Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy.

Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues.
We conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m(2) days 1 through 14 then 300 mg/m(2) days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A.
Forty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n = 23; arm B, n = 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] = 0.38; 95% CI, 0.20 to 0.72; P = .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR = 0.51; 95% CI, 0.28 to 0.94; P = .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P = .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR = 0.92; 95% CI, 0.47 to 1.78; P = .80).
Radioembolization with (90)Y-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC.
AuthorsAlain Hendlisz, Marc Van den Eynde, Marc Peeters, Geert Maleux, Bieke Lambert, Jaarke Vannoote, Katrien De Keukeleire, Chris Verslype, Luc Defreyne, Eric Van Cutsem, Philippe Delatte, Thierry Delaunoit, Nicola Personeni, Marianne Paesmans, Jean-Luc Van Laethem, Patrick Flamen
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 23 Pg. 3687-94 (Aug 10 2010) ISSN: 1527-7755 [Electronic] United States
PMID20567019 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Yttrium Radioisotopes
  • Fluorouracil
  • Adenocarcinoma (secondary, therapy)
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating (administration & dosage)
  • Colorectal Neoplasms (pathology, therapy)
  • Embolization, Therapeutic
  • Female
  • Fluorouracil (administration & dosage)
  • Humans
  • Infusions, Intravenous
  • Injections, Intra-Arterial
  • Liver Neoplasms (secondary, therapy)
  • Male
  • Microspheres
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Yttrium Radioisotopes (administration & dosage)

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