Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma (EURAMOS-1)

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ClinicalTrials.gov Identifier: NCT00134030

Recruitment Status : Completed

First Posted : August 24, 2005

Results First Posted : June 7, 2023

Last Update Posted : June 7, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

National Cancer Institute (NCI)

University College, London

Medical Research Council

Information provided by (Responsible Party):

Babasola (Sola) Popoola, University College, London

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Localized Osteosarcoma Metastatic Osteosarcoma
Interventions	Drug: Cisplatin Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Ifosfamide Drug: Methotrexate Biological: Peginterferon Alfa-2b Other: Quality-of-Life Assessment Other: Questionnaire Administration Procedure: Therapeutic Conventional Surgery
Enrollment	1334

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	MAP-GR	MAPifn	MAP-PR	MAPIE
Arm/Group Description	Patients receive doxorubicin IV con...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin IV con...
Arm/Group Description	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Peginterferon Alfa-2b: Given subcutaneously Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery
Period Title: Overall Study
Started	359	357	310	308
Completed	359	357	310	308
Not Completed	0	0	0	0

Baseline Characteristics

Arm/Group Title		MAP-GR	MAPifn	MAP-PR	MAPIE	Total
Arm/Group Description		Patients receive doxorubicin IV con...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin IV con...	Total of all reporting groups
Arm/Group Description		Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Peginterferon Alfa-2b: Given subcutaneously Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Total of all reporting groups
Overall Number of Baseline Participants		359	357	310	308	1334
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
		14 (11 to 16)	14 (12 to 16)	15 (11 to 18)	15 (12 to 17)	14 (12 to 17)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
	Female	148 41.2%	147 41.2%	136 43.9%	117 38.0%	548 41.1%
	Male	211 58.8%	210 58.8%	174 56.1%	191 62.0%	786 58.9%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
New Zealand		1	2	2	0	5
Canada		20	9	7	11	47
United States		128	134	142	139	543
Australia		2	3	3	5	13
Switzerland		8	3	7	7	25
Austria		2	5	5	8	20
Belgium		14	14	9	7	44
Czechia		3	0	2	1	6
Denmark		2	6	2	2	12
Finland		0	0	1	2	3
Germany		85	90	60	63	298
Hungary		5	6	5	3	19
Ireland		0	0	0	1	1
Netherlands		21	18	16	10	65
Norway		7	10	12	5	34
Sweden		14	10	4	5	33
United Kingdom		47	47	33	39	166
Site of tumour Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
	Femur	179 49.9%	191 53.5%	154 49.7%	166 53.9%	690 51.7%
	Tibia	113 31.5%	102 28.6%	75 24.2%	76 24.7%	366 27.4%
	Fibula	14 3.9%	20 5.6%	17 5.5%	13 4.2%	64 4.8%
	Humerus	36 10.0%	33 9.2%	39 12.6%	27 8.8%	135 10.1%
	Radius	5 1.4%	5 1.4%	4 1.3%	6 1.9%	20 1.5%
	Ulna	2 0.6%	0 0.0%	2 0.6%	1 0.3%	5 0.4%
	Scapula/clavicle	2 0.6%	1 0.3%	3 1.0%	2 0.6%	8 0.6%
	Pelvis/sacrum	5 1.4%	5 1.4%	8 2.6%	11 3.6%	29 2.2%
	Rib	3 0.8%	0 0.0%	3 1.0%	3 1.0%	9 0.7%
	Other	0 0.0%	0 0.0%	5 1.6%	3 1.0%	8 0.6%
Location of tumour on the bone Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
	Proximal	156 43.5%	150 42.0%	114 36.8%	109 35.4%	529 39.7%
	Diapysis	13 3.6%	12 3.4%	11 3.5%	12 3.9%	48 3.6%
	Distal	180 50.1%	189 52.9%	166 53.5%	168 54.5%	703 52.7%
	N/A (not long bone)	10 2.8%	6 1.7%	19 6.1%	19 6.2%	54 4.0%
Pathological fracture at diagnosis Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
	No	321 89.4%	308 86.3%	276 89.0%	270 87.7%	1175 88.1%
	Yes	37 10.3%	49 13.7%	34 11.0%	35 11.4%	155 11.6%
	Data missing	1 0.3%	0 0.0%	0 0.0%	3 1.0%	4 0.3%
Lung metastases Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
	No/possible	324 90.3%	321 89.9%	272 87.7%	280 90.9%	1197 89.7%
	Yes	35 9.7%	36 10.1%	38 12.3%	28 9.1%	137 10.3%
Histological classification Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	359 participants	357 participants	310 participants	308 participants	1334 participants
	Conventional	320 89.1%	322 90.2%	288 92.9%	289 93.8%	1219 91.4%
	Telangiectatic	25 7.0%	20 5.6%	11 3.5%	6 1.9%	62 4.6%
	Small cell	2 0.6%	1 0.3%	3 1.0%	2 0.6%	8 0.6%
	High-grade surface	3 0.8%	5 1.4%	5 1.6%	6 1.9%	19 1.4%
	Other	4 1.1%	2 0.6%	0 0.0%	1 0.3%	7 0.5%
	Data missing	5 1.4%	7 2.0%	3 1.0%	4 1.3%	19 1.4%

