A phase I study of S-1 in combination with nab-paclitaxel in patients with unresectable or recurrent gastric cancer.

Abstract

BACKGROUND:

In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study.

METHODS:

The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m2 twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m2 on day 1 or 8.

RESULTS:

Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 220 mg/m2 on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 260 mg/m2 on day 1). The most common grade 3-4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab-paclitaxel or S-1 alone.

CONCLUSIONS:

Based on the present results, the RD was determined as level 3a (S-1 80 mg/m2 twice daily plus nab-paclitaxel 260 mg/m2 on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer.

• Authors: Norisuke Nakayama, Kenji Ishido, Keisho Chin, Ken Nishimura, Mizutomo Azuma, Satoshi Matsusaka, Yasuhiro Inokuchi, Satoshi Tanabe, Yosuke Kumekawa, Wasaburo Koizumi
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 20 Issue 2 Pg. 350-357 (Mar 2017) ISSN: 1436-3305 [Electronic] Japan
• PMID: 27189323 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Drug Combinations
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Paclitaxel

Topics

• Aged
• Albumins (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Drug Combinations
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms (drug therapy, secondary)
• Lung Neoplasms (drug therapy, secondary)
• Lymphatic Metastasis
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Neoplasm Staging
• Oxonic Acid (administration & dosage)
• Paclitaxel (administration & dosage)
• Peritoneal Neoplasms (drug therapy, secondary)
• Prognosis
• Stomach Neoplasms (drug therapy, pathology)
• Survival Rate
• Tegafur (administration & dosage)