A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer

Leena Gandhi, Matthew W. Harding, Marcus Neubauer, Corey J. Langer, Melvin Moore, Helen J. Ross, Bruce E. Johnson, Thomas J. Lynch

Research output: Contribution to journalArticle

66 Scopus citations


BACKGROUND. Tumors with multidrug resistance (MDR) frequently up-regulate efflux proteins, including MDR-associated protein (MRP-1) and P-glycoprotein (Pgp). MDR represents an obstacle to successful chemotherapy treatment and is reversible in Pgp- or MRP-1-expressing cells by the inhibitor VX-710. A Phase II study was designed to evaluate VX-710 in combination with doxorubicin and vincristine in patients with sensitive, recurrent small cell lung cancer (SCLC). METHODS. Eligible patients had recurrent SCLC after a response to first-line chemotherapy. Stage 1 safety evaluation was completed with planned expansion if 9 responses were confirmed in the first 35 patients. Patients were treated every 21 days until progression or intolerable adverse events (AEs). RESULTS. Thirty-six patients were enrolled from 1998 to 2000. Neutropenia was the major toxicity, occurring in 26 of 36 patients (72%). Neutropenia was more severe (30% vs 20% grade 4) and developed earlier (58% vs 38% in Cycle 1) among the 15 patients who were enrolled prior to an amendment that required neutropenia prophylaxis. Four patients died on study: 2 from infections likely related to therapy and 2 from cancer progression. Seven of 36 patients (19%) had partial responses; 6 patients sustained responses through 6 cycles of treatment, with 1 response lasting 3 years. Three additional patients had unconfirmed responses, and 4 patients had stable disease. The median survival was 6 months. No correlative 99mTc-sestamibi uptake in tumor tissue was observed with the addition of VX-710 in this study. CONCLUSIONS. The addition of VX-710 to doxorubicin and vincristine therapy did not significantly enhance antitumor activity or survival. Although there were durable responses, criteria were not met to proceed with Stage 2 expansion.

Original languageEnglish (US)
Pages (from-to)924-932
Number of pages9
Issue number5
StatePublished - Mar 1 2007



  • Carcinoma
  • Clinical trials
  • Lung neoplasm
  • Multidrug resistance
  • Phase II
  • Small cell
  • VX-710

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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