Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma Journal Article


Authors: Laverdiere, C.; Kolb, E. A.; Supko, J. G.; Gorlick, R.; Meyers, P. A.; Maki, R. G.; Wexler, L.; Demetri, G. D.; Healey, J. H.; Huvos, A. G.; Goorin, A. M.; Bagatell, R.; Ruiz-Casado, A.; Guzman, C.; Jimeno, J.; Harmon, D.
Article Title: Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma
Abstract: BACKGROUND. Recurrent osteosarcoma is a drug-resistant disease with a dismal prognosis. The objective of this Phase II study was to evaluate the activity of ecteinascidin 743 (ET-743) as a salvage therapy in these patients. METHODS. Patients with recurrent osteosarcoma who had received standard chemotherapeutic agents were eligible. ET-743 was administered at a dose of 1500 μg/m2 as a 24-hour infusion every 3 weeks. Pharmacokinetic studies were performed during the first cycle. RESULTS. Twenty-five patients were enrolled, 23 of whom were assessable for response (median age of 18 years; range, 12-67 years). The median number of previous chemotherapeutic agents was five (range, three to eight previous agents). Sixty-one cycles were administered (median number of cycles per patient was 2; range, 1-9 cycles per patient). Three patients (12%) achieved minor responses (49% 36% and 25%, respectively). Fifteen patients (60%) developed a transient elevation of hepatic transaminases (Grade 3 or 4 [according to the National Cancer Institute Common Toxicity Criteria]), which was not cumulative. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 12 patients (48%) and 6 patients (24%), respectively. The mean area under the curve (AUC) in 4 patients experiencing Grade 4 toxicity (76.4 ± 29.3 ng × hr/mL) was significantly greater (P = 0.034) than that in those for whom the most severe toxicity was Grade 3 (39.5 ± 17.2 ng × hr/mL [n = 12]) or Grade 1-2 (52.6 ± 15.6 ng × hr/mL [n = 5]). There were no other significant correlations found between pharmacokinetic variables and patient characteristics, toxicity, or therapeutic response. CONCLUSIONS. ET-743 was found to be well tolerated in heavily pretreated osteosarcoma patients but had limited antitumor activity as a single agent. The combination of ET-743 with cisplatin or doxorubicin should be considered. © 2003 American Cancer Society.
Keywords: osteosarcoma; adolescent; adult; child; clinical article; controlled study; school child; aged; bone neoplasms; middle aged; clinical trial; constipation; drug activity; drug tolerability; neutropenia; salvage therapy; cisplatin; doxorubicin; area under the curve; dose response; liver dysfunction; skin manifestation; methotrexate; recurrent cancer; anorexia; controlled clinical trial; nephrotoxicity; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; antineoplastic activity; continuous infusion; ifosfamide; asthenia; flushing; sarcoma; correlation analysis; drug response; antineoplastic agents, alkylating; drug infusion; bleomycin; tamoxifen; open study; octreotide; phase 1 clinical trial; trabectedin; dioxoles; isoquinolines; tetrahydroisoquinolines; phase ii study; humans; human; male; female; priority journal; article; ecteinascidin-743 (et-743)
Journal Title: Cancer
Volume: 98
Issue: 4
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2003-08-15
Start Page: 832
End Page: 840
Language: English
DOI: 10.1002/cncr.11563
PUBMED: 12910529
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Richard G Gorlick
    120 Gorlick
  2. Leonard H Wexler
    132 Wexler
  3. Robert Maki
    211 Maki
  4. Paul Meyers
    247 Meyers
  5. John H Healey
    381 Healey
  6. Anders E Kolb
    16 Kolb
  7. Andrew G Huvos
    209 Huvos