N2001-02: I-MIBG With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

• Sponsor: Children's Hospital Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT00253435
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 50
• Locations: 15
• Arm: 1
• Duration (Months): 99
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more tumor cells are killed. Giving radiation therapy after an autologous peripheral stem cell or bone marrow transplant may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine together with combination chemotherapy and radiation therapy works in treating patients who are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or refractory neuroblastoma.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Biological: Filgrastim; Drug: Carboplatin; Drug: Etoposide; Drug: Melphalan; Procedure: Peripheral blood stem cell infusion; Radiation: 131I-MIBG; Radiation: Radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with relapsed or refractory neuroblastoma treated with iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and combination chemotherapy comprising carboplatin, etoposide, and melphalan followed by autologous bone marrow or peripheral blood stem cell transplantation and radiotherapy.

Secondary

• Determine the hematopoietic and nonhematopoietic toxicity of this regimen in these patients.

• Determine the tumor self-absorbed radiation dose (TSARD) in patients with measurable soft tissue lesions treated with this regimen.

• Correlate the TSARD with tumor response in patients with measurable residual soft tissue disease treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (poor-risk group [mixed or no response to induction therapy or progression during or after induction therapy] vs good-risk group [partial response after 4 courses of induction therapy]) and kidney function at study entry (glomerular filtration rate [GFR] ≥ 100 mL/min vs GFR 60-99 mL/min)

• Stem cell harvest: Patients undergo a peripheral blood stem cell harvest or bone marrow harvest provided they have an adequate number of cells available. At least 2 weeks later, patients proceed to iodine I 131 metaiodobenzylguanidine (^131I-MIBG) and combination chemotherapy.

• 131I-MIBG and combination chemotherapy: Patients receive ^131I-MIBG IV over 2 hours on day -21, carboplatin IV continuously on days -7 to -4, etoposide IV continuously on days -7 to -4, and melphalan IV over 1 hour on days -7 to -5.

• Stem cell infusion and filgrastim (G-CSF): Three days after completion of chemotherapy, patients undergo transplantation of either stem cells or bone marrow on day 0. Patients also receive G-CSF subcutaneously or IV over 1 hour once daily beginning on day 0 and continuing until blood counts return to normal.

• Radiotherapy: Once blood counts return to normal, patients undergo radiotherapy to primary and metastatic sites that have not received previous irradiation over 12 days beginning after day 42.

After completion of study treatment, patients are followed for 2 years and then periodically thereafter.

PROJECTED ACCRUAL: Approximately 50 patients (40 low-risk patients and 8-10 high-risk patients) will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: All the patients enrolled in the study This is a single arm study. The following description applies to all the patients who are enrolled in the study: On Day -21, patients receive 131I-MIBG infusion. On Day -7, Day -6, Day -5, patients receive Carboplatin, Etoposide, Melphalan. On Day -4, patients receive Carboplatin, Etoposide. On Day -3, Day -2, Day -1, patients rest. On Day 0, patients receive peripheral blood stem cell infusion. Dosing of Carboplatin, Etoposide and Melphalan is based upon whole body dosimetry (cGy) estimates. Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0. Local radiation therapy is to be given to previously non-irradiated primary and metastatic sites of disease.

Biological: Filgrastim; Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0. The first dose should begin four hours after the stem cell infusion is completed. Filgrastim will continue daily until the ANC >=1500/uL for three consecutive days.; Other Names: G-CSF ; Drug: Carboplatin; The carboplatin will be administered as a continuous IV infusion Day - 7 through Day - 4, with dosing based upon pretreatment GFR levels. The carboplatin should be diluted to a concentration of 0.3 mg/ml in D5W 0.45NS and infused concomitantly with etoposide through the same central venous catheter using a "Y" connector; a controlled rate infusion pump is used for each arm of the "Y".; Other Names: cis-diammine; Paraplatin; Paraplatin-AQ ; Drug: Etoposide; The etoposide shall be administered day -7 through day -4 via continuous intravenous infusion over 96 hours. For patients with a corrected GFR >= 100 ml/min/1.72 m^2, a dose of 300 mg/m^2/day (10 mg/kg/day if child is < 12 kg) shall be given. For patients with a corrected GFR 60-99 ml/min/1.72 m^2, the etoposide will be administered at a dose of 160 mg/m^2/day (5.3 mg/kg/day). The etoposide will be diluted in D5W 0.45%NS at a concentration of < 0.4 mg/ml. Etoposide should not be mixed with carboplatin, but administered using a Y-connector.; Other Names: VP-16; Etopophos ; Drug: Melphalan; For patients in either the normal GFR strata (>=100 ml/min/1.73 m^2), or reduced GFR strata (60-99 ml/min/1.73m^2), melphalan shall be administered at a dose of 60 mg/m^2/day (2 mg/kg/day if child is < 12 kg) on day -7, -6, and -5 of study. The melphalan should be infused at a rate of less than 10 mg/minute, and should complete within 1 hour of reconstitution each day. The melphalan should be diluted in 0.9% NaCl at a concentration < 2 mg/ml. The total dosage of melphalan to be administered will be 180 mg/m^2.; Other Names: L-phenylalanine mustard; L-PAM; Alkeran; Sarcolysin ; Procedure: Peripheral blood stem cell infusion; Stem cells or marrow will be infused on day 0 of study therapy. Where the DMSO concentration in the stem cell product would exceed accepted level for infusion within a 24 hour period, stem cell products may be infused over two days to meet this standard. For purged PBSC: A minimum of 2.0 x 10^6 viable CD34+ cells/kg must be available. For unpurged PBSC, a minimum of 2.0 x 10^6 viable CD34+ cells/kg must be available. Having a back-up of 2.0 x 10^6 viable CD34+ cells/kg purged or unpurged PBSC is recommended but not required. For purged bone marrow, a minimum of 1.5 x10^8 mononuclear cells/kg must be available.; Radiation: 131I-MIBG; Therapeutic 131I MIBG will be synthesized by Draximage Canada.with specific activity between 15 and 25mCi/ml. Radiopurity will be initially determined by Draximage, prior to shipment to participating centers. Free radioiodide content must then be rechecked at the treating center prior to infusion using HPLC or Sep-Pac methodology.; Other Names: Iobenguane I 131 ; Radiation: Radiation therapy; Local irradiation is to be given to previously non-irradiated primary and metastatic sites of disease. Local irradiation should not start till the patient is medically stable, has an ANC > 1000/uL, platelets > 30,000 / uL, and is > 42 days post transplant. Recommended radiation guidelines consist of 2160 cGy total, given over 12 days using a single 180 cGy fraction/day. Any delay in local radiation that would extend treatment beyond day +84 should be discussed with the study chair. Local radiation will be administered at a participating NANT member site.

