Prospects and challenges of novel natural marine-derived compounds in melanoma treatment

Table 1 Completed clinical trials of marine-derived compounds in melanoma treatment

Compound name	Source organism	NCT number and Ref.	Phase	Patient population	Methods	Total/melanoma	Clinical efficacy	Most frequent grade 3+ treatment-related adverse events
Eribulin	Marine sponge (Halichondria okadai)	I	Advanced solid tumors (including melanoma)	Monotherapy	40/2	-	Neutropenia: 9/38 (24%); fatigue: 4/38 (11%); peripheral neuropathy: 3/38 (8%)
Plitidepsin (Aplidin®)	Marine tunicate (Aplidium albicans)	II	Advanced malignant melanoma	Monotherapy	39/39	PR/CR: 2/35 (5.7%); SD: 5/35 (14.3%); median OS: 3.5 months	Myalgia: 3/35 (8.6%); injection site reaction: 2/35 (5.7%); hypersensitivity: 1/35 (2.9%); hypotension: 1/35 (2.9%)
		I-II	Advanced malignant melanoma	Combination (with dacarbazine)	I: 28/28, II: 38/38	I: PR/CR: 3/19 (15.8%); SD: 4/19 (21%); II: PR/CR: 6/28 (21.4%); SD: 9/28 (32.1%)	ALT elevation: 10/36 (28%); fatigue; nausea/vomiting; hypersensitivity; creatine phosphokinase elevation
Kahalalide F	Marine mollusk (Elysia rufescens)	II	Advanced malignant melanoma	Monotherapy	24/24	PR/CR: 0/24 (0%); SD: 5/21 (24%); median OS: 10.8 months	Transaminase elevation (AST/ALT): 14/24 (58%); gamma-glutamyl transferase: 2/24 (8%); lymphopenia: 2/24 (8%)
		I	Advanced solid tumors (including melanoma)	Monotherapy	38/5	PR/CR: 1/5 (20%)	Transaminase elevation (AST/ALT); hypokalemia; hypoglycemia
Salinosporamide A (Marizomib)	Marine actinomycete (Salinispora tropica)	NCT00667082, Millward et al[90]	I	Advanced solid tumors (including melanoma)	Combination (with vorinostat)	22/17	PR/CR: 0/17 (0%); SD: 11/17 (64.7%)	Fatigue: 4/22 (18%); nausea: 5/22 (23%); vomiting: 4/22 (18%); diarrhea: 2/22 (9%); deep vein thrombosis: 3/22 (14%); thrombocytopenia (grade 4): 1/22 (5%)
Didemnin B	Marine tunicate (Trididemnum solidum)	II	Metastatic melanoma	Monotherapy	14/14	PR/CR: 0/14 (0%)	Hypersensitivity reactions; nausea, vomiting, diarrhea
		II	Advanced malignant melanoma	Monotherapy	19/19	PR: 1/19 (5.3%); SD: 7/19 (36.8%)	Anaphylactoid reactions: 7/19 (37%); severe myopathy: 1/19 (5%)
Bryostatin 1	Marine bryozoan (Bugula neritina)	NCT00006022	Ia/Ib	Metastatic melanoma	Monotherapy	17/-
		NCT00112476, Plimack et al[89]	I	Advanced or metastatic solid tumors (including melanoma)	Combination (with temsirolimus)	30/-	PR: 3/25 (12%); SD: 13/25 (52%);	Neutropenia (10%); thrombosis (10%); creatinine elevation
		II	Metastatic melanoma	Monotherapy	34/34	SD: 7/34 (21%)	Myalgia: 6/34 (18%); lethargy
		II	Metastatic melanoma	Monotherapy	16/16	SD: 1/15 (6.7%); median survival: 134 days	Myalgia: 6/16 (37.5%); nausea/vomiting: 1/16 (6.25%)
		I	Advanced solid tumors (including melanoma)	Monotherapy	19/-		Myalgia: 3/3 (100%) at highest dose (65 µg/m²); cellulitis/phlebitis
		I	Advanced malignancies (including melanoma)	Monotherapy	35/2	PR/CR: 2/2 (100%)	Myalgia: 4/11 (36%); headache: 5/11 (45%); phlebitis: 11/23 (48%); acute infusion reactions (dyspnea, flushing, hypotension, bradycardia): 6/35 (17%)
		II	Metastatic melanoma	Monotherapy	49/49	PR/CR: 1/49 (2%)	Myalgia: > 90%; nausea/vomiting: 6/49 (12%)
		II	Metastatic melanoma	Monotherapy	18/18	SD: 1/18 (5.6%)	Myalgia: 1/18 (5.6%)
Dolastatin-10	Marine mollusk (Dolabella auricularia)	II	Metastatic melanoma	Monotherapy	12/12	Objective response rate: 0/12 (0%)	Neutropenia: 4/12 (33%)
Trabectedin (Yondelis®)	Marine tunicate a (Ecteinascidia turbinat)	I	Advanced solid tumors (including melanoma)	Monotherapy	72/2	PR/CR: 1/2 (50%)	Neutropenia: 15/72 (20%); elevated transaminases: 40/103 cycles (39%); fatigue: 14/72 (19%)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CR: Complete response; OS: Overall survival; PR: Partial response; SD: Stable disease.