Phase II study of paclitaxel, cisplatin, and 5-FU combination chemotherapy in patients with advanced gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15052-15052
Author(s):  
S. Cho ◽  
H. Shim ◽  
S. Lee ◽  
J. Ahn ◽  
D. Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Objective Response ◽  
Dose Intensity ◽  
Bone Marrow Suppression ◽  
Grade 3

15052 Background: Taxane has been used widely in advanced gastric cancer, but toxicities are problematic. To avoid the bone marrow suppression, docetaxel could be replaced paclitaxel to reduce bone marrow suppression and to improve the efficacy, we planned to augmentation of the dose intensity. This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Methods: Patients with histologically confirmed gastric adenocarcinoma, ECOG PS = 2, at least one measurable lesion and adequate organ functions were eligible. Paclitaxel (175 mg/m2) and cisplatin (75 mg/m2) were given as a 1-h intravenous infusion on day 1, followed by 5-FU (750 mg/m2) as a 24-h continuous infusion for 5 days. This cycle was repeated every 3 weeks. Results: Forty-five eligible patients (median age 56 years) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 20 (48.8%), a complete response in two, and a partial response in 18 patients. The median time to progression was 6.9 months (95% CI, 5.86–7.94), and the median overall survival was 13.1 months (95% CI, 8.83–17.37). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in 67 cycles (25%). Febrile neutropenia developed in three patients (7.3%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but grade 3 or 4 toxicity was not seen. Conclusions: The combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer. No significant financial relationships to disclose.

Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 162-162
Author(s):  
Sung Rok Kim ◽  
Sung-En Park ◽  
Young Jin Yuh ◽  
Byeong Seok Sohn ◽  
Hye Ran Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

162 Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m2/day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m2 and 100mg/m2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m2 and 100mg/m2, respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.

A phase II study of irinotecan, oxaliplatin, 5-fluorouracil, leucovorin (FOLFOXIRI) as a first-line chemotherapy in metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4076-4076
Author(s):  
J. Lee ◽  
W. Kang ◽  
S. Lee ◽  
J. Kwon ◽  
H. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Gastric Cancer ◽  
Efficacy And Safety ◽  
First Line ◽  
Grade 3

4076 Background: Previous phase II study showed a high efficacy and safety of FOLFOXIRI (irinotecan, oxaliplatin, 5-fluorouracil, leucovorin) combination chemotherapy in metastatic colorectal cancer. This non-randomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Methods: Patients with: histologically proven, bidimensionally measurable, metastatic gastric adenocarcinoma, age 18 - 70 years, with a performance status 0 - 2, no prior chemotherapy or at least 12 months after adjuvant therapy, life expectancy > 3 months, signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, repeated every 2 weeks until unacceptable toxicity, patients’ refusal, or up to 12 cycles. The planned sample size was 48 and the primary endpoint was response rate. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24 - 69) and male:female ratio was 1.3:1. In total, 379 cycles were administered with a median of 9 cycles per patient (range, 1–12) and 45/48 patients were evaluable for treatment response. Three patients were not assessable for response due patients’ refusal for further chemotherapy following the first cycle. By per-protocol analysis, the objective response rate was 73.3 % (95% CI, 60.8–85.8) with 2 CRs and 31 PRs. Four patients (9%) had stable disease and 8 patients (18%) had progressive disease. The estimated median survival of all patients was 14.0 months (95% CI, 11.8 - 16.2 ) and the estimated median time-to-progression was 8.9 months (95% CI, 6.7–11.0). In total of 379 cycles administered, most common grade 3/4 toxicities were neutropenia (11% of all cycles) and emesis (12%). Grade 2 peripheral neuropathy occurred in 5 patients. One (2%) patient had severe tumor bleeding and 5 (10%) patients experienced grade 3 diarrhea. Conclusions: FOLFOXIRI combination chemotherapy showed a very promising preliminary anti-tumor activity and was generally well tolerated as a first-line treatment for patients with metastatic gastric cancer. No significant financial relationships to disclose.