Outcome Measures

Primary Outcome Measures

1. Response (Complete Response, Very Good Partial Response, and Partial Response) at 60-days Post Stem Cell Infusion [Response assessed 60 days post stem cell infusion]

   Tumor response based on evaluation performed on day 60 or at the time of disease progression/recurrence or start of another treatment - whichever comes first. Such evaluations will include 123I-MIBG scan, CT/MRI, urine catecholamine measurement, and bone marrow analysis (for those with marrow disease at study entry).

Secondary Outcome Measures

1. Event-free Survival (EFS) at 3 Years [3 years since start of treatment]

   EFS will be measured from start of treatment until progression, death or start of another treatment - whichever comes first. We report the estimated probability of EFS at 3 years.

2. Engraftment DLT [From treatment start until 60 days post stem cell infusion]

   • Engraftment toxicity: delayed engraftment and/or failure to engraft defined as: neutrophils (ANC) < 500/μL by day 28 post transplant, or platelets < 20,000 /μL by day 56 post transplant, or if additional stem cells are required to be infused for any medical reason prior to initial engraftment of neutrophils or platelets.

3. Dose Limiting Veno-occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome SOS [Between start of MIBG treatment and 60 days post stem cell infusion]

   Dose limiting veno-occlusive disease (VOD) defined as: the presence of hepatomegaly with right upper quadrant tenderness and an elevation of total bilirubin > grade 1, PLUS the presence of grade 3 abnormalities of any ONE of the following: total bilirubin, hypoalbuminemia, weight gain, or hypoxia without other attribution

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 29 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed or refractory neuroblastoma

• Histologically confirmed and/or demonstration of tumor cells in bone marrow with elevated urinary catecholamine metabolites

• High-risk neuroblastoma must meet one of the following:

• Progressive disease prior to or after completion of induction therapy

• Mixed response or no response after completion of 4 courses of induction therapy

• Partial response after 4 courses of induction therapy allowed provided no prior participation in COG-A3973 or other phase III COG trials

• Measurable disease, defined as at least one metaiodobenzylguanidine (MIBG)-avid target lesion determined by diagnostic MIBG scan within 6 weeks of study entry (tumor sites that have received local irradiation within 3 months of study entry are not considered target lesions)

PATIENT CHARACTERISTICS:

Performance status

• Lansky 60-100% OR

• Karnofsky 60-100%

Life expectancy

• At least 2 months

Hematopoietic

• Hemoglobin ≥ 10 g/dL

• Absolute neutrophil count ≥ 750/mm^3

• Platelet count ≥ 50,000/mm^{3 (if no marrow involvement by morphologic exam/no transfusion allowed) (> 20,000/mm}3 if metastatic tumor involvement of marrow by morphologic exam/transfusion allowed)

Hepatic

• Bilirubin < 1.3 mg/dL

• SGOT and SGPT < 5 times normal

• Hepatitis B surface antigen negative

• Hepatitis C negative

Renal

• Glomerular filtration rate or creatinine clearance ≥ 60 ml/min

• Creatinine ≤ 1.5 times normal for age as follows:

• 0.8 mg/dL (for patients ≤ 5 years of age)

• 1.0 mg/dL (for patients 6 to 10 years of age)

• 1.2 mg/dL (for patients 11 to 15 years of age)

• 1.5 mg/dL (for patients > 15 years of age)

Cardiovascular

• Ejection fraction ≥ 55% by echocardiogram or radionuclide MUGA OR

• Fractional shortening ≥ 27% by echocardiogram

Pulmonary

• Normal lung function defined as no dyspnea at rest and no oxygen requirement OR measured oxygen saturation > 93% on room air

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No disease of any major organ system that would preclude study compliance

• No concurrent hemodialysis

• No active infection requiring IV antivirals, antibiotics, or antifungals (patients on antifungal therapy are eligible provided they are culture- and biopsy-negative in suspected residual radiographic lesions)

