Management of Ewing sarcoma family of tumors: Current scenario and unmet need

Table 1 Randomized studies of chemotherapy in upfront treatment of Ewing sarcoma family tumors

Study	Patients (n)	Intervention1	Outcome	P	Comments
IESS I[78]	Localized (342)	(1) VAC	5-yr RFS 24%		Beneficial of doxorubicin and benefit of lung RT
		(2) VACD	60%	--
		(3) VAC + Lung RT	44%
IESS II[29]	Non-pelvic, localized (214)	VACD	5-yr RFS	0.04	Intermittent, high dose better
		(1) Intermittent, high dose (3 weekly)	73%
		(2) Continuous, moderate dose (weekly)	56%
POG-CCSG INT-0091[6]	Localized (398)	(1) VDC	5-yr RFS 54%	0.005	IE is beneficial in addition to VDC in localized but not in metastatic disease
		(2) VDC + IE	69%
	Metastatic (120)	(1) VDC	22%	NS
		(2) VDC + IE	22%
POG-CCSG	Localized (478)		5-yr EFS	NS	Dose intensification not effective
INT-154[32]		(1) VDC + IE (standard)	70%
		(2) VDC + IE (intensified)	72%
COG AEWS0031[33]	Localized (568)	(1) VDC + IE (3 weekly)	5-yr EFS 65%	0.05	3-weekly better than 2-weekly with no increase in toxicity
		(2) VDC + IE (2 weekly)	73%
EICESS92[7]	n = 155	SR (localized and < 100 mL) 4#VAIA → 8# VAIA vs 8#VACD	3-yr EFS 73% vs 74%	NS	Cyclophosphamide and ifosfamide is similar in efficacy in SR patients
	n = 492	HR (metastatic, > 100 mL)	47% vs 52%	0.12	No benefit of etoposide in HR patients
		14# VAIA vs 14#EVAIA
Euro-Ewing 99[49]	Detailed in Table 2

¹All chemotherapy regimens mentioned in the table is used in neoadjuvant setting followed-by local therapy (in terms of surgery and/or radiotherapy) followed by further adjuvant chemotherapy. EFS: Event free survival; EVAIA: Etoposide, vincristine, dactinomycin, ifosfamide, doxorubicin; HR: High risk; IE: Ifosfamide, etoposide; NS: Not significant; RFS: Relapse free survival; RT: Radiotherapy; SR: Standard risk; VAC: Vincristine, dactinomycin, cyclophosphamide; VACD: Vincristine, dactinomycin, cyclophosphamide, doxorubicin; VAIA: Vincristine, dactinomycin, ifosfamide, doxorubicin; VDC: Vincristine, doxorubicin, cyclophosphamide.