Radiation Therapy Compared With Chemotherapy and Radiatio... | NCT00085098

NCT00085098

ID	Type	Description	Link
CDR0000367294	Other Identifier	Clinical Trials.gov
COG-ACNS0232	Other Identifier	Children's Oncology Group

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Primary

Compare event-free survival and overall survival of patients with newly diagnosed primary CNS germ cell tumor treated with conventional radiotherapy alone (regimen A) vs chemotherapy followed by tumor response-based radiotherapy (regimen B).

Secondary

Determine the complete response rate in patients treated with regimen B.
Determine the acute and subacute toxicity of regimen B in these patients.
Compare treatment-related morbidity, in terms of verbal learning and memory, executive functioning, and quality of life, in patients treated with these regimens.
Determine the prognostic value of baseline serum, lumbar, and intraventricular levels of human chorionic gonadotropin levels from patients treated with these regimens.
Determine the prognostic value of extent of disease (M+ vs modified M+ vs M0) on event-free survival and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor location (pineal vs suprasellar vs pineal + suprasellar or other), and disease stage (disseminated vs occult multi-focal vs localized). Patients are randomized to 1 of 2 treatment regimens.

All patients undergo an operative procedure (endoscopic biopsy, stereotactic biopsy, or open craniotomy) to confirm the diagnosis of pure germ cell germinoma followed by an intraoperative and perioperative staging evaluation.

Regimen A (radiotherapy only): Within 52 days of surgery, patients undergo standard-dose radiotherapy once daily on days 1-5 for approximately 5-6 weeks.
Regimen B (chemotherapy plus radiotherapy):
- Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Patients achieving a complete response (CR) proceed to reduced-dose radiotherapy. Patients with minimal residual disease (MRD), a partial response (PR), or stable disease (SD) receive chemotherapy courses 3 and 4 as outlined below. Patients with progressive disease undergo a second surgical procedure for biopsy and are restaged. Patients with a confirmed diagnosis of germ cell tumor with no change in tumor markers and no new lesions after restaging proceed to chemotherapy courses 3 and 4.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) subcutaneously or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses.

Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or progressive disease are restaged. Patients with a confirmed diagnosis of germ cell tumor after restaging undergo standard radiotherapy as in regimen A.

Reduced-dose radiotherapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiotherapy once daily on days 1-5 for 5 weeks.

Treatment in both regimens continues in the absence of unacceptable toxicity or in the event that a non-germinomatous germ cell tumor is detected.

Quality of life and neuropsychological function within the domains of intelligence, attention-concentration, memory, and executive functioning are assessed at 9, 30, and 60 months after diagnosis.

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

PROJECTED ACCRUAL: A total of 225 patients (approximately 112 per treatment regimen) will be accrued for this study within 5 years.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Regimen A (radiotherapy only)	Experimental	Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.	Radiation: radiation therapy
Regimen B (chemotherapy plus radiotherapy)	Experimental	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF), subcutaneous (SC) or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks	Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Radiation: radiation therapy

Name	Type	Description	Arm Group Labels	Other Names
filgrastim	Biological	Given by infusion or injection	Regimen B (chemotherapy plus radiotherapy)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Event-free Survival	Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up. QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause. Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol's primary objective. NOTE: Reported data are through May 2009 (see Caveats section).	Study enrollment until date of earliest qualifying event (QE), date last known to be QE-free if the patient is followed for less than three years and is QE-free at the time of analysis, or 3 years if the patient is QE-free at 3 years

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With a Response to Regimen B	To assess the complete response rate to pre-radiotherapy chemotherapy (Reg B only). Response was determined after completing 2-4 cycles of chemotherapy on Reg B. Complete Response (CR) is defined as disappearance of all target lesions.	5 years from beginning of treatment

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary CNS pure germ cell tumor
- Diagnosed within the past 31 days
Meets any 1 OR none (i.e., M0 [localized disease]) of the following staging criteria:
- M+ (disseminated disease)
  - Leptomeningeal or intraventricular metastases visualized on MRI scans of the brain and spine
  - Clumps of tumor cells on lumbar cerebrospinal fluid (CSF) cytology
  - Visible tumor studding the walls of the lateral or third ventricles noted during endoscopy or surgery
  - Primary tumor arising within the parenchyma of the brain, brainstem, or spinal cord
  - Measurable multi-focal tumors arising in both the pineal and suprasellar regions (i.e., multiple midline tumors)
  - Infiltrative, intra-axial extension on brain MRI > 1 cm beyond enhancing tumor
- Modified M+ (occult multi-focal disease)
  - M0 at diagnosis with a localized pineal region tumor with signs and symptoms of diabetes insipidus without measurable disease in the suprasellar region
Lumbar CSF assay meeting criteria for the following marker profiles:
- Serum and CSF beta human chorionic gonadotropin (β-HCG) ≤ 50 IU/dL
- Serum alpha fetoprotein (AFP) ≤ 10 IU/L AND ≤ institutional norm
- CSF AFP ≤ 2.0 IU/L AND ≤ institutional norm

PATIENT CHARACTERISTICS:

Age

3 to 25

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count > 1,000/mm^3
Platelet count > 100,000/mm^3 (transfusion independent)
Hemoglobin > 10.0 g/dL (transfusion allowed)

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times ULN

Renal

Creatinine adjusted according to age as follows*:
- No greater than 0.4 mg/dL (≤ 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male]) AND
Creatinine clearance OR radioisotope glomerular filtration rate > 70 mL/min

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Euthyroid (with or without levothyroxine sodium therapy) as determined by normal T4 ± thyroid-stimulating hormone levels*
Diabetes insipidus allowed provided patient is relatively stable on desmopressin acetate
Normal endogenous cortisol function*
Adequate antidiuretic hormone reserves* NOTE: *Unless receiving replacement therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Concurrent replacement hormones allowed (e.g., corticosteroids, levothyroxine sodium, and desmopressin acetate)