• Patient weight within limits to receive ≤ maximum total allowable dose of ^131I-MIBG

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior myeloablative transplantation

• Prior submyeloablative transplantation allowed at discretion of principal investigator

• More than 3 weeks since prior biologic therapy

Chemotherapy

• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for mitomycin C or nitrosoureas)

• No prior melphalan therapy with a total dose of > 100 mg/m^2

Radiotherapy

• See Disease Characteristics

• At least 6 weeks since prior radiotherapy (6 months for craniospinal or whole lung radiotherapy)

• No prior total body irradiation

• No prior iodine I 131 MIBG (^131I-MIBG)

• No prior total abdominal or whole liver radiotherapy

• No prior local radiotherapy, including any of the following:

• 1200 cGy to more than 33% of both kidneys (patient must have at least one kidney that has not exceeded the dose/volume of radiation listed)

• 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver

Other

• Recovered from all prior therapy

• No medications with a potential interference of ^131I-MIBG uptake 1 week before and 2 weeks after completion of ^131I-MIBG

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027-0700
2	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California	United States	94304
3	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94143
4	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia	United States	30322
5	University of Chicago Comer Children's Hospital	Chicago	Illinois	United States	60637
6	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
7	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-0286
8	Morgan Stanley Children's Hospital of New York-Presbyterian	New York	New York	United States	10032
9	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-4318
11	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
12	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Houston	Texas	United States	77030-2399
13	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
14	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
15	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• Children's Hospital Los Angeles
• National Cancer Institute (NCI)

Investigators

• Study Chair: Gregory Yanik, MD, University of Michigan Rogel Cancer Center
• Principal Investigator: Katherine K. Matthay, MD, University of California, San Francisco
• Principal Investigator: John M. Maris, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nant Operations Center, NANT Operations Center, Children's Hospital Los Angeles
• ClinicalTrials.gov Identifier: NCT00253435
• Other Study ID Numbers: CDR0000450148; P01CA081403; N2001-02
• First Posted: Nov 15, 2005
• Last Update Posted: Aug 24, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Nant Operations Center, NANT Operations Center, Children's Hospital Los Angeles: recurrent neuroblastoma
• Additional relevant MeSH terms: Neuroblastoma; Carboplatin; Etoposide; Melphalan

Study Results

Participant Flow

Recruitment Details	Opened to accrual on 12/10/04 & closed to accrual on 07/21/10; suspended 6 times for amendments. Opened at 12 NANT institutions. 1st patient started on treatment on 03/11/05. 50 patients enrolled; all eligible & evaluable for toxicity. 49 patients were evaluable for response.

Arm/Group Title	Poor Risk Patients	Good Risk Patients
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.	Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.
Period Title: Overall Study
STARTED	42	8
1st Interim Analysis	15	8
2nd Interim Analysis	10	0
3rd Interim Analysis	10	0
COMPLETED	42	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Poor Risk Patients	Good Risk Patients	Total
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.	Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.	Total of all reporting groups
Overall Participants	42	8	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	6.0	7.7	6.0
Sex: Female, Male (Count of Participants)
Female	10 23.8%	2 25%	12 24%
Male	32 76.2%	6 75%	38 76%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 9.5%	3 37.5%	7 14%
Not Hispanic or Latino	38 90.5%	5 62.5%	43 86%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 7.1%	0 0%	3 6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 9.5%	0 0%	4 8%
White	33 78.6%	8 100%	41 82%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.8%	0 0%	2 4%
GFR Status (participants) [Number]
Normal GFR	30 71.4%	7 87.5%	37 74%
Low GFR	12 28.6%	1 12.5%	13 26%

Outcome Measures

1. Primary Outcome

Title	Response (Complete Response, Very Good Partial Response, and Partial Response) at 60-days Post Stem Cell Infusion
Description	Tumor response based on evaluation performed on day 60 or at the time of disease progression/recurrence or start of another treatment - whichever comes first. Such evaluations will include 123I-MIBG scan, CT/MRI, urine catecholamine measurement, and bone marrow analysis (for those with marrow disease at study entry).
Time Frame	Response assessed 60 days post stem cell infusion

Outcome Measure Data

Analysis Population Description

One patient in the Poor Risk Cohort underwent surgery for resection (of his only measureable lesion) prior to post-treatment assessment and is not evaluable for response.

Arm/Group Title	Poor Risk Patients	Good Risk Patients
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.	Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.
Measure Participants	41	8
Number [participants]	4 9.5%	3 37.5%

2. Secondary Outcome

Title	Event-free Survival (EFS) at 3 Years
Description	EFS will be measured from start of treatment until progression, death or start of another treatment - whichever comes first. We report the estimated probability of EFS at 3 years.
Time Frame	3 years since start of treatment

Outcome Measure Data

Analysis Population Description

Estimated probability of 3-year progression free survival for all patients enrolled in each risk group.