Outcome Measures

1.Primary Outcome


Title	Event-free Survival (EFS)
Description	EFS is defined as time from randomisation to the first of: death, dete...
Description	EFS is defined as time from randomisation to the first of: death, detection of local recurrence or metastasis, progression of metastatic disease, or detection of a secondary malignancy. EFS will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Follow up per participant will be assessed for up to 10 years. The 3 year EFS is provided as a summary.
Time Frame	From date of randomization to date of the event.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	MAP-GR	MAPifn	MAP-PR	MAPIE
Arm/Group Description:	Patients receive doxorubicin IV con...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin IV con...
Arm/Group Description:	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Peginterferon Alfa-2b: Given subcutaneously Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery
Overall Number of Participants Analyzed	359	357	310	308
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage EFS
	74 (69 to 79)	77 (72 to 81)	55 (49 to 60)	53 (47 to 59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MAP-GR, MAPifn
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.214
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.61 to 1.12
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MAP-PR, MAPIE
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.86
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.78 to 1.23
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MAP-PR, MAPIE
	Comments	Secondary RMST analysis performed in poor response group, due to evidence of non-proportional hazards.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.69
	Comments	[Not Specified]
	Method	Difference in RMST
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95% -3.3 to 4.9
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Percentage of Patients With Overall Survival
Description	Overall survival is time from randomization until death from any cause...
Description	Overall survival is time from randomization until death from any cause. Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals. Participants will be assessed for up to 10 years. 5 year overall survival is provided as a summary.
Time Frame	From date of randomization to date of death.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	MAP-GR	MAPifn	MAP-PR	MAPIE
Arm/Group Description:	Patients receive doxorubicin IV con...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin IV con...
Arm/Group Description:	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Peginterferon Alfa-2b: Given subcutaneously Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery
Overall Number of Participants Analyzed	359	357	310	308
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	84 (80 to 88)	84 (81 to 88)	68 (63 to 73)	68 (63 to 73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MAP-GR, MAPifn
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.804
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95% 0.69 to 1.33
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MAP-PR, MAPIE
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.674
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95% 0.81 to 1.39
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Toxicity as Measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Description	Percentages of patients experiencing grade 3 and 4 adverse events. The...
Description	Percentages of patients experiencing grade 3 and 4 adverse events. These will be compared using chi-square tests or Fisher's exact tests where appropriate.
Time Frame	Adverse events are assessed for up to 10 years per participant.

Outcome Measure Data

Analysis Population Description

Adverse events are only analyzed in participants who started treatment and for whom toxicity data were provided.


