New developments in treatment of ovarian carcinoma: focus on trabectedin

Figures & data

Table 1 Summary of efficacy of trabectedin as a single agent in relapsed ovarian cancer

Study	PFI (months)	n	CR	PR	ORR	Median PFS (months)
Sessa et al^Citation20	<6 months	30	0	2 (7%)	7%	NR
	≥6 months	29	1 (3%)	9 (31%)	34%	NR
Krasner et al^Citation21	<6 months	81	0	5 (6%)	6%	2.0
	6–12 months	43	1 (2%)	9 (22%)	24%	4.0
	≥12 months	23	3 (13%)	5 (22%)	35%	5.1
Del Campo et al^Citation22	<6 months	7	0	1	14.3%	NR
	6–12 months	48	NR	NR	29.9%	5.6
	≥12 months	52	NR	NR	48.1%	10.8

Abbreviations: PFI, platinum-free interval; CR, complete response; PR, partial responses; ORR, overall response rate; NR, not reported.

Table 2 Summary of the most commonly encountered Grade 3–4 side effects in single-agent trials of trabectedin in patients with ovarian cancer

Study	Schedule	Infusion time (hours)	n	AST	ALT	Bilirubin	Neutropenia	Thrombocytopenia	Fatigue	Nausea vomiting
Sessa et al^Citation20	1650 μg/m^2/3 wks	3	6	6 (100%)a	−	0	NA	NA	NA	NA
	1500 μg/m^2/3 wks	3	12	10 (84%)a	−	0	NA	NA	NA	NA
	1300 μg/m^2/3 wks	3	41	31 (75%)a	−	0	17 (41%)	3 (7%)	3 (7%)	2 (5%)
Krasner et al^Citation21	580 μg/m^2/wk 3/4 wks	3	147	4 (3%)	18 (12%)	0	12 (8%)	4 (3%)	8 (5%)	8 (5%)
Del Campo et al^Citation22	1500 μg/m^2/3 wks	24	54	19 (35%)	30 (56%)	0	29 (54%)	4 (8%)	8 (15%)	2 (4%)
	1300 μg/m^2/3 wks	3	53	10 (19%)	31 (58%)	1 (2%)	20 (38%)	5 (10%)	4 (8%)	3 (6%)

Note:

a Pooled data for AST/ALT elevation.

Abbreviations: AST, aspartate transaminase; ALT, alanine transaminase; wk, week.

Table 3 Summary of data on trabectedin-based combination of potential interest in ovarian cancer

Combination	Reference	Schedule	Recommended Phase II dose	Dose-limiting toxicity	Efficacy in ovarian cancer patients	Comments
Trabectedin	^Citation27	Days 1 and 8 every 21 days	500–600 μg/m^2	Prolonged neutropenia	Four of 13 patients (31%) with OC had a PR	Deceiving efficacy-wise and toxic
Cisplatin		Days 1 and 8 every 21 days	40 mg/m^2
Trabectedin	^Citation29	Days 1, 8 and 15 every 28 days	400 μg/m^2	None	NR
Gemcitabine		Days 1, 8 and 15 every 28 days	1000 mg/m^2
Trabectedin	^Citation28	Day 1 every 21 days	1100 μg/m^2	Grade 3–4 transaminitis lasting > 7 days	One patient with PPC had a PR and 2 of 4 patients with OC has SD	A subsequent phase III trial in patients with ROC showed improved RR and PFS compared with PLD alone
PLD		Day 1 every 21 days	30 mg/m^2
Trabectedin	^Citation30	Day 1 every 21 days	1100 μg/m^2	Grade 4 neutropenia and/or febrile neutropenia before primary prophylaxis with filgrastim. Grade 3 fatigue.	NR	A subsequent phase II trial in patients with ROC showed a RR, PFS and OS of 30%, 4.4 months and 12.5 months respectively
Docetaxel		Day 1 every 21 days	60 mg/m^2
Trabectedin	^Citation31	Day 2 every 14 days	650 μg/m^2	Grade 4 neutropenia lasting 5 days or more, dose delays beyond 8 days	One patient with OC has PD (no response)
Paclitaxel		Day 1 every 14 days	120 mg/m^2

Abbreviations: PLD, pegylated liposomal doxorubicin; OC, ovarian cancer; ROC, relapsed ovarian cancer; PR, partial response; NR, not reported; RR, response rate; PFS, progression-free survival; OS, overall survival; PD, progressive disease; SD, stable disease.

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