A phase I study of combination therapy of the oral fluorinated pyrimidine compound S-1 with low-dose cisplatin twice-a-week administration (JFMC27-9902 Step2) in patients with advanced gastric cancer using a continual reassessment method.

Abstract

OBJECTIVE:

We conducted a Phase I study to evaluate the safety and efficacy of a combination of S-1 with semi-weekly low-dose cisplatin in patients with unresectable/recurrent gastric cancer to determine the recommended dose (RD) for a subsequent Phase II study.

METHODS:

S-1 was administered orally at 80-120 mg/body/day based on body surface area. One cycle consisted of the consecutive administration of S-1 for 28 days followed by 14 days rest. Three dose levels, 7.5, 10, and 15 mg/m(2)/day, were set for cisplatin, which was administered twice-a-week for 4 weeks followed by 2 weeks of rest in each cycle. Dose-limiting toxicity (DLT) data were continually monitored to enable decisions regarding cisplatin dose escalation and deescalation based on a new dose-finding algorithm using a continual reassessment method (CRM). The CRM target toxicity level to estimate the RD was set at 20%.

RESULTS:

Eight and five patients were treated at cisplatin dose levels of 10 and 15 mg/m(2)/day, respectively. Two DLTs occurred at both dose levels. On the basis of this data, the CRM estimated the RD to be 10 mg/m(2)/day of cisplatin. Three patients of eight patients treated with 10 mg/m(2)/day of cisplatin exhibited a confirmed partial response during the treatment period.

CONCLUSION:

For future trials examining the safety and efficacy of daily S-1 with semi-weekly cisplatin in patients with unresectable/recurrent gastric cancer, we found a cisplatin RD of 10 mg/m(2)/day.

• Authors: Satoshi Morita, Bunzo Nakata, Akihito Tsuji, Yasushi Mitachi, Tetsuhiko Shirasaka, Shigetoyo Saji, Yasuo Ohashi, Junichi Sakamoto, Kosei Hirakawa
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 37 Issue 12 Pg. 924-9 (Dec 2007) ISSN: 1465-3621 [Electronic] England
• PMID: 18211983 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Cisplatin

Topics

• Administration, Oral
• Adult
• Aged
• Algorithms
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carcinoma (drug therapy, secondary)
• Cisplatin (administration & dosage, adverse effects)
• Drug Administration Schedule
• Drug Combinations
• Female
• Humans
• Injections, Intravenous
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Oxonic Acid (administration & dosage, adverse effects)
• Patient Selection
• Research Design
• Stomach Neoplasms (drug therapy, pathology)
• Tegafur (administration & dosage, adverse effects)
• Treatment Outcome