A phase II study of weekly paclitaxel and doxifluridine (an intermediate metabolite of capecitabine) combination chemotherapy for advanced/recurrent gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4593-4593
Author(s):  
I. Takeyoshi ◽  
F. Makita ◽  
Y. Tanahashi ◽  
S. Iwazaki ◽  
S. Nakamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Single Agent ◽  
Dose Intensity ◽  
Intention To Treat ◽  
First Line Therapy ◽  
Line Therapy ◽  
Recurrent Gastric Cancer ◽  
Intermediate Metabolite

4593 Background: Paclitaxel and doxifluridine (5’-DFUR; an intermediate metabolite of capecitabine), which have distinct mechanisms of action and toxicity profiles, each have considerable single-agent activity in gastric cancer. A synergistic interaction between these two drugs was suggested from the taxane-induced upregulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. Therefore, this study evaluated the antitumor activity and toxicities of paclitaxel and 5’-DFUR in combination in patients with advanced/recurrent gastric cancer (AGC) Methods: Patients with histologically confirmed AGC, which was unresectable or metastatic, PS 0–2, and over 20 years old were eligible for this study. The treatment included paclitaxel 80 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and doxifluridine 533 mg/m2 p.o. on days 1–5/week until there was disease progression or the appearance of unacceptable toxicity. Results: Between April 2003 and May 2006,104 patients were enrolled in this study. Their median age was 67.0 years (range: 36–82) and 87 patients were male. Forty-three patients had advanced gastric cancer and 61 had recurrent gastric cancer. After a median of 3 (range: 1- 21) cycles of chemotherapy, 104 patients were evaluated for toxicity and 93 patients were evaluated for response. In the intention-to-treat analysis, the overall response rate was 32.3% (95% C.I., 22.8–41.8%), including 2 CR, 28 PRs, 37 SDs, 16 PDs, and 10 NEs. The first-line therapy involved 48 patients (primary advanced or surgery alone) in whom the response rate was 41.7% (95% C.I., 27.7–55.6%). The second-line therapy involved 40 patients (72.5% TS-1 failure) in whom the response rate was 22.5% (95% C.I., 9.6–35.4%). The median overall survival was 287 days. The actual dose intensity was 81.7% (85/104) of the planned dose during the first two cycles for both drugs. Commonly observed grade 3/4 adverse events were leukopenia (13.5%), anorexia (3.8%), fatigue (3.8%), and diarrhea (2.9%).There was no neutropenic fever or treatment-related death. Conclusions: These data suggest that Paclitaxel and 5’-DFUR combination chemotherapy is a well tolerated convenient out-patient combination with very promising efficacy for AGC. No significant financial relationships to disclose.

A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15050-15050
Author(s):  
S. Yoshino ◽  
T. Nishimura ◽  
S. Hazama ◽  
M. Oka ◽  
H. Ozasa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Outpatient Setting ◽  
Eligibility Criteria ◽  
Line Therapy ◽  
Recurrent Gastric Cancer

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.

Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Silvia Rivas-Vera ◽  
Enrique Baez ◽  
Pedro Sobrevilla-Calvo ◽  
Severiano Baltazar ◽  
Francisco Tripp ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Disease Free Survival ◽  
First Line ◽  
Free Survival ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

Abstract Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.

scholarly journals Phase II Trial of a Novel Paclitaxel Schedule As Single-Agent, First-Line Therapy for HER-2/neu–Negative Metastatic Breast Cancer: A Community-Based Study

2006 ◽  
Vol 2 (6) ◽  
pp. 268-273
Author(s):  
David Loesch ◽  
Nicholas Robert ◽  
Stephen Jones ◽  
Maha Elkordy ◽  
Des Ilegbodu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Group Performance ◽  
Single Agent ◽  
Metastatic Breast ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2

Purpose To determine the response rate (RR), progression-free survival (PFS), and toxicity in patients with HER-2/neu–negative metastatic breast cancer treated with first-line paclitaxel in a de-escalating dosing schedule. Patients and Methods Between August 1999 and December 2000, 73 patients were enrolled. Paclitaxel was administered on day 1 (175 mg/m2) and on days 8 and 15 (80 mg/m2 each) in each 4-week cycle (1 week of rest). Doses were de-escalated with the aim of reducing toxicity. An Eastern Cooperative Oncology Group performance status of 0, 1, or 2 was found in 55%, 41%, and 4% of patients, respectively. Median age was 59 years (range, 38 to 84 years), and 86% of patients had received prior surgery; 60%, adjuvant chemotherapy; and 59%, radiation therapy. Results Based on an intention-to-treat analysis (N = 73), there were five patients with a complete response (6.8%), 16 with a partial response (21.9%), 17 with stable disease (23.3%), and 23 with progressive disease (31.5%) for an RR of 28.7%. Twelve patients (16.4%) were not assessable for response due to toxicity (seven patients, mainly neuropathy), withdrawal of consent (two patients), early death (two patients), or noncompliance (one patient). Median PFS was 6.5 months (range, < 1 to 36.1 months), median survival was 22.8 months (range, < 1 to 36.1 months), and median duration of response was 8.8 months (range, 3.0 to 31.8 months). Patients (n = 72) were evaluated for toxicity. Grade 3 to 4 treatment-related toxicities occurring in more than 5% of patients included neutropenia (22.2%), neuropathy (18.1%), fatigue (6.9%), and leukopenia (5.6%). Conclusion In a unique de-escalating schedule, this study of single-agent paclitaxel produced a response rate similar to other single-agent paclitaxel schedules, in first-line therapy for metastatic breast cancer, published in the literature. However, this schedule is not recommended for the therapy of metastatic breast cancer because of the higher rate of toxicity.

