Yamazaki K.,Shizuoka Cancer Center |
Kuwano H.,Gunma University |
Ojima H.,Gunma Prefectural Cancer Center Ota |
Otsuji T.,Dongo Hospital |
And 10 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015
Purpose: Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) enhances antitumor activity. LV is thus often added to 5-FU-based regimens for the treatment of metastatic colorectal cancer (mCRC). A combination of S-1, oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a previous phase I trial. We therefore conducted a randomized phase II trial to evaluate efficacy and safety of SOL compared with mFOLFOX6. Methods: Patients with mCRC and no prior chemotherapy were randomly assigned to receive either SOL or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1 week and oxaliplatin (85 mg/m2) on day 1, repeated every 2 weeks. Results: Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median progression-free survival was 9.6 months in the SOL group and 6.9 months in the mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40]. The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 % CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and diarrhea (11 vs 3.9 %). Conclusions: SOL demonstrated promising efficacy and acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL combined with molecular target agents are warranted. © 2015 Springer-Verlag Berlin Heidelberg.
Munemoto Y.,Fukuiken Saiseikai Hospital |
Kanda M.,Nagoya University |
Ishibashi K.,Saitama University |
Hata T.,Osaka University |
And 11 more authors.
BMC Cancer | Year: 2015
Background: Although number of elderly patients with metastatic colorectal cancer (mCRC) is rapidly increasing, this population is often underrepresented in clinical trials. Recently, a phase II trial demonstrated that capecitabine and oxaliplatin (XELOX) combined with bevacizumab XELOX plus bevacizumab was effective and well tolerated by elderly patients with mCRC who reside in Western countries. The aim of this study was to evaluate the safety and efficacy of XELOX plus bevacizumab for Japanese patients aged ≤75years with mCRC. Methods: This prospective, open-label phase II trial recruited patients aged ≤75years with previously untreated mCRC between March 2010 and January 2012. Treatment consisted of 7.5mg/kg of intravenous bevacizumab and 130mg/m2 of oxaliplatin on day 1 of each cycle combined with 2000mg/m2 of oral capecitabine per day on days 1-14 of each cycle. Treatment was repeated every 3weeks until disease progression or termination of the study. The primary endpoint was progression-free survival; the secondary endpoints were toxicity, overall response rate, time-to-treatment failure, and overall survival. Results: Thirty-six patients (male 58%; median age 78years; colon cancer 67%) met all eligibility criteria and received at least one course of the planned treatment. The median time-to-treatment failure was 7.0months. Twelve patients (33.3%) experienced adverse effects (AEs)≤grade 3 and frequent AEs≤grade 3, including neutropenia (22.2%) and neuropathy (13.9%). Hypertension was the most frequent AE≤grade 3 associated with bevacizumab (11.1%). Low baseline creatinine clearance associated significantly with the incidence of AEs≤grade 3. Response and disease control rates were 55.6 and 91.7%, respectively. Median progression-free and overall survival times were 11.7months (95% confidence interval, 8.0-13.4months) and 22.9months, respectively. Conclusion: XELOX combined with bevacizumab was well tolerated by selected Japanese patients aged ≤75years with mCRC patients, and controlled clinical trials are now required to determine the survival benefit. © 2015 Munemoto et al.
Imamura H.,Toyonaka Municipal Hospital |
Kishimoto T.,Sakai Municipal Hospital |
Takiuchi H.,Osaka Medical College |
Kimura Y.,Sakai Municipal Hospital |
And 8 more authors.
Journal of Chemotherapy | Year: 2014
Background: S-1zcisplatin (CDDP) is the standard treatment for advanced gastric cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based chemotherapy for elderly patients is unclear. Therefore, we conducted a multicenter phase II study of S-1 monotherapy for AGC in elderly patients. Materials and Methods: Chemotherapy-naïve patients aged over 75 years with AGC were enrolled. The starting dose of S-1 was determined on the basis of body surface area and modified according to the creatinine clearance value. S-1 was administered twice a day during a 4-week period followed by a 2-week rest period. Results: Thirty-five patients were enrolled. The response rate (RR) was 14.3% and the median overall survival was 14.6 months. Grade 3 or more severe adverse events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue (6%). There were no treatment-related deaths. Conclusion: Our study indicates that S-1 monotherapy is safe and well tolerated in chemotherapy-naïve elderly patients with AGC, but exerts limited activity when given using a tailor-made dosing strategy based on renal function. © 2014 Edizioni Scientifiche per l'Informazione su Farmaci e Terapia.
Kimura Y.,Nippon Telegraph and Telephone |
Yano H.,Hyogo Prefectural Nishinomiya Hospital |
Imamura H.,Sakai Municipal Hospital |
Fujitani K.,National Hospital Organization Osaka National Hospital |
And 8 more authors.
Japanese Journal of Clinical Oncology | Year: 2013
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. © The Author 2012. Published by Oxford University Press. All rights reserved.
Oba K.,Hokkaido University |
Matsuoka M.,Dongo Hospital |
Satoh T.,Kinki University |
Muro K.,Aichi Cancer Center Hospital |
And 3 more authors.
Japanese Journal of Clinical Oncology | Year: 2011
We are conducting an open-label multicentre phase II study to evaluate the efficacy and safety of the combination therapy of XELOX and bevacizumab in late-stage elderly patients with unresectable advanced/recurrent colorectal cancer. The primary endpoint of the study is progression-free survival. The secondary endpoints are the toxicity, overall response rate, time to treatment failure and overall survival. Thirty-five patients are required for the study. © The Author (2010). Published by Oxford University Press. All rights reserved.