Radiotherapy

Not specified

Surgery

Prior surgery for germ cell tumor allowed

Other

No other prior therapy for germ cell tumor
Concurrent anticonvulsants allowed

Name	Affiliation	Role
Jeffrey C. Allen, MD	NYU Langone Health	Study Chair

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

ID	Title	Description
FG000	Regimen A (Radiotherapy Only)	Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.
FG001	Regimen B (Chemotherapy Plus Radiotherapy)

Courses 1,2:Patients (PTS) receive carboplatin IV over 1 hour on days 1-2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, PTS with complete response (CR) undergo low-dose radiation therapy 5 days a week for 5 weeks. PTS with minimal residual disease (MRD), a PR, or stable disease (SD) receive chemotherapy courses 3,4. Courses 3,4:PTS receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2-3 and filgrastim (G-CSF) subcutaneous (SC) or IV on day 4 continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. PTS achieving a CR or MRD proceed to reduced-dose radiotherapy. PTS with a partial response (PR), SD or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A.Reduced-dose radiation therapy: Within 6 weeks of starting course 4, PTS undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks.

Arm/Group Information

ID	Title	Description
BG000	Regimen A (Radiotherapy Only)	Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.
BG001	Regimen B (Chemotherapy Plus Radiotherapy)	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks
BG002	Total	Total of all reporting groups

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

Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up.

QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause.

Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol's primary objective.

NOTE: Reported data are through May 2009 (see Caveats section).

By protocol design, all eligible patients were considered in the evaluation of primary study aim. Two (2) patients were considered ineligible. All other patients (10 enrolled to regimen A and 12 enrolled to regimen B) are included in the evaluation for the primary outcome measure.

Posted

Number

participants

Study enrollment until date of earliest qualifying event (QE), date last known to be QE-free if the patient is followed for less than three years and is QE-free at the time of analysis, or 3 years if the patient is QE-free at 3 years

ID	Title	Description
OG000	Regimen A (Radiotherapy Only)	Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.
OG001	Regimen B (Chemotherapy Plus Radiotherapy)	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Units	Counts
Participants	OG00010 OG00112

Title

Denominators

Categories

Experienced a qualifying event

Title	Measurements
	OG0001(43 to 98) OG0011(54 to 99)

Event-free through 3 years of follow-up

Title	Measurements
	OG000

Secondary

Number of Participants With a Response to Regimen B

To assess the complete response rate to pre-radiotherapy chemotherapy (Reg B only). Response was determined after completing 2-4 cycles of chemotherapy on Reg B. Complete Response (CR) is defined as disappearance of all target lesions.

Patients who were treated in Regimen B and had at least one response assessment are included in this analysis. One patient in Regimen B withdrew from the pre-Radiotherapy chemotherapy and did not have any response assessment were not included for the response analysis.

Posted

Count of Participants

Participants

5 years from beginning of treatment

ID	Title	Description
OG000	Regimen B (Chemotherapy Plus Radiotherapy)	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks.

Secondary

Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. The list of toxicities of interest include Anemia or Febrile Neutropenia; Nausea or Vomiting; Infections and Infestations; Neutrophil or White blood count decrease; and Hypokalemia or Hyponatremia

Patients who received any pre-radiotherapy chemotherapy in Regimen B

Posted

Count of Participants

Participants

From the beginning of treatment, assessed up to 5 years

ID	Title	Description
OG000	Regimen B (Chemotherapy Plus Radiotherapy)	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF), subcutaneous (SC) or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Secondary

Quality of Life (QOL) and Neurocognitive Assessment (NP)

The primary endpoints for QOL and NP assessments will be the global scale value from each of these instruments at the two-year time point. Analyses of subscales (if they exist) and of assessments at other times will be of secondary interest. It is assumed that scale values are standardized to a reference normal population. The scores range from 0 to 100 with higher score reflecting better QoL or neurocognitive assessment.

All eligible patients who also successfully completed therapy and were assessed for quality of life and neurocognitive outcome.

Posted

Mean

Standard Deviation

Scores on a scale

2 years from beginning of treatment

ID	Title	Description
OG000	Regimen A (Radiotherapy Only)	Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks. radiation therapy: Patients undergo radiotherapy 5 days a week
OG001	Regimen B (Chemotherapy Plus Radiotherapy)	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

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	Regimen A (Radiotherapy Only)	Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.			0	10	4	10
EG001	Regimen B (Chemotherapy Plus Radiotherapy)	Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses. Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below. Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF) SC or IV beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or PD are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks			0	12	11	12

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected12 at risk
Anaphylaxis	Immune system disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected12 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected12 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected12 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected12 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected12 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected12 at risk
GGT increased	Investigations	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected12 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected12 at risk
Hypernatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected12 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0012 events2 affected12 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected10 at risk EG0013 events3 affected12 at risk
"Infections and infestations - Other, specify"	Infections and infestations	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected12 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0003 events3 affected10 at risk EG0014 events4 affected12 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected12 at risk
"Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify"	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected12 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0000 events0 affected10 at risk EG0019 events9 affected12 at risk
Peripheral motor neuropathy	Nervous system disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected12 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0000 events0 affected10 at risk EG0017 events7 affected12 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected10 at risk EG0012 events2 affected12 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0001 events1 affected10 at risk EG0015 events5 affected12 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
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D013812	Therapeutics

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
D002945	Cisplatin
D003520	Cyclophosphamide
D005047	Etoposide
C061400	etoposide phosphate
D011878	Radiotherapy