A phase I study of combination chemotherapy with gemcitabine and oral UFT for advanced non-small cell lung cancer

Seto, Takashi; Yoh, K.; Asoh, Hiroshi; Yamamoto, Hidehiko; Semba, Hiroshi; Ichinose, Yukito

doi:10.1038/sj.bjc.6600337

Cited by 11 publications

(11 citation statements)

References 16 publications

(14 reference statements)

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“…The overall response rate of the present trial using UFT and gemcitabine was 41%. In a phase I trial of this combination chemotherapy, the response rate of patients without prior chemotherapy was also reported to be 45% (Seto et al, 2002). This high antitumour effect may lend support to the sequence of administration of UFT and gemcitabine.…”

Section: Discussionmentioning

confidence: 86%

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UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial

et al. 2005

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A multi-institutional phase II trial was conducted to evaluate the efficacy and toxicity of combination chemotherapy consisting of gemcitabine and UFT, which is composed of tegafur and uracil, for non-small-cell lung cancer (NSCLC) patients. Patients with advanced NSCLC received an oral administration of UFT (tegafur 200 mg m À2 ) b.i.d. from days 1 to 14 and intravenous injection of gemcitabine 900 mg m À2 on days 8 and 15. This treatment was repeated every 4 weeks. A total of 44 patients were enrolled into this trial. The median age of all patients was 74 years, with 23 patients younger than 75 years and 21 patients with 75 years of age or older. A total of 18 patients (41%) achieved a partial response. The median survival time was 13.2 months and the 1-year survival rate was 59%. The most common grade 3 -4 toxicity was neutropenia (57%). The frequency of grade 3 nonhaematologic toxicities was less than 5%. In addition, no significant difference in the response, survival or toxicities was observed between the patients younger than and those older than 75 years of age. This combination chemotherapy demonstrated a promising effectiveness and acceptable toxicity in patients with advanced NSCLC, even in patients older than 75 years.

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Section: Discussionmentioning

confidence: 86%

“…In our prior phase I trial, the combination chemotherapy of UFT plus gemcitabine was found to be feasible (Seto et al, 2002). The most appropriate schedule and dosing was 200 mg m À2 of UFT b.i.d for 14 consecutive days with 900 mg m À2 gemcitabine on days 8 and 15.…”

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confidence: 99%

UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial

et al. 2005

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“…These results suggested that administration of UFT in combination with gemcitabine had at least some activity against advanced pancreatic cancer. Although the response rate of non-small cell lung cancer patients to UFT as a single agent was reported to be only 6-8%, a combination chemotherapy of UFT and gemcitabine demonstrated a 33% response rate and an extremely low incidence of adverse events in a phase I study [16] . While both UFT and gemcitabine inhibit DNA synthesis, UFT inhibits thymidylate synthase and gemcitabine causes DNA chain termination.…”

Section: Discussionmentioning

confidence: 99%

“…Major treatmentrelated adverse events other than hematologic toxicity were gastrointestinal symptoms such as anorexia and nausea. In a Japanese phase I study with advanced nonsmall cell lung cancer patients, a 3-weekly combination therapy of oral UFT 400 mg/m 2 per day for 14 days and gemcitabine 900 mg/m 2 on days 8 and 15 was shown to be well tolerated [16] . In the present trial, at the recommended oral UFT and gemcitabine doses of 400 mg per day for 14 days and 1,000 mg/m 2 , respectively, 3 patients received two cycles or more of chemotherapy without dose reduction or delay.…”

Section: Discussionmentioning

confidence: 99%

A Phase I Study of Oral Uracil-Tegafur Prior to Weekly Intravenous Gemcitabine in Patients with Advanced Pancreatic Cancer

Tanno

Nakano²,

Osanai³

et al. 2006

Chemotherapy

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Background: Gemcitabine is widely accepted as the first-line agent for advanced pancreatic cancer. The antitumor cell activity of gemcitabine is higher when administered after 5-fluorouracil (5-FU) rather than before 5-FU in an in vitro study. The present study was conducted to define the maximum tolerated dose and dose-limiting toxicity associated with an oral fluoropyrimidine prodrug that combines uracil and tegafur (UFT), given prior to weekly intravenous gemcitabine in patients with advanced pancreatic cancer. Methods: Over a 21-day cycle, gemcitabine was given intravenously over 30 min on days 8 and 15, while UFT was given orally from days 1 to 14. The dose of UFT used was 400 mg per day, given as two doses. The dose of gemcitabine was escalated in a stepwise fashion from 800 (level 1, n = 3) to 900 mg/m² (level 2, n = 6) and then to 1,000 mg/m² (level 3, n = 3), such that totally 12 patients received the combination chemotherapy. Results: During the first cycle, grade 3 leukopenia was observed in 2 patients at dose level 1. Only 1 patient treated at dose level 2 experienced dose-limiting toxicity (grade 3 elevated transaminase), including additional patients treated at this dose level. No grade 3/4 toxicities occurred in patients treated at dose level 3. A significant response was observed in 1 out of 12 patients (8.3%). Seven patients (58.3%) had stable disease, while 4 patients (33.3%) showed disease progression. Conclusions: The combination chemotherapy of oral UFT and gemcitabine was convenient, well tolerated and may benefit patients with advanced pancreatic cancer. Doses recommended for further study of this schedule are gemcitabine 1,000 mg/m² and UFT 400 mg/day.

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“…The efficacy of gemcitabine combined with 5-FU has been relatively well established based on several phase I and II trials which reported that the combination therapy is superior to gemcitabine or 5-FU alone [14, 15, 16, 17]. In a Japanese phase I study, the combination therapy with gemcitabine and oral UFT was shown to be tolerable in advanced non-small cell lung cancer patients [22]. The efficacy and low toxicity of the regimen were also shown in advanced colorectal carcinoma and pancreatic cancer patients in Spanish phase II trials [23, 24].…”

Section: Discussionmentioning

confidence: 99%

Phase II Study of Gemcitabine Combined with Uracil-Tegafur in Metastatic Pancreatic Cancer

Lee

Park²,

Kim³

et al. 2004

Oncology

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Objective: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. Methods: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m² once weekly for 3 consecutive weeks, and oral UFT 390 mg/m²/day (in 3 divided doses) on days 1–14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. Results: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1–6 cycles). The median age was 52 years (range 28–69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8–45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9–13.6). The median overall survival was 5.8 months (range 0.5–13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2–73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3–4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). Conclusion: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen.

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A phase I study of combination chemotherapy with gemcitabine and oral UFT for advanced non-small cell lung cancer

Cited by 11 publications

References 16 publications

UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial

UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial

A Phase I Study of Oral Uracil-Tegafur Prior to Weekly Intravenous Gemcitabine in Patients with Advanced Pancreatic Cancer

Phase II Study of Gemcitabine Combined with Uracil-Tegafur in Metastatic Pancreatic Cancer

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