Arm/Group Title	Poor Risk Patients	Good Risk Patients
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.	Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.
Measure Participants	42	8
Number [Estimated probability]	0.20	0.38

3. Secondary Outcome

Title	Engraftment DLT
Description	• Engraftment toxicity: delayed engraftment and/or failure to engraft defined as: neutrophils (ANC) < 500/μL by day 28 post transplant, or platelets < 20,000 /μL by day 56 post transplant, or if additional stem cells are required to be infused for any medical reason prior to initial engraftment of neutrophils or platelets.
Time Frame	From treatment start until 60 days post stem cell infusion

Outcome Measure Data

Analysis Population Description

All patients who began treatment

Arm/Group Title	Poor Risk Patients	Good Risk Patients
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.	Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.
Measure Participants	42	8
Number [participants]	2 4.8%	1 12.5%

4. Secondary Outcome

Title	Dose Limiting Veno-occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome SOS
Description	Dose limiting veno-occlusive disease (VOD) defined as: the presence of hepatomegaly with right upper quadrant tenderness and an elevation of total bilirubin > grade 1, PLUS the presence of grade 3 abnormalities of any ONE of the following: total bilirubin, hypoalbuminemia, weight gain, or hypoxia without other attribution
Time Frame	Between start of MIBG treatment and 60 days post stem cell infusion

Outcome Measure Data

Analysis Population Description

All patients who began treatment

Arm/Group Title	Poor Risk Patients	Good Risk Patients
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.	Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.
Measure Participants	42	8
Number [participants]	6 14.3%	0 0%

