Phase II study of NK105, a paclitaxel-incorporating micellar nanoparticle, for previously treated advanced or recurrent gastric cancer

Invest New Drugs. 2012 Aug;30(4):1621-7. doi: 10.1007/s10637-011-9709-2. Epub 2011 Jul 5.

Abstract

Purpose: NK105 is a new drug delivery system formulation for paclitaxel (PTX) whose recommended dose (RD) is 150 mg PTX equivalent/m(2) administered every 3 weeks, as determined in a phase I trial. This study aimed to evaluate the efficacy and safety of NK105 in patients with advanced gastric cancer after failure of first-line chemotherapy.

Experimental design: Eligible patients had measurable disease and one chemotherapeutic regimen except taxane. NK105 (150 mg PTX equivalent/m(2)) was administered by a 30-minute intravenous infusion every 3 weeks without anti-allergic premedication until disease progression, unacceptable toxicity or patient refusal. The primary efficacy endpoint was best overall response rate (ORR) post baseline. The secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS). All adverse events were reported using CTCAE v3.0.

Results: Between November 2007 and July 2009, 57 patients were enrolled and 56 were evaluable for efficacy. Two complete responses and 12 partial responses were observed for an ORR of 25%. The median PFS was 3.0 months, the median TTF was 2.8 months, and the median OS was 14.4 months. Drug related toxicity was mainly mild (grades 1-2) to severe (grades 3-4); other data: neutropenia (64.9%); leukopenia (17.5%); lymphopenia (8.8%); neuropathy-sensory (1.8%); fatigue (3.5%); and stomatitis (1.8%). There were no treatment-related deaths.

Conclusions: This study of NK105 (150 mg PTX equivalent/m(2)) proves the concept for the modest activity and tolerability of a new drug delivery system formulation for PTX. A phase III trial will be evaluated to clarify survival benefit.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Demography
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Micelles*
  • Middle Aged
  • Nanoparticles / chemistry*
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Paclitaxel / adverse effects
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / therapeutic use*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology*
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Micelles
  • NK105
  • Paclitaxel