A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in women with advanced ovarian cancer refractory to paclitaxel therapy

Gynecol Oncol. 2002 Sep;86(3):302-10. doi: 10.1006/gyno.2002.6762.


Purpose: Incel (biricodar, VX-710) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug-resistance-associated protein (MRP1) expressing cells. This phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with advanced ovarian cancer refractory to prior paclitaxel therapy.

Experimental design: Eligible patients had paclitaxel-refractory disease defined as progressive disease after a minimum of two cycles of paclitaxel (weekly or 3-week schedule) or relapsed disease within 4 months of prior paclitaxel therapy. Patients received 80 mg/m(2) paclitaxel over 3 h starting 4 h after initiation of a 24-h continuous intravenous infusion of 120 mg/m(2)/h VX-710. Cycles were repeated every 3 weeks.

Results: Fifty patients received treatment and 45 were evaluable for response. VX-710 + paclitaxel therapy was generally well tolerated. Myelosuppression was the principal toxicity, with a median Cycle 1 nadir absolute neutrophil count of 0.27 x 10(9) cells/L and a 47% overall incidence of Grade 4 neutropenia. Mild to moderate peripheral neuritis or neuropathy was the primary nonhematologic toxicity, affecting 62% of patients. Other nonhematologic toxicities were generally mild to moderate and reversible. Paclitaxel area under the concentration-versus-time curve (AUC) (16 +/- 5.3 microg x h/mL) during the first treatment cycle was comparable to standard 175 mg/m(2) paclitaxel administered over 3 h. Of the 3 patients who achieved partial responses, 2 had progressed during prior paclitaxel therapy. Twelve patients maintained stable disease and 14/45 (31%) of patients had CA-125 reductions of 50-90% for up to 24 weeks. The median time-to-disease progression was 10 weeks for the intent-to-treat population and 20.7 weeks for the CA-125 responders.

Conclusions: The results suggest that VX-710 with paclitaxel has modest activity in paclitaxel-resistant ovarian cancer. Further research is warranted in less heavily treated patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors
  • Neoplasm Recurrence, Local / drug therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Piperidines / pharmacokinetics
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Multidrug Resistance-Associated Proteins
  • Piperidines
  • Pyridines
  • biricodar
  • Paclitaxel