 events0 affected64 at risk
Seizure(s)	Nervous system disorders	EG0003 events3 affected281 at risk EG0012 events2 affected64 at risk
Neurology - Other (Specify)	Nervous system disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Ocular/Visual - Other (Specify)	Eye disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Abdominal pain or cramping	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0011 events1 affected64 at risk
Headache	Nervous system disorders	EG0002 events2 affected281 at risk EG0011 events1 affected64 at risk
Apnea	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected281 at risk EG0014 events3 affected64 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected281 at risk EG0012 events2 affected64 at risk
Pulmonary - Other (Specify)	Respiratory, thoracic and mediastinal disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk
Incontinence	Renal and urinary disorders	EG0001 events1 affected281 at risk EG0010 events0 affected64 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Hemoglobin (Hgb)	Blood and lymphatic system disorders	EG0000 events0 affected281 at risk EG0015 events5 affected64 at risk
Leukocytes (total WBC)	Investigations	EG00018 events16 affected281 at risk EG0019 events8 affected64 at risk
Platelets	Investigations	EG0000 events0 affected281 at risk EG0017 events7 affected64 at risk
Fatigue (lethargy, malaise, asthenia)	General disorders	EG0000 events0 affected281 at risk EG0019 events6 affected64 at risk
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 109/L)	General disorders	EG0000 events0 affected281 at risk EG0016 events5 affected64 at risk
Weight loss	Investigations	EG0000 events0 affected281 at risk EG0014 events4 affected64 at risk
Alopecia	Skin and subcutaneous tissue disorders	EG00017 events17 affected281 at risk EG0010 events0 affected64 at risk
Anorexia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0015 events4 affected64 at risk
Constipation	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0016 events6 affected64 at risk
Nausea	Gastrointestinal disorders	EG0000 events0 affected281 at risk EG0016 events5 affected64 at risk
Vomiting	Gastrointestinal disorders	EG00019 events19 affected281 at risk EG0019 events7 affected64 at risk
SGOT (AST)	Investigations	EG0000 events0 affected281 at risk EG0016 events6 affected64 at risk
SGPT (ALT)	Investigations	EG0000 events0 affected281 at risk EG0018 events7 affected64 at risk
Hyperglycemia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0015 events5 affected64 at risk
Hypocalcemia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0015 events5 affected64 at risk
Hyponatremia	Metabolism and nutrition disorders	EG0000 events0 affected281 at risk EG0015 events4 affected64 at risk

Ancestor Terms

ID	Term
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors
D056831	Coordination Complexes
D009930	Organic Chemicals
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D017705	Lignans
D001593	Benzyl Compounds
D001555	Benzene Derivatives
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D054836	Indolizidines
D007212	Indolizines
D055585	Physical Phenomena
D000476	Alkanesulfonates
D017738	Alkanesulfonic Acids
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D013438	Sulfhydryl Compounds
D013457	Sulfur Compounds
D013451	Sulfonic Acids
D013456	Sulfur Acids

ID	Term
D001932	Brain Neoplasms
D016543	Central Nervous System Neoplasms

ID	Term
D009423	Nervous System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D000069585	Filgrastim
D016179	Granulocyte Colony-Stimulating Factor
D016190	Carboplatin
D003520	Cyclophosphamide
D005047	Etoposide
D011034	Podophyllotoxin
D014750	Vincristine
D011878	Radiotherapy
D011827	Radiation
D013812	Therapeutics
D015080	Mesna