Arm/Group Title	MAP-GR	MAPifn	MAP-PR	MAPIE
Arm/Group Description:	Patients receive doxorubicin IV con...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin, cispl...	Patients receive doxorubicin IV con...
Arm/Group Description:	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Peginterferon Alfa-2b: Given subcutaneously Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery
Overall Number of Participants Analyzed	356	355	301	298
Measure Type: Count of Participants Unit of Measure: Participants
	348 97.8%	340 95.8%	287 95.3%	281 94.3%

Adverse Events

Time Frame	From randomisation until 30 days after last protocol treatment up to 10 years.
Adverse Event Reporting Description	The total number of participants represented in the Serious Adverse Events Table is 1,334 (MAP-GR +MAPifn +MAP-PR+MAPIE). On an intention to treat basis, this includes16 patients (across all arms) who did not start treatment or had no adverse event data available.

Arm/Group Title	MAP-GR		MAPifn		MAP-PR		MAPIE
Arm/Group Description	Patients receive doxorubicin IV con...		Patients receive doxorubicin, cispl...		Patients receive doxorubicin, cispl...		Patients receive doxorubicin IV con...
Arm/Group Description	Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20, 21, 24, 25, 28, and 29. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery		Patients receive doxorubicin, cisplatin, and high-dose MTX as in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in weeks 30-104. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Peginterferon Alfa-2b: Given subcutaneously Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery		Patients receive doxorubicin, cisplatin, and high-dose MTX as in group 1 arm I. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery		Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. Cisplatin: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Ifosfamide: Given IV Methotrexate: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies Therapeutic Conventional Surgery: Undergo amputation or limb salvage surgery
All-Cause Mortality
	MAP-GR		MAPifn		MAP-PR		MAPIE
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events Serious Adverse Events
	MAP-GR		MAPifn		MAP-PR		MAPIE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/359 (13.65%)		76/357 (21.29%)		36/310 (11.61%)		43/308 (13.96%)
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA ^* 1	7/359 (1.95%)	11	5/357 (1.40%)	6	3/310 (0.97%)	4	10/308 (3.25%)	17
NEUTROPENIA ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
THROMBOCYTOPENIA ^* 1	1/359 (0.28%)	1	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
Cardiac disorders
ACUTE LEFT VENTRICULAR FAILURE ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
ATRIAL THROMBOSIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
CARDIAC ARREST ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
CARDIAC FAILURE ^* 1	0/359 (0.00%)	0	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
CARDIOMYOPATHY ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
CARDIOVASCULAR INSUFFICIENCY ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
CONGESTIVE CARDIOMYOPATHY ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
LEFT VENTRICULAR DYSFUNCTION ^* 1	1/359 (0.28%)	1	2/357 (0.56%)	2	1/310 (0.32%)	1	2/308 (0.65%)	2
LEFT VENTRICULAR FAILURE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
PERICARDIAL EFFUSION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
TACHYCARDIA ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
VENTRICULAR DYSFUNCTION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
MYOCARDITIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
VENTRICULAR FIBRILLATION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Ear and labyrinth disorders
DEAFNESS BILATERAL ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	1/310 (0.32%)	1	0/308 (0.00%)	0
Endocrine disorders
AUTOIMMUNE THYROIDITIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
BASEDOW'S DISEASE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
THYROIDITIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Eye disorders
OPTIC NEUROPATHY ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Gastrointestinal disorders
ABDOMINAL PAIN ^* 1	1/359 (0.28%)	1	2/357 (0.56%)	2	0/310 (0.00%)	0	1/308 (0.32%)	1
ANAL FISTULA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
ANAL ULCER ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
NAUSEA ^* 1	1/359 (0.28%)	2	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
PANCREATITIS ACUTE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
STOMATITIS ^* 1	3/359 (0.84%)	3	1/357 (0.28%)	1	0/310 (0.00%)	0	1/308 (0.32%)	1
VOMITING ^* 1	3/359 (0.84%)	3	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
COLITIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	2/310 (0.65%)	2	0/308 (0.00%)	0
CONSTIPATION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