Adverse Events

Arm/Group Title	Poor Risk Patients		Good Risk Patients
Arm/Group Description	Poor risk patients are those who experienced a Minor response (MR) or No Response (NR) to induction therapy or progressive disease (PD) during or following induction.		Good risk patients are those who experienced a Partial Response (PR) following 4 cycles of induction.
All Cause Mortality
	Poor Risk Patients		Good Risk Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Poor Risk Patients		Good Risk Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/42 (28.6%)		3/8 (37.5%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (DELAYED PLATELET ENGRAFTMENT)	1/42 (2.4%)	1	0/8 (0%)	0
Blood/Bone Marrow - Other (INFUSION OF BACKUP STEM CELLS)	1/42 (2.4%)	1	0/8 (0%)	0
Gastrointestinal disorders
Vomiting	1/42 (2.4%)	1	0/8 (0%)	0
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	2/42 (4.8%)	2	0/8 (0%)	0
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other (HEPATOMEGALY)	1/42 (2.4%)	1	0/8 (0%)	0
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Blood)	2/42 (4.8%)	3	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Catheter-related)	1/42 (2.4%)	1	1/8 (12.5%)	1
Investigations
Bilirubin (hyperbilirubinemia)	5/42 (11.9%)	5	0/8 (0%)	0
Neutrophils/granulocytes (ANC/AGC)	0/42 (0%)	0	1/8 (12.5%)	1
Platelets	1/42 (2.4%)	1	1/8 (12.5%)	1
Weight gain	5/42 (11.9%)	5	0/8 (0%)	0
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	2/42 (4.8%)	2	0/8 (0%)	0
Nervous system disorders
Pain (Head/headache)	1/42 (2.4%)	1	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/42 (0%)	0	1/8 (12.5%)	1
Dyspnea (shortness of breath)	1/42 (2.4%)	1	0/8 (0%)	0
Hypoxia	4/42 (9.5%)	4	1/8 (12.5%)	1
Vascular disorders
Hypotension	1/42 (2.4%)	1	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Poor Risk Patients		Good Risk Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/42 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (DELAYED ENGRAFTMENT ANC)	0/42 (0%)	0	1/8 (12.5%)	1
Blood/Bone Marrow - Other (INFUSION OF BACKUP SC FOR DELAYED ENGRAFTMENT)	0/42 (0%)	0	1/8 (12.5%)	1
Febrile neutropenia (fever of unknown origin)	31/42 (73.8%)	31	6/8 (75%)	6
Hemoglobin	40/42 (95.2%)	40	7/8 (87.5%)	7
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)	1/42 (2.4%)	1	0/8 (0%)	0
Lymphatics - Other (CAPILLARY LEAK)	1/42 (2.4%)	1	0/8 (0%)	0
Lymphatics - Other (GENERALIZED EDEMA)	1/42 (2.4%)	1	0/8 (0%)	0
Cardiac disorders
Cardiac Arrhythmia - Other (MURMUR)	1/42 (2.4%)	1	0/8 (0%)	0
Cardiac Arrhythmia - Other (SINUS TACHYCARDIA)	1/42 (2.4%)	1	0/8 (0%)	0
Cardiac General - Other (SYSTOLIC MURMUR)	1/42 (2.4%)	1	0/8 (0%)	0
Supraventricular and nodal arrhythmia (Atrial tachycardia/Paroxysmal Atrial Tachycardia)	1/42 (2.4%)	1	0/8 (0%)	0
Supraventricular and nodal arrhythmia (Sinus tachycardia)	11/42 (26.2%)	11	0/8 (0%)	0
Ventricular arrhythmia (Ventricular arrhythmia NOS)	0/42 (0%)	0	1/8 (12.5%)	1
Ear and labyrinth disorders
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	1/42 (2.4%)	1	1/8 (12.5%)	1
Hearing: patients without baseline audiogram and not enrolled in a monitoring program	1/42 (2.4%)	1	0/8 (0%)	0
Otitis, middle ear (non-infectious)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Middle ear)	1/42 (2.4%)	1	0/8 (0%)	0
Endocrine disorders
Endocrine - Other (TSH)	1/42 (2.4%)	1	0/8 (0%)	0
Thyroid function, high (hyperthyroidism, thyrotoxicosis)	1/42 (2.4%)	1	0/8 (0%)	0
Eye disorders
Ocular/Visual - Other (BILATERAL CONJUNCTIVAL HEMORRHAGE)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Eye)	1/42 (2.4%)	1	0/8 (0%)	0
Gastrointestinal disorders
Ascites (non-malignant)	5/42 (11.9%)	5	0/8 (0%)	0
Cheilitis	4/42 (9.5%)	4	0/8 (0%)	0
Constipation	8/42 (19%)	8	2/8 (25%)	2
Dental: teeth	1/42 (2.4%)	1	0/8 (0%)	0
Diarrhea	32/42 (76.2%)	32	4/8 (50%)	4
Distension/bloating, abdominal	5/42 (11.9%)	5	0/8 (0%)	0
Dry mouth/salivary gland (xerostomia)	1/42 (2.4%)	1	0/8 (0%)	0
Dysphagia (difficulty swallowing)	2/42 (4.8%)	2	0/8 (0%)	0
Gastrointestinal - Other (HICCUPS)	1/42 (2.4%)	1	0/8 (0%)	0
Gastrointestinal - Other (LOOSE TEETH)	1/42 (2.4%)	1	0/8 (0%)	0
Gastrointestinal - Other (REFLUX)	1/42 (2.4%)	1	0/8 (0%)	0
Heartburn/dyspepsia	3/42 (7.1%)	3	0/8 (0%)	0
Hemorrhage, GI (Lower GI NOS)	2/42 (4.8%)	2	0/8 (0%)	0
Hemorrhage, GI (Oral cavity)	2/42 (4.8%)	2	1/8 (12.5%)	1
Hemorrhage, GI (Stomach)	1/42 (2.4%)	1	0/8 (0%)	0
Hemorrhage, GI (Upper GI NOS)	5/42 (11.9%)	5	0/8 (0%)	0
