Table 2.
Phase I studies with trabectedin in combination
| First author | No Pts | Type of tumor | Drug | Range of trabectedin dose | MTD | DLTs | RD |
|---|---|---|---|---|---|---|---|
| Sessa (2009)46 | 49 | Solid tumors | Cisplatin 40 mg/m2, d1, 8 q21-d | 0.3–0.7 mg/m2 3-h infusion, q21-d |
• Cisplatin 40 mg/m2, d1, 8 q21-d + Trabectedin 0.7 mg/m2 | Neutropenia | Cisplatin (40 mg/m2) q21-d + Trabectedin 0.6 mg/m2 |
| Sessa (2013)47 | 47 | Solid tumors | Cisplatin 75 mg/m2, d1 q21-d | 0.75 mg/m2 3-h infusion, q21-d |
• Cisplatin (75 mg/m2) q21-d + Trabectedin 0.75 mg/m2 | Neutropenia | Cisplatin (75 mg/m2) q21-d + Trabectedin 0.60 mg/m2 |
| Vidal (2012)48 | 44 | Solid tumors (Carboplatin treated) | Carboplatin AUC4, q21-d |
0.5–1.2 mg/m2 3-h infusion, q21-d |
• Carboplatin AUC5 q21-d + Trabectedin 0.8 mg/m2 | Neutropenia | Carboplatin AUC4 q28-d* + Trabectedin 0.8 mg/m2 |
| Solid tumors (Carboplatin naïve) |
Carboplatin AUC5, q21-d |
• Not reached | – To be defined | ||||
| von Mehren (2008)50 | 36 | Solid tumors | PLD 30 mg/m2, q21-d | 0.4–1.3 mg/m2 3-h infusion, q21-d |
• PLD 30 mg/m2 q21-d + Trabectedin 1.1 mg/m2 | Neutropenia Hepatic |
nd |
| Chu (2010)53 | 27 | Solid tumors | TAX 80–120 mg/m2, q14-d | 0.525–0.775 mg/m2 3-h infusion, q14-d |
• TAX 120 mg/m2 + Trabectedin 0.65 mg/m2 | Neutropenia | TAX 120 mg/m2 + Trabectedin 0.65 mg/m2 |
| Messersmith (2008)54 | 15 | Solid tumors | GEM 800–1,000 mg/m2 d1, 8, 15, q28-d |
0.3–0.58 mg/m2 d1, 8, 15, q28-d | • Not reached | Not defined | GEM 1,000 mg/m2 d1, 8, 15 q28-d + Trabectedin 0.4 mg/m2 3-h infusion |
| Gore (2012)55 | 40 | Solid tumors | Capecitabine 2,000 or 1,600 mg/m2, orally d2–15, q21-d |
0.4–1.3 mg/m2 3-h infusion, q21-d |
• Capecitabine 2,000 mg/m2, orally d2–15 q21-d + Trabectedin 0.75 mg/m2 |
Gastrointestinal | Capecitabine 1,600 mg/m2, orally d2–15 q21-d + Trabectedin 1.1 mg/m2 |
Notes:
*
In the 4-week schedule, rescheduling was necessary due to frequent dose delays.
Abbreviations: d, day; DLT, dose-limiting toxicity; GEM, gemcitabine; h, hours; MTD, maximum tolerated dose; nd, not defined; No, number; PLD, pegylated liposomal doxorubicin; Pts, patients; q, every; RD, recommended dose; TAX, taxane; AUC, area under curve.