MOUTH ULCERATION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
RECTAL HAEMORRHAGE ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
General disorders
CHILLS ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
COMPLICATION ASSOCIATED WITH DEVICE ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
IMPAIRED HEALING ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
INFUSION SITE THROMBOSIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
MUCOSAL INFLAMMATION ^* 1	3/359 (0.84%)	3	2/357 (0.56%)	2	6/310 (1.94%)	7	3/308 (0.97%)	3
PYREXIA ^* 1	4/359 (1.11%)	7	3/357 (0.84%)	5	2/310 (0.65%)	2	2/308 (0.65%)	2
INFUSION SITE ERYTHEMA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Hepatobiliary disorders
HEPATOTOXICITY ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
LIVER DISORDER ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
VENOOCCLUSIVE LIVER DISEASE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
Immune system disorders
ANAPHYLACTIC REACTION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
HYPERSENSITIVITY ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
Infections and infestations
ANAL ABSCESS ^* 1	0/359 (0.00%)	0	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
APPENDICITIS ^* 1	1/359 (0.28%)	1	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
ARTHRITIS BACTERIAL ^* 1	0/359 (0.00%)	0	2/357 (0.56%)	2	0/310 (0.00%)	0	1/308 (0.32%)	1
BACTERIAL SEPSIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
BRONCHOPULMONARY ASPERGILLOSIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	1/308 (0.32%)	1
CATHETER SITE INFECTION ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
CLOSTRIDIUM DIFFICILE COLITIS ^* 1	2/359 (0.56%)	2	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
CLOSTRIDIUM DIFFICILE INFECTION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
DEVICE RELATED INFECTION ^* 1	3/359 (0.84%)	3	6/357 (1.68%)	7	3/310 (0.97%)	3	1/308 (0.32%)	1
DEVICE RELATED SEPSIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
ECTHYMA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
ERYSIPELAS ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
ESCHERICHIA SEPSIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
FEBRILE INFECTION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
GASTROENTERITIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
H1N1 INFLUENZA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
HERPES ZOSTER ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
IMPLANT SITE CELLULITIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
INCISION SITE ABSCESS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
NEUTROPENIC INFECTION ^* 1	0/359 (0.00%)	0	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
NEUTROPENIC SEPSIS ^* 1	0/359 (0.00%)	0	2/357 (0.56%)	3	2/310 (0.65%)	2	1/308 (0.32%)	1
PERITONITIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
PNEUMONIA ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
RASH PUSTULAR ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
SEPSIS ^* 1	2/359 (0.56%)	2	1/357 (0.28%)	1	1/310 (0.32%)	1	4/308 (1.30%)	4
SEPTIC SHOCK ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
STAPHYLOCOCCAL INFECTION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
STAPHYLOCOCCAL SCALDED SKIN SYNDROME ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
STAPHYLOCOCCAL SEPSIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
STAPHYLOCOCCAL SKIN INFECTION ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
VASCULAR DEVICE INFECTION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
WOUND INFECTION ^* 1	1/359 (0.28%)	1	3/357 (0.84%)	3	0/310 (0.00%)	0	1/308 (0.32%)	1
WOUND INFECTION STAPHYLOCOCCAL ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
ABSCESS LIMB ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
HERPES SIMPLEX ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
POSTOPERATIVE WOUND INFECTION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	2/310 (0.65%)	2	0/308 (0.00%)	0
PSEUDOMONAL SEPSIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
SEPTIC ARTHRITIS STAPHYLOCOCCAL ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
VARICELLA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
FEMUR FRACTURE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
PERIPROSTHETIC FRACTURE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
POSTOPERATIVE WOUND COMPLICATION ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
RADIUS FRACTURE ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
TIBIA FRACTURE ^* 1	2/359 (0.56%)	2	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
TOXICITY TO VARIOUS AGENTS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
UPPER LIMB FRACTURE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
BLOOD CREATININE INCREASED ^* 1	1/359 (0.28%)	1	1/357 (0.28%)	1	0/310 (0.00%)	0	1/308 (0.32%)	1
