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

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.

• Authors: Ken Kato, Keisho Chin, Takaki Yoshikawa, Kensei Yamaguchi, Yasushi Tsuji, Taito Esaki, Kenji Sakai, Masami Kimura, Tetsuya Hamaguchi, Yasuhiro Shimada, Yasuhiro Matsumura, Ryuji Ikeda
• Journal: Investigational new drugs (Invest New Drugs) Vol. 30 Issue 4 Pg. 1621-7 (Aug 2012) ISSN: 1573-0646 [Electronic] United States
• PMID: 21728023 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Micelles
• NK105
• Paclitaxel

Topics

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