Mucositis/stomatitis (clinical exam) (Anus)	1/42 (2.4%)	1	0/8 (0%)	0
Mucositis/stomatitis (clinical exam) (Esophagus)	1/42 (2.4%)	1	0/8 (0%)	0
Mucositis/stomatitis (clinical exam) (Oral cavity)	29/42 (69%)	29	5/8 (62.5%)	5
Mucositis/stomatitis (clinical exam) (Rectum)	1/42 (2.4%)	1	0/8 (0%)	0
Mucositis/stomatitis (functional/symptomatic) (Large bowel)	1/42 (2.4%)	1	0/8 (0%)	0
Mucositis/stomatitis (functional/symptomatic) (Oral cavity)	14/42 (33.3%)	14	4/8 (50%)	4
Mucositis/stomatitis (functional/symptomatic) (Small bowel)	1/42 (2.4%)	1	0/8 (0%)	0
Mucositis/stomatitis (functional/symptomatic) (Stomach)	1/42 (2.4%)	1	0/8 (0%)	0
Nausea	32/42 (76.2%)	32	5/8 (62.5%)	5
Obstruction, GI (Small bowel NOS)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Abdomen NOS)	20/42 (47.6%)	20	3/8 (37.5%)	3
Pain (Esophagus)	1/42 (2.4%)	1	1/8 (12.5%)	1
Pain (Oral cavity)	19/42 (45.2%)	19	3/8 (37.5%)	3
Pain (Oral-gums)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Rectum)	1/42 (2.4%)	1	1/8 (12.5%)	1
Pain (Stomach)	2/42 (4.8%)	2	1/8 (12.5%)	1
Salivary gland changes/saliva	1/42 (2.4%)	1	0/8 (0%)	0
Typhlitis (cecal inflammation)	1/42 (2.4%)	1	0/8 (0%)	0
Vomiting	33/42 (78.6%)	33	7/8 (87.5%)	7
General disorders
Constitutional Symptoms - Other (BRITTLE HAIR)	1/42 (2.4%)	1	0/8 (0%)	0
Constitutional Symptoms - Other (RHINORRHEA)	1/42 (2.4%)	1	0/8 (0%)	0
Edema:head and neck	5/42 (11.9%)	5	2/8 (25%)	2
Edema:limb	3/42 (7.1%)	3	0/8 (0%)	0
Edema:trunk/genital	2/42 (4.8%)	2	1/8 (12.5%)	1
Fatigue (asthenia, lethargy, malaise)	12/42 (28.6%)	12	0/8 (0%)	0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	16/42 (38.1%)	16	2/8 (25%)	2
Irritability (children <3 years of age)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Chest/thorax NOS)	2/42 (4.8%)	2	0/8 (0%)	0
Pain (Face)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Pain NOS)	1/42 (2.4%)	1	0/8 (0%)	0
Pain - Other (BROVIAC SITE)	1/42 (2.4%)	1	0/8 (0%)	0
Pain - Other (CVC SITE)	1/42 (2.4%)	1	0/8 (0%)	0
Pain - Other (GENERAL (NOS))	2/42 (4.8%)	2	0/8 (0%)	0
Pain - Other (MOUTH PAIN)	1/42 (2.4%)	1	0/8 (0%)	0
Pain - Other (MUCOSITIS)	1/42 (2.4%)	1	0/8 (0%)	0
Pain - Other (OROPHANRIX)	0/42 (0%)	0	1/8 (12.5%)	1
Pain - Other (PAROTID GLAND)	1/42 (2.4%)	1	0/8 (0%)	0
Pain - Other (WHOLE BODY)	1/42 (2.4%)	1	0/8 (0%)	0
Rigors/chills	2/42 (4.8%)	2	0/8 (0%)	0
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other (CHOLANGITIS)	1/42 (2.4%)	1	0/8 (0%)	0
Liver dysfunction/failure (clinical)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Liver)	1/42 (2.4%)	1	0/8 (0%)	0
Portal vein flow	3/42 (7.1%)	3	0/8 (0%)	0
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	2/42 (4.8%)	2	0/8 (0%)	0
Cytokine release syndrome/acute infusion reaction	1/42 (2.4%)	1	0/8 (0%)	0
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) (Blood)	5/42 (11.9%)	5	2/8 (25%)	2
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) (Catheter-related)	2/42 (4.8%)	2	1/8 (12.5%)	1
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) (Lung (pneumonia))	2/42 (4.8%)	2	0/8 (0%)	0
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) (Mucosa)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) (Sinus)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) (Skin (cellulitis))	1/42 (2.4%)	1	1/8 (12.5%)	1
Infection - Other (ASPERGILLUS OF MOUTH)	1/42 (2.4%)	1	0/8 (0%)	0
Infection - Other (L-PRESEPTAL CELLULITIS)	1/42 (2.4%)	1	0/8 (0%)	0
Infection - Other (ORAL CANDIDA)	1/42 (2.4%)	1	0/8 (0%)	0
Infection - Other (PERIRECTAL CELLULITIS)	1/42 (2.4%)	1	0/8 (0%)	0
Infection - Other (URINE + FOR CYTOMEGALOVIRUS)	1/42 (2.4%)	1	0/8 (0%)	0
Infection - Other (VARICELLA)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Blood)	6/42 (14.3%)	6	1/8 (12.5%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils (Bronchus)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Catheter-related)	3/42 (7.1%)	3	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Colon)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Lung (pneumonia))	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Oral cavity-gums (gingivitis))	2/42 (4.8%)	2	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Sinus)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Small bowel NOS)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with normal ANC or Grade 1 or 2 neutrophils (Upper airway NOS)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with unknown ANC (Catheter-related)	1/42 (2.4%)	1	0/8 (0%)	0