CHEMOTHERAPEUTIC DRUG LEVEL INCREASED ^* 1	2/359 (0.56%)	2	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
DRUG CLEARANCE DECREASED ^* 1	2/359 (0.56%)	2	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
INFLUENZA B VIRUS TEST POSITIVE ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
PLATELET COUNT DECREASED ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	1/308 (0.32%)	1
TRANSAMINASES INCREASED ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
WHITE BLOOD CELL COUNT DECREASED ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	3
NEUTROPHIL COUNT DECREASED ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Metabolism and nutrition disorders
DEHYDRATION ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
Musculoskeletal and connective tissue disorders
BONE PAIN ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
JOINT SWELLING ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
OSTEOPOROTIC FRACTURE ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
PATHOLOGICAL FRACTURE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
BONE INFARCTION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	2/308 (0.65%)	2
EWING'S SARCOMA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
PAPILLARY THYROID CANCER ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
RENAL CELL CARCINOMA STAGE I ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
MYELODYSPLASTIC SYNDROME ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Nervous system disorders
ANOSMIA ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
CEREBRAL ARTERY EMBOLISM ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
DISTURBANCE IN ATTENTION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
ENCEPHALOPATHY ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	1/310 (0.32%)	1	0/308 (0.00%)	0
GENERALISED TONIC-CLONIC SEIZURE ^* 1	2/359 (0.56%)	2	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
HEMIPARESIS ^* 1	1/359 (0.28%)	1	2/357 (0.56%)	2	1/310 (0.32%)	1	0/308 (0.00%)	0
HEMIPLEGIA ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
LEUKOENCEPHALOPATHY ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
SEIZURE ^* 1	1/359 (0.28%)	1	1/357 (0.28%)	1	1/310 (0.32%)	2	0/308 (0.00%)	0
STUPOR ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
TOXIC ENCEPHALOPATHY ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
CYTOTOXIC OEDEMA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
DYSTONIA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
MONOPARESIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
PRESYNCOPE ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Product Issues
DEVICE DISLOCATION ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
DEVICE FAILURE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
THROMBOSIS IN DEVICE ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
Psychiatric disorders
ABNORMAL BEHAVIOUR ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
DEPRESSED MOOD ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
MANIA ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
SUICIDE ATTEMPT ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
Renal and urinary disorders
NEPHROPATHY TOXIC ^* 1	1/359 (0.28%)	1	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
RENAL FAILURE ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
RENAL IMPAIRMENT ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
ACUTE KIDNEY INJURY ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	2/310 (0.65%)	2	0/308 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
DYSPNOEA ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	1/310 (0.32%)	1	0/308 (0.00%)	0
EPISTAXIS ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
PLEURAL EFFUSION ^* 1	0/359 (0.00%)	0	2/357 (0.56%)	2	0/310 (0.00%)	0	0/308 (0.00%)	0
PULMONARY EMBOLISM ^* 1	1/359 (0.28%)	1	2/357 (0.56%)	2	1/310 (0.32%)	1	0/308 (0.00%)	0
HYPERSENSITIVITY PNEUMONITIS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
PLEURISY ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Skin and subcutaneous tissue disorders
RASH ERYTHEMATOUS ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
URTICARIA ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	1/310 (0.32%)	1	0/308 (0.00%)	0
Vascular disorders
DEEP VEIN THROMBOSIS ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
HYPOTENSION ^* 1	0/359 (0.00%)	0	0/357 (0.00%)	0	0/310 (0.00%)	0	1/308 (0.32%)	1
JUGULAR VEIN THROMBOSIS ^* 1	0/359 (0.00%)	0	1/357 (0.28%)	1	0/310 (0.00%)	0	0/308 (0.00%)	0
PELVIC VENOUS THROMBOSIS ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
PERIPHERAL ARTERY DISSECTION ^* 1	1/359 (0.28%)	1	0/357 (0.00%)	0	0/310 (0.00%)	0	0/308 (0.00%)	0
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA 22.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MAP-GR		MAPifn		MAP-PR		MAPIE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/359 (0.00%)		0/357 (0.00%)		0/310 (0.00%)		0/308 (0.00%)

