Phase II study of trabectedin in pretreated patients with advanced colorectal cancer.
OBJECTIVE
This open-label, nonrandomized, phase II study was aimed at evaluating the efficacy and toxicity of trabectedin over a 3-hour intravenous infusion every 3 weeks in patients with pretreated advanced colorectal cancer.


METHODS
Twenty-one patients were enrolled: 5 patients (23.8%) were treated with 1650 microg/m(2), 10 patients (47.6%) with 1300 microg/m(2), and 6 patients (28.6%) with 1100 microg/m(2). Response to treatment was assessed according to World Health Organization criteria, and toxicities were graded according to National Cancer Institute Common Toxicity Criteria, version 2.0.


RESULTS
The median number of treatment cycles per patient was 2 (range, 1-6 cycles). No objective responses were reported. Four patients (19%; 95% confidence interval [CI], 5.5%-41.9%) exhibited stable disease lasting for a median of 3.6 months (range, 2.4-4.9 months). The median time to progression was 1.5 months (95% CI, 1.3-1.6 months), and the median overall survival was 4.4 months (95% CI, 3-7.5 months; n=2 censored). The main grade 3/4 toxicities were transient asymptomatic transaminase increase (alanine aminotransferase, 66.7% of patients; aspartate aminotransferase, 57.1%) and neutropenia (42.8%). No toxic deaths were reported.


CONCLUSIONS
Trabectedin 1300 microg/m(2) given as a 3-hour intravenous infusion every 3 weeks was well tolerated but lacked activity in pretreated advanced-stage colorectal cancer. Therefore, further clinical trials with this trabectedin schedule as a single agent are not warranted.
Paz-Ares
Luis
L
Medical Oncology Deparment, Hospital Universitario 12 de Octubre, Madrid, Spain.
Rivera-Herreros
Fernando
F
Díaz-Rubio
Eduardo
E
García
Margarita
M
Casado
Esther
E
Cubedo
Ricardo
R
Gravalos
Cristina
C
Alfaro
Vicente
V
Gómez
Javier
J
Izquierdo
Miguel Angel
MA
Tabernero
Josep
J
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004149:Dioxoles / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D013997:Time Factors; D000077606:Trabectedin
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin