A phase I study of triplet combination chemotherapy of paclitaxel, cisplatin and S-1 in patients with advanced gastric cancer.

Abstract

OBJECTIVE:

S-1 and cisplatin combination therapy is a standard regimen for patients with advanced gastric cancer in Japan. The primary objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of a triplet regimen adding paclitaxel to S-1 and cisplatin combination therapy.

METHODS:

Patients with previously untreated metastatic or recurrent gastric cancer were enrolled. Patients received S-1 (40 mg/m(2) p.o., twice daily, on days 1-21 every 35 days), cisplatin (30 mg/m(2) divided, on days 1 and 15) and paclitaxel (divided on days 1 and 15). The starting dose of paclitaxel was 50 mg/m(2) (level 1); the dose was escalated to 60 (level 2), 70 (level 3) and 80 mg/m(2) (level 4) in a stepwise fashion. Dose-limiting toxicity was determined during the first treatment cycle.

RESULTS:

Eighteen patients enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, one of the six patients had dose-limiting toxicity (one patient had grade 4 neutropenia) and at dose level 4, one of the six patients had dose-limiting toxicity (one patient had febrile neutropenia, hypoalbuminemia and fatigue of grade 3). The maximum tolerated dose was not reached at level 4; however, grade 3 hyponatremia and hypokalemia in two of the six patients occurred during the second treatment course at level 4. From the point of view of safety in the outpatient setting, the recommended dose of paclitaxel was determined at 70 mg/m(2). The overall response rate was 50%.

CONCLUSIONS:

The recommended dose of paclitaxel added to S-1 (80 mg/m(2) days 1-21) plus cisplatin (30 mg/m(2) days 1 and 15) was 70 mg/m(2) on days 1 and 15 of a 5-week cycle.

• Authors: Yutaka Kimura, Hiroshi Yano, Hiroshi Imamura, Kazumasa Fujitani, Motohiro Imano, Yukihiko Tokunaga, Masaki Matsuoka, Yukinori Kurokawa, Toshio Shimokawa, Hiroya Takiuchi, Toshimasa Tsujinaka, Hiroshi Furukawa
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 43 Issue 2 Pg. 125-31 (Feb 2013) ISSN: 1465-3621 [Electronic] England
• PMID: 23225911 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Drug Combinations
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Paclitaxel
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cisplatin (administration & dosage, adverse effects)
• Drug Administration Schedule
• Drug Combinations
• Fatigue (chemically induced)
• Female
• Humans
• Hypoalbuminemia (chemically induced)
• Hypokalemia (chemically induced)
• Hyponatremia (chemically induced)
• Male
• Middle Aged
• Neoplasm Staging
• Neutropenia (chemically induced)
• Oxonic Acid (administration & dosage, adverse effects)
• Paclitaxel (administration & dosage, adverse effects)
• Stomach Neoplasms (drug therapy, pathology)
• Tegafur (administration & dosage, adverse effects)
• Treatment Outcome