Table 6. . Second-line drug combinations which have been explored in high-grade osteosarcoma.

Drug combination	Ref.
Vincristine + methotrexate + doxorubicin	[27]
Vincristine + high-dose methotrexate + cisplatin	[28]
Vinorelbine + cyclophosphamide	[29]
Paclitaxel (used as single drug)	[32]
Docetaxel + gemcitabine	[38,44,45]
Etoposide + high-dose methotrexate + ifosfamide	[47]
Etoposide + high-dose methotrexate + doxorubicin + cisplatin + ifosfamide	[50,51]
Etoposide + ifosfamide	[53]
Etoposide + cyclophosphamide	[75]
Etoposide + high-dose ifosfamide	[54]
Etoposide + carboplatin	[80]
Etoposide + ifosfamide + doxorubicin + methotrexate	[55]
Bleomycin + doxorubicin + cisplatin + methotrexate + dactinomycin + cyclophosphamide	[60–64]
Bleomycin (used as single drug) with electroporation	[65]
Carboplatin (used as single drug)	[78,79]
Carboplatin + ifosfamide + etoposide	[81]
Carboplatin + high-dose methotrexate + doxorubicin + ifosfamide	[82]
Carboplatin + doxorubicin + cyclophosphamide + etoposide	[83]
Topotecan (used as single drug)	[88,89]
Topotecan + cyclophosphamide	[90–92]
Topotecan + ifosfamide + carboplatin + etoposide, alternating with cisplatin and doxorubicin	[93]
Irinotecan (used as single drug)	[94,95]
Irinotecan + gemcitabine	[96]
Irinotecan + gefitinib (EGF inhibitor)	[97]
Irinotecan + temsirolimus (mTOR inhibitor) + temozolomide	[98]

Second-line drugs are in bold.