Limitations and Caveats

In the good response patients (randomised to MAP-GR or MAPifn), 128 of 357 MAPifn patients completed the planned protocol treatment. Among poor response patients (randomised to MAP-PR or MAPie), 42% of registered patients were not randomised. Further patients were registered to the trial and joined a treatment cohort for follow-up but declined to join the randomisation or were not eligible. The data for these non-randomised patients are not presented here.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Prof Matt Sydes
Organization:	MRC Clinical Trials Unit at UCL
EMail:	mrcctu.euramos@ucl.ac.uk

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hazewinkel AD, Lancia C, Anninga J, van de Sande M, Whelan J, Gelderblom H, Fiocco M. Disease progression in osteosarcoma: a multistate model for the EURAMOS-1 (European and American Osteosarcoma Study) randomised clinical trial. BMJ Open. 2022 Mar 4;12(3):e053083. doi: 10.1136/bmjopen-2021-053083.

Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

Marina NM, Smeland S, Bielack SS, Bernstein M, Jovic G, Krailo MD, Hook JM, Arndt C, van den Berg H, Brennan B, Brichard B, Brown KLB, Butterfass-Bahloul T, Calaminus G, Daldrup-Link HE, Eriksson M, Gebhardt MC, Gelderblom H, Gerss J, Goldsby R, Goorin A, Gorlick R, Grier HE, Hale JP, Hall KS, Hardes J, Hawkins DS, Helmke K, Hogendoorn PCW, Isakoff MS, Janeway KA, Jurgens H, Kager L, Kuhne T, Lau CC, Leavey PJ, Lessnick SL, Mascarenhas L, Meyers PA, Mottl H, Nathrath M, Papai Z, Randall RL, Reichardt P, Renard M, Safwat AA, Schwartz CL, Stevens MCG, Strauss SJ, Teot L, Werner M, Sydes MR, Whelan JS. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. Lancet Oncol. 2016 Oct;17(10):1396-1408. doi: 10.1016/S1470-2045(16)30214-5. Epub 2016 Aug 25.

Whelan JS, Bielack SS, Marina N, Smeland S, Jovic G, Hook JM, Krailo M, Anninga J, Butterfass-Bahloul T, Bohling T, Calaminus G, Capra M, Deffenbaugh C, Dhooge C, Eriksson M, Flanagan AM, Gelderblom H, Goorin A, Gorlick R, Gosheger G, Grimer RJ, Hall KS, Helmke K, Hogendoorn PC, Jundt G, Kager L, Kuehne T, Lau CC, Letson GD, Meyer J, Meyers PA, Morris C, Mottl H, Nadel H, Nagarajan R, Randall RL, Schomberg P, Schwarz R, Teot LA, Sydes MR, Bernstein M; EURAMOS collaborators. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Ann Oncol. 2015 Feb;26(2):407-14. doi: 10.1093/annonc/mdu526. Epub 2014 Nov 24.

Layout table for additonal information

Responsible Party:	Babasola (Sola) Popoola, University College, London
ClinicalTrials.gov Identifier:	NCT00134030
Other Study ID Numbers:	AOST0331/ EURAMOS-1 NCI-2009-01066 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ISRCTN67613327 ( Registry Identifier: ISRCTN ) MRC-BO08 ( Other Identifier: MRC CTU ) MRC-EURAMOS1 ( Other Identifier: MRC CTU ) 06-93 ( Other Identifier: Children's Oncology Group ) CDR0000438714 ( Other Identifier: TBC ) COG-AOST0331 ( Other Identifier: Children's Oncology Group ) EU-20530 ( Other Identifier: TBC ) 2004-000242-20 ( EudraCT Number ) AOST0331 ( Other Identifier: Children's Oncology Group ) AOST0331 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted:	August 22, 2005
First Posted:	August 24, 2005
Results First Submitted:	November 21, 2022
Results First Posted:	June 7, 2023
Last Update Posted:	June 7, 2023

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