Multi-institutional phase II study of carboplatin-gemcitabine combination chemotherapy in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18179-18179
Author(s):  
J. Sasaki ◽  
H. Uramoto ◽  
K. Kashiwabara ◽  
H. Kishi ◽  
E. Moriyam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Group Performance ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Efficacy And Safety ◽  
Grade 3

18179 Background: Because elderly pts may tolerate platinum-based combination chemotherapy poorly, single-agent chemotherapy is selected for the treatment regimen. However, retrospective subgroup analyses have consistently indicated that elderly pts indeed benefit from platinum-based combination chemotherapy as well as their younger counterparts. This phase II study evaluated the efficacy and safety of carboplatin-gemcitabine combination chemotherapy in elderly pts with advanced NSCLC. Methods: Fifty-four pts aged more than 70 years old (median, 77; range, 70–88) with previously untreated advanced NSCLC were enrolled on this trial. Additional criteria included the presence of measurable lesions, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Pts received carboplatin at an area under the curve of 4 mg/ml/min on the first day and gemcitabine at 1000 mg/m2 on the first and eighth day of consecutive 3 week periods. The primary endpoint was to determine the objective response rate of this platinum-doublet regimen. The RECIST criteria were used to measure response. Results: Enrolled pts included 15/39 with stage IIIB/IV diseases. Fifty-one out of enrolled pts were eligible for efficacy and safety analyses. The median number of treatment cycles was 4 (range, 1–7). Fifteen partial responses (response rate: 29%) were obtained. The median TTP was 118 days. Hematological toxicities of grade 3/4 included leukopenia (46%), neutropenia (72%) and thrombocytopenia (50%). Non-hematological toxicities of grade 3/4 included nausea (6%), appetite loss (7%), fatigue (7%) and infection (9%). Conclusions: The combination carboplatin-gemcitabine at these doses has shown activity with a favorable toxicity profile for fit elderly pts with advanced NSCLC. No significant financial relationships to disclose.

Pharmacogenetics of peripheral neuropathy in elderly patients (>65 years) with advanced gastric cancer receiving oxaliplatin-based chemotherapy within a randomized phase II study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14515-e14515
Author(s):  
E. Goekkurt ◽  
S. Al-Batran ◽  
L. Obermann ◽  
C. Pauligk ◽  
N. Homann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Neuropathy ◽  
Elderly Patients ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Cox Regression ◽  
Phase Ii Study ◽  
High Grade ◽  
Significant Difference ◽  
Grade 3

e14515 Background: Peripheral neuropathy (PNP) is a dose-limiting side effect of oxaliplatin based chemotherapy. High grade PNP may compromise quality of life especially in elderly patients (pts). A randomized multicenter phase II study was conducted to compare fluorouracil, leucovorin, oxaliplatin with or without docetaxel (FLO vs. FLOT, respectively) in elderly pts with advanced gastric cancer (AGC). Our purpose was to identify pharmacogenetic markers as predictors of high grade PNP within this study. Methods: 143 pts were enrolled in this study. Pts. were numerically >65 years or numerically >59 years but classified biologically >65 years as defined by an Instrumental Activities of Daily Living score of <8. PNP was classified according to an oxaliplatin specific scale. Genotyping was performed using PCR-based RFLP or TaqMan®-based allelic discrimination. 20 polymorphisms in 13 genes being part of the metabolism of the applied drugs or DNA repair were analyzed. Statistical analyses were based on stepwise multivariate cox regression models and included genotypes and clinical parameters. Results: Median age was 71 years (range 60–83). Pts received in median 6 cycles of treatment (range 1–12). 130 pts were evaluable for PN at time of analyses. Of these, 68 received FLO and 62 received FLOT. Cumulative grade 3 PNP occurred in 49% of pts without a significant difference between FLO and FLOT receiving pts (44% and 53%, respectively, p=0.4). Genotypes of TS and MTHFR could be identified as independent risk factors for grade 3 PNP by multivariate analyses. Pts carrying a TS promoter genotype known to be associated with low TS expression (2R/2R, 2R/3RC, 3RC/3RC) were at higher risk for developing grade 3 PNP compared to pts without one of these genotypes (OR 3.0 [95%CI 1.27; 7.06], p=0.01). Pts carrying MTHFR1298AC or CC genotypes were also at higher risk for experiencing grade 3 PNP compared to pts with the wildtype MTHFR-1298AA genotype (OR 3.1 [95%CI 1.26; 7.60], p=0.01). In fact, 89% of pts that experienced grade 3 PNP were carriers of at least one of these risk genotypes. Conclusions: Polymorphisms of TS and MTHFR might be associated with grade 3 PNP in AGC pts receiving oxaliplatin based chemotherapy. No significant financial relationships to disclose.