Infection with unknown ANC (Skin (cellulitis))	0/42 (0%)	0	1/8 (12.5%)	1
Opportunistic infection associated with >=Grade 2 Lymphopenia	1/42 (2.4%)	1	0/8 (0%)	0
Injury, poisoning and procedural complications
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	2/42 (4.8%)	2	0/8 (0%)	0
Rash: dermatitis associated with radiation (Chemoradiation)	2/42 (4.8%)	2	0/8 (0%)	0
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	34/42 (81%)	34	8/8 (100%)	8
AST, SGOT(serum glutamic oxaloacetic transaminase)	36/42 (85.7%)	36	8/8 (100%)	8
Alkaline phosphatase	8/42 (19%)	8	2/8 (25%)	2
Bilirubin (hyperbilirubinemia)	10/42 (23.8%)	10	1/8 (12.5%)	1
Cholesterol, serum-high (hypercholesteremia)	1/42 (2.4%)	1	0/8 (0%)	0
Creatinine	7/42 (16.7%)	7	0/8 (0%)	0
Fibrinogen	1/42 (2.4%)	1	0/8 (0%)	0
GGT (gamma-Glutamyl transpeptidase)	15/42 (35.7%)	15	0/8 (0%)	0
INR (International Normalized Ratio of prothrombin time)	7/42 (16.7%)	7	1/8 (12.5%)	1
Leukocytes (total WBC)	38/42 (90.5%)	38	8/8 (100%)	8
Lymphopenia	30/42 (71.4%)	30	5/8 (62.5%)	5
Metabolic/Laboratory - Other (CHLORIDE)	1/42 (2.4%)	1	0/8 (0%)	0
Metabolic/Laboratory - Other (DECREASED TOTAL PROTEIN)	0/42 (0%)	0	1/8 (12.5%)	1
Metabolic/Laboratory - Other (HYPERCHLOREMIA)	0/42 (0%)	0	1/8 (12.5%)	1
Metabolic/Laboratory - Other (HYPERCHLORIDEMIA)	1/42 (2.4%)	1	0/8 (0%)	0
Metabolic/Laboratory - Other (HYPERPHOSPHATEMIA)	1/42 (2.4%)	1	0/8 (0%)	0
Metabolic/Laboratory - Other (INCREASED CHLORIDE)	1/42 (2.4%)	1	0/8 (0%)	0
Metabolic/Laboratory - Other (INCREASED FIBRINOGEN)	0/42 (0%)	0	1/8 (12.5%)	1
Metabolic/Laboratory - Other (PRE-ALBUMIN)	1/42 (2.4%)	1	0/8 (0%)	0
Neutrophils/granulocytes (ANC/AGC)	39/42 (92.9%)	39	7/8 (87.5%)	7
PTT (Partial Thromboplastin Time)	8/42 (19%)	8	1/8 (12.5%)	1
Platelets	40/42 (95.2%)	40	7/8 (87.5%)	7
Weight gain	10/42 (23.8%)	10	0/8 (0%)	0
Weight loss	8/42 (19%)	8	0/8 (0%)	0
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	2/42 (4.8%)	2	0/8 (0%)	0
Albumin, serum-low (hypoalbuminemia)	38/42 (90.5%)	38	8/8 (100%)	8
Alkalosis (metabolic or respiratory)	1/42 (2.4%)	1	0/8 (0%)	0
Anorexia	25/42 (59.5%)	25	6/8 (75%)	6
Bicarbonate, serum-low	8/42 (19%)	8	1/8 (12.5%)	1
Calcium, serum-high (hypercalcemia)	8/42 (19%)	8	0/8 (0%)	0
Calcium, serum-low (hypocalcemia)	29/42 (69%)	29	6/8 (75%)	6
Dehydration	4/42 (9.5%)	4	0/8 (0%)	0
Glucose, serum-high (hyperglycemia)	30/42 (71.4%)	30	8/8 (100%)	8
Glucose, serum-low (hypoglycemia)	16/42 (38.1%)	16	1/8 (12.5%)	1
Magnesium, serum-high (hypermagnesemia)	12/42 (28.6%)	12	1/8 (12.5%)	1
Magnesium, serum-low (hypomagnesemia)	22/42 (52.4%)	22	6/8 (75%)	6
Phosphate, serum-low (hypophosphatemia)	26/42 (61.9%)	26	5/8 (62.5%)	5
Potassium, serum-high (hyperkalemia)	12/42 (28.6%)	12	2/8 (25%)	2
Potassium, serum-low (hypokalemia)	32/42 (76.2%)	32	7/8 (87.5%)	7
Sodium, serum-high (hypernatremia)	9/42 (21.4%)	9	3/8 (37.5%)	3
Sodium, serum-low (hyponatremia)	34/42 (81%)	34	8/8 (100%)	8
Triglyceride, serum-high (hypertriglyceridemia)	28/42 (66.7%)	28	6/8 (75%)	6
Uric acid, serum-high (hyperuricemia)	1/42 (2.4%)	1	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) (Extremity-lower)	1/42 (2.4%)	1	1/8 (12.5%)	1
Muscle weakness, generalized or specific area (not due to neuropathy) (Extremity-upper)	1/42 (2.4%)	1	0/8 (0%)	0
Musculoskeletal/Soft Tissue - Other (NOT SPECIFIED)	1/42 (2.4%)	1	0/8 (0%)	0
Musculoskeletal/Soft Tissue - Other (OCCASIONAL ACHES AND PAINS)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Back)	3/42 (7.1%)	3	0/8 (0%)	0
Pain (Bone)	2/42 (4.8%)	2	0/8 (0%)	0
Pain (Chest wall)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Extremity-limb)	9/42 (21.4%)	9	0/8 (0%)	0
Pain (Joint)	3/42 (7.1%)	3	0/8 (0%)	0
Pain (Neck)	3/42 (7.1%)	3	0/8 (0%)	0
Nervous system disorders
Neurology - Other (ACHY FEELING)	1/42 (2.4%)	1	0/8 (0%)	0
Neurology - Other (DYSTONIC REACTION)	1/42 (2.4%)	1	0/8 (0%)	0
Neurology - Other (GENERALIZED TENDERNESS)	1/42 (2.4%)	1	0/8 (0%)	0
Neuropathy: cranial (CN VII Motor-face; Sensory-taste)	1/42 (2.4%)	1	0/8 (0%)	0
Neuropathy: motor	1/42 (2.4%)	1	0/8 (0%)	0
Neuropathy: sensory	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Head/headache)	5/42 (11.9%)	5	0/8 (0%)	0
Somnolence/depressed level of consciousness	1/42 (2.4%)	1	0/8 (0%)	0
Syncope (fainting)	1/42 (2.4%)	1	0/8 (0%)	0
Taste alteration (dysgeusia)	4/42 (9.5%)	4	0/8 (0%)	0
