Phase II trial of uracil and tegafur plus oral leucovorin: an effective oral regimen in the treatment of metastatic colorectal carcinoma.

1994 ◽  
Vol 12 (11) ◽  
pp. 2296-2300 ◽  
Author(s):  
R Pazdur ◽  
Y Lassere ◽  
V Rhodes ◽  
J A Ajani ◽  
S M Sugarman ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Oral Mucositis ◽  
Rest Period ◽  
Complete Response ◽  
Phase Iii ◽  
Significant Activity ◽  
Metastatic Colorectal Carcinoma ◽  
Oral Regimen ◽  
Phase Iii Study ◽  
Grade 3

PURPOSE To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma. PATIENTS AND METHODS Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy. RESULTS Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2%; 95% confidence interval, 28% to 58%). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). CONCLUSION UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.

scholarly journals Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 145-145 ◽  
Author(s):  
Mathias J. Rummel ◽  
Christina Balser ◽  
Ulrich Kaiser ◽  
Hans Peter Böck ◽  
Martina Beate Stauch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Indolent Lymphomas

Abstract Introduction: Fludarabine plus rituximab (F-R) is an established treatment option for patients (pts) with relapsed/refractory follicular lymphoma (FL), other indolent lymphoma, or mantle cell lymphoma (MCL). To further improve the treatment in this setting we initiated in 2003 a multicenter, randomized phase III study to compare the efficacy and safety of bendamustine plus rituximab (B-R) versus F-R for pts with relapsed FL, other indolent lymphomas or MCL. Patients and Methods: 230 pts in need of treatment were randomized to rituximab 375 mg/m² (day 1) plus either bendamustine 90 mg/m² (days 1+2) or fludarabine 25 mg/m² (days 1–3) q 28 days for a maximum of 6 cycles. Prophylactic use of antibiotics or granulocyte-colony stimulating factor (G-CSF) was not generally recommended; however, in case of severe granulocytopenia, G-CSF use was permitted. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and complete response rate (CR). The protocol was amended in 2006 to allow rituximab maintenance therapy (rituximab 375 mg/m2 q 3 months for up to 2 years) in both arms, following regulatory approvals in this setting. Results: A total of 219 pts were evaluable for the analysis (114 B-R; 105 F-R). There were no significant differences between arms for patient characteristics, including age, stage, LDH, IPI, FLIPI, bone marrow infiltration, and extranodal involvement. Most pts had stage IV (71.6% B-R; 60.6% F-R) or stage III disease (21.1% B-R; 25.3% F-R). Median patient age was 68 yrs (range 38–87). Patients had received a median of 1 prior therapy (range 1–7). Histological subtypes were distributed equally between the B-R and F-R arms: follicular, 45.9% and 47.5%, respectively; Waldenström’s Macroglobulinemia, 11.9% and 11.1%; MCL, 20.2% and 21.2%; other indolent lymphomas, 23% and 20.2%. A median of 6 cycles were given in both treatment arms, with 75.2% and 53.4% of B-R and F-R pts receiving 6 cycles, respectively. At the time of this analysis (June 2014), the median observation time was 96 months. The ORR was significantly higher with B-R than with F-R (83.5% vs. 52.5%, respectively; p< 0.0001). The CR rate with B-R was also significantly higher than that with F-R (38.5% vs. 16.2%; p=0.0004). Median PFS was significantly prolonged with B-R compared with F-R (34 vs. 12 months; hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.38–0.72; p<0.0001). The longer PFS translated into a survival benefit with a significantly longer median overall survival in the B-R group than in the F-R group (110 vs. 49 months; HR 0.64, 95% CI 0.45–0.91; p=0.0125) comprising 55 and 71 deaths in the B-R and F-R groups, respectively. There were no significant differences in the rates of alopecia, stomatitis, erythema, allergic reactions, peripheral neuropathy, or infectious episodes between groups. Hematologic toxicities were also similar between arms: 8.9% grade 3/4 neutropenia with B-R vs. 9.1% with F-R; 11.8% grade 3/4 leukocytopenia with B-R vs. 12.4% with F-R. The overall incidence of serious adverse events was similar for the B-R and F-R groups (17.4% and 22.2%, respectively). 17 pts (14.9%) developed a secondary neoplasia after B-R compared with 16 pts (15.2%) after F-R. Of these, 5 pts in the B-R group, and 3 pts in the F-R group developed a secondary hematological neoplasia (2 AML [1 AML M4], 1 CML, 1 DLBCL, and 1 HD after B-R; and 2 AML M4, and 1 MDS after F-R). An unplanned subanalysis showed that rituximab maintenance therapy significantly prolonged overall survival (HR 0.38, 95% CI 0.32-0.71; p=0.0003) and PFS (HR 0.35, 95% CI 0.31-0.62; p< 0.0001) in the small group of 40 pts who received this treatment (23 B-R, 17 F-R) compared with those who did not. Although the numbers are too small in this non-randomized comparison to draw validated conclusions, these results appear to confirm the favorable role of rituximab maintenance. Conclusions: B-R was more effective than F-R in this setting of relapsed FL, other indolent lymphomas and MCL due to higher overall and complete response rates, a longer PFS, and an improved OS. These data confirm the high anti-lymphoma activity of B-R. Disclosures Off Label Use: Indication and dosage of bendamustine.

Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

2012 ◽  
Vol 30 (20) ◽  
pp. 2475-2482 ◽  
Author(s):  
Laurent Garderet ◽  
Simona Iacobelli ◽  
Philippe Moreau ◽  
Mamoun Dib ◽  
Ingrid Lafon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Rest Period ◽  
Working Party ◽  
Complete Response ◽  
Phase Iii ◽  
Triple Combination ◽  
Blood And Marrow Transplantation ◽  
Duration Of Response ◽  
Grade 3

Purpose This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). Results Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P = .001), and the median duration of response was longer (17.9 v 13.4 months; P = .04). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. Conclusion VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.

Phase II study of cisplatin, epirubicin, oral UFT, and leucovorin as first-line chemotherapy for metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14049-14049
Author(s):  
E. Idelevich ◽  
N. Karminsky ◽  
M. Dinerman ◽  
R. Katsenelson ◽  
N. Ben Zvi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Rest Period ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Significant Activity ◽  
Disease Stabilization ◽  
Grade 3

14049 Background: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with cisplatin, epirubicin, oral UFT and leucovorin in patients (Pts) with metastatic gastric cancer. Methods: Pts with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day (d)1, UFT 300 mg/m2 was administered in conjunction with oral leucovorin 30 mg/day in divided daily doses d 1–22, followed by a 7-day rest period. Results: Thirty-nine pts were enrolled in this study. Two achieved a complete response and 13 a partial response, giving an overall response rate of 38.5%. Disease stabilization was achieved in further 16 pts (41%). Median time to progression and median survival were 6.4 and 10.7 months respectively. Grade 3/4 neutropenia, anemia, throbocytopenia, occurred in 10%, 5%, and 2% of pts respectively, and febrile neutropenia occurred in 7 pts (one episode each). Grade 3 diarrhea occurred in 5% of the pts. There were no treatment related deaths. Conclusions: Cisplatin, epirubicin, and oral UFT plus leucovorin, a convenient outpatient regimen, has significant activity and tolerable toxicities in pts with