scholarly journals Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer

2006 ◽  
Vol 94 (10) ◽  
pp. 1407-1411 ◽  
Author(s):  
J H Baek ◽  
J G Kim ◽  
S B Jeon ◽  
Y S Chae ◽  
D H Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study

A phase II study of oral S-1 with pharmacokinetics and pharmacogenomic investigation in advanced or recurrent gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4072-4072
Author(s):  
S. Y. Rha ◽  
H. C. Jeung ◽  
H. K. Kim ◽  
S. Y. Kim ◽  
S. Y. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Dose Escalation ◽  
Mononuclear Cells ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Asian Population ◽  
Genetic Changes ◽  
One Year

4072 Background: Present study describes the first phase II study of S-1 including pharmacokinetic and pharmacogenomic evaluation for extra-Japanese Asian population with advanced gastric cancer. Methods: Chemo-naive advanced gastric cancer with measurable disease was enrolled. Initial dose of S-1 was b.i.d. at 35, then 40 mg/m2 according to devised dosing method (range, 90–160 mg/day) for 28 days every 6 weeks. Pharmacokinetic study was performed after 28-day administration at cycle 1 and 3. Microarray based CGH was performed with genomic DNA from peripheral mononuclear cells to detect the toxicity-related genetic changes. Results: When first 31 patients were enrolled, protocol was amended to conduct the study by two steps for additional patients at 40 mg/m2 without dose escalation in initial 31 patients of 35 mg/m2, because these patients showed neither significant nor cumulative toxicity. Of 62 patients enrolled, median relative dose intensity was 0.99. Overall response rate was 19.3% (95% CI, 9.2–29.5). With 558-day follow-up duration, median TTP and OS were 126 and 264 days, respectively. One-year survival rate was 33.9%. Toxicity increased with dose escalation, but there was no grade 4 toxicity. The most common significant toxicity was anemia. Pharmacokinetics parameters were similar to those of Japanese population. In microarray-CGH, we selected 18 genes with different copy numbers of 13 amplified and 5 deleted genes in patients with anemia. Conclusions: Our phase II study showed the feasibility of S-1 in gastric cancer at the dose of 35 mg/m2, and we suggested that selected 18 genes might be candidate markers for predicting anemia with S-1 treatment. No significant financial relationships to disclose.

Phase II study of biweekly docetaxel and cisplatin combination chemotherapy in first-line advanced gastric cancer

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 15601-15601
Author(s):  
G. Quintero ◽  
M. Jorge ◽  
J. Casal ◽  
M. Salgado ◽  
S. Candamio ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
First Line

Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
E. Woell ◽  
R. Greil ◽  
W. Eisterer ◽  
M. Fridrik ◽  
B. Grünberger ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Line Setting

4538 Background: Patients (pts.) suffering from advanced gastric cancer have still a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1) we could show that the combination of oxaliplatin and irinotecan was well tolerated and showed an objective response rate of 58% (Anticancer Res 28:2901–2906, 2008). This chemotherapy regimen was tested in combination with cetuximab in a multicenter phase II trial. Methods: Oxaliplatin 85 mg/m2 biweekly and irinotecan 125 mg/m2 biweekly were combined with cetuximab 400 mg/m2 loading dose and subsequently weekly 250 mg/m2. 51 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma were treated in a first line setting. Median age: 62 years (range 19–79 years), PS 0: 25 patients, PS 1+2 26 patients, single metastatic site: 24 patients, multiple metastases: 27 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included neutropenia (35% of pts.), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3 and 4 toxicities included neutropenia in 9/1 pts., thrombocytopenia in 1/0 pts., anemia in 3/1 pts., nausea in 2/0 pts., and diarrhea in 7/2 pts. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of pts., in 7 pts. grade 3 neurotoxicity was observed. Acneiform skin rash grade 1 / 2 / 3 / 4 was reported in 31% / 20% / 6% / 2% of pts. respectively. 16 pts. went off-study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), progressive disease (n=3), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). 35 patients are assessable for response with 1 pt. (3%) showing a CR, 21 pts. (60%) a PR, 7 pts. (20%) a SD and PD in 6 pts. (17%). A disease control rate was achieved in 83%. Median time to progression was 24.8 weeks (n=29), median overall survival 38.1 weeks (n=32). Conclusions: The combination of oxaliplatin and irinotecan with cetuximab is feasible, safe and active in advanced gastric cancer. [Table: see text]

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