A combination phase I study of biweekly docetaxel and 5’-DFUR in patients with unresectable or recurrent gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14115-14115
Author(s):  
S. Yoshino ◽  
M. Oka ◽  
S. Hazama ◽  
R. Shimizu ◽  
T. Yamamoto
Keyword(s):  
Gastric Cancer ◽  
Dose Level ◽  
Response Rate ◽  
Single Agent ◽  
Fixed Dose ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Prior Chemotherapy ◽  
Recurrent Gastric Cancer ◽  
Level 1

14115 Background: Docetaxel (DOC) and 5’-DFUR (an intermetamolite of capecitabine) have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between DOC and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase. The objectives of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD) of the combination therapy of biweekly DOC and 5’-DFUR. The DLT was set in low grade to treat the patients in the outpatient clinic. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer, no requirement of prior chemotherapy, a performance status of 0–2, adequate organ function and written informed consent. DOC was administered by 1-hour intravenous infusion (level 1, 2, 3, 4: 30, 35, 40, 45 mg/m2) biweekly for 4 weeks. 5’-DFUR was administered orally at a fixed dose of 600mg/body everyday. Toxicity and efficacy were evaluated during the 2 cycles for 8 weeks. Three or 6 patients were enrolled at each dose level. Administration of DOC was skipped in the event of grade 2 hematologic toxicity. DLT was defined as grade 3 hematologic toxicity, grade 2 non-hematologic toxicity. The MTD was defined as the dose level at which at least two of three patients or three of six patients presented with DLT. Results: Twelve patients with a median age of 58 years (range, 29 to 75) were enrolled in this study. Five patients have received prior chemotherapy. Eight patients were unresectable and 4 had recurrent tumors. At level 1 (n=3), 2 (n=3), 3 (n=3), no patients developed DLT. Two patients developed DLT at level 4 (n=3). All DLT was neutropenia. Only 1 developed grade 4 neutropenia at level 4. Non-hematological toxicity was uncommon. Level 4 was determined as the MTD. Of 8 evaluable patients, responses included 4 PR, 3 SD and 1 PD for an overall response rate of 50%. Conclusions: The MTD of DOC in this combination is 45 mg/m2 and the RD is 40 mg/m2. This regimen is well-tolerated with high response rate in outpatient setting. A phase II study is necessary to evaluate the response of this regimen. No significant financial relationships to disclose.

Phase II study of S-1 in combination with paclitaxel as a first-line treatment for patients with advanced/recurrent gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15615-e15615
Author(s):  
U. Toh ◽  
H. Yamana ◽  
K. Koufuji ◽  
T. Mine ◽  
K. Aoyagi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Single Agent ◽  
First Line ◽  
Curative Gastrectomy ◽  
Intention To Treat ◽  
Recurrent Gastric Cancer ◽  
Grade 3 ◽  
Treat Analysis

e15615 Background: Taxanes and S-1 have been shown to be effective in patients with advanced gastric cancer and they have a considerable single-agent activity, respectively. We evaluated the combination of paclitaxel and S-1 as first-line chemotherapy for advanced or recurrent gastric cancer (AGC). Methods: All patients with histologically confirmed AGC with unresectable or metastatic diseases, measurable lesions, PS 0–2, age between 18 and 75, and no contraindication to chemotherapy were eligible in this study. Prior adjuvant chemotherapy finished at least 6 months before enrollment was allowed. Treatment included S-1 80 mg/m2 p.o. twice daily on days 1–14 and paclitaxel 60 mg/m2 i.v. on day 1, 8, 15 with a 2-week interval until disease progression or unacceptable toxicities. Results: Between MAY 2004 and Match 2008, total 20 pts were enrolled in this study. The median age was 56.5 years (range, 38–73). Nine pts had recurrent disease after previous curative gastrectomy and 8 had previous adjuvant chemotherapy. After a median 4 (range, 1–9) cycles of chemotherapy, 12 pts were evaluable for toxicity and 20 pts for response. In intention-to-treat analysis, the overall response rate was 62.9% (95% C.I., 36.2–69.6%), including 0 CR, 6 PRs, 8 SDs, and 6 PDs. After a median follow-up of 8.6 months (range, 0.9–17.9), median time to progression was 6.3 months (95% C.I., 3.6–6.9) and median overall survival was 11.6 months (95% C.I., 8.5–20.7). Commonly observed grade 3/4 adverse events were neutropenia (40% of patients), anemia (10%). There was no neutropenic fever or treatment-related death. Conclusions: The combination of paclitaxel and S-1 appear to have well efficacy, manageable toxicity and is well tolerated in patients with AGC. Further studies of this combination should be considered. No significant financial relationships to disclose.

A phase II study of S-1 and oxaliplatin (SOx) combination chemotherapy as a first-line therapy for patients with advanced gastric cancer

2010 ◽  
Vol 30 (1) ◽  
pp. 350-356 ◽  
Author(s):  
Sung Yong Oh ◽  
Hyuk-Chan Kwon ◽  
Sang-Ho Jeong ◽  
Young-Tae Joo ◽  
Young-Joon Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy
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