Tremor	1/42 (2.4%)	1	0/8 (0%)	0
Psychiatric disorders
Confusion	2/42 (4.8%)	2	1/8 (12.5%)	1
Insomnia	3/42 (7.1%)	3	0/8 (0%)	0
Mood alteration (Agitation)	2/42 (4.8%)	2	0/8 (0%)	0
Mood alteration (Anxiety)	4/42 (9.5%)	4	1/8 (12.5%)	1
Mood alteration (Depression)	1/42 (2.4%)	1	0/8 (0%)	0
Psychosis (hallucinations/delusions)	2/42 (4.8%)	2	2/8 (25%)	2
Renal and urinary disorders
Bladder spasms	2/42 (4.8%)	2	0/8 (0%)	0
Cystitis	2/42 (4.8%)	2	0/8 (0%)	0
Hemoglobinuria	1/42 (2.4%)	1	1/8 (12.5%)	1
Hemorrhage, GU (Bladder)	2/42 (4.8%)	2	0/8 (0%)	0
Hemorrhage, GU (Urinary NOS)	2/42 (4.8%)	2	0/8 (0%)	0
Pain (Bladder)	1/42 (2.4%)	1	0/8 (0%)	0
Proteinuria	12/42 (28.6%)	12	0/8 (0%)	0
Renal/Genitourinary - Other (DECREASED URINE OUTPUT)	1/42 (2.4%)	1	0/8 (0%)	0
Renal/Genitourinary - Other (FLUID RETENTION)	2/42 (4.8%)	2	0/8 (0%)	0
Urinary retention (including neurogenic bladder)	3/42 (7.1%)	3	0/8 (0%)	0
Reproductive system and breast disorders
Pain (Pelvis)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Penis)	1/42 (2.4%)	1	1/8 (12.5%)	1
Pain (Scrotum)	2/42 (4.8%)	2	0/8 (0%)	0
Vaginal mucositis	0/42 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	3/42 (7.1%)	3	0/8 (0%)	0
Atelectasis	2/42 (4.8%)	2	0/8 (0%)	0
Bronchospasm, wheezing	1/42 (2.4%)	1	0/8 (0%)	0
Cough	13/42 (31%)	13	2/8 (25%)	2
Dyspnea (shortness of breath)	3/42 (7.1%)	3	0/8 (0%)	0
Hemorrhage, pulmonary/upper respiratory (Nose)	18/42 (42.9%)	18	0/8 (0%)	0
Hemorrhage, pulmonary/upper respiratory (Respiratory tract NOS)	1/42 (2.4%)	1	0/8 (0%)	0
Hypoxia	10/42 (23.8%)	10	1/8 (12.5%)	1
Mucositis/stomatitis (clinical exam) (Larynx)	1/42 (2.4%)	1	0/8 (0%)	0
Mucositis/stomatitis (clinical exam) (Pharynx)	3/42 (7.1%)	3	1/8 (12.5%)	1
Mucositis/stomatitis (functional/symptomatic) (Pharynx)	1/42 (2.4%)	1	1/8 (12.5%)	1
Nasal cavity/paranasal sinus reactions	0/42 (0%)	0	1/8 (12.5%)	1
Pain (Larynx)	1/42 (2.4%)	1	0/8 (0%)	0
Pain (Throat/pharynx/larynx)	8/42 (19%)	8	4/8 (50%)	4
Pleural effusion (non-malignant)	3/42 (7.1%)	3	0/8 (0%)	0
Pneumonitis/pulmonary infiltrates	2/42 (4.8%)	2	0/8 (0%)	0
Pulmonary/Upper Respiratory - Other (CONGESTION)	1/42 (2.4%)	1	0/8 (0%)	0
Pulmonary/Upper Respiratory - Other (HYPERCARBIA)	1/42 (2.4%)	1	0/8 (0%)	0
Pulmonary/Upper Respiratory - Other (RHINORRHEA)	1/42 (2.4%)	1	0/8 (0%)	0
Pulmonary/Upper Respiratory - Other (RUNNY NOSE)	1/42 (2.4%)	1	0/8 (0%)	0
Pulmonary/Upper Respiratory - Other (TACHYPNEIC)	2/42 (4.8%)	2	0/8 (0%)	0
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (DRY LIPS)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (FACIAL ABRAISIONS)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (INGROWN TOENAIL)	0/42 (0%)	0	1/8 (12.5%)	1
Dermatology/Skin - Other (LACERATION)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (PEELING SKIN)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (PERIORBITAL ECCHYMOSES)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (PSEUDOMEMBRANOUS CHANGES)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (SORE/SCAB)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (SUN BURN)	1/42 (2.4%)	1	0/8 (0%)	0
Dermatology/Skin - Other (ZOSTER LESION)	1/42 (2.4%)	1	0/8 (0%)	0
Dry skin	4/42 (9.5%)	4	0/8 (0%)	0
Hair loss/alopecia (scalp or body)	5/42 (11.9%)	5	0/8 (0%)	0
Hyperpigmentation	5/42 (11.9%)	5	0/8 (0%)	0
Hypopigmentation	1/42 (2.4%)	1	0/8 (0%)	0
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	3/42 (7.1%)	3	0/8 (0%)	0
Pruritus/itching	8/42 (19%)	8	3/8 (37.5%)	3
Rash/desquamation	19/42 (45.2%)	19	1/8 (12.5%)	1
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	1/42 (2.4%)	1	0/8 (0%)	0
Rash: hand-foot skin reaction	1/42 (2.4%)	1	0/8 (0%)	0
Skin breakdown/decubitus ulcer	1/42 (2.4%)	1	0/8 (0%)	0
Sweating (diaphoresis)	1/42 (2.4%)	1	0/8 (0%)	0
Ulceration	1/42 (2.4%)	1	0/8 (0%)	0
Vascular disorders
Flushing	3/42 (7.1%)	3	0/8 (0%)	0
Hematoma	1/42 (2.4%)	1	0/8 (0%)	0
Hemorrhage/Bleeding - Other (EPISTAXIS)	2/42 (4.8%)	2	0/8 (0%)	0
Hemorrhage/Bleeding - Other (EYE)	1/42 (2.4%)	1	0/8 (0%)	0
Hemorrhage/Bleeding - Other (HEMATURIA)	1/42 (2.4%)	1	1/8 (12.5%)	1
Hemorrhage/Bleeding - Other (HEMOPTYSIS)	1/42 (2.4%)	1	0/8 (0%)	0
Hemorrhage/Bleeding - Other (NOSE BLEED)	1/42 (2.4%)	1	0/8 (0%)	0
Hemorrhage/Bleeding - Other (TONGUE BLEED)	1/42 (2.4%)	1	0/8 (0%)	0
Hypertension	8/42 (19%)	8	0/8 (0%)	0
Hypotension	13/42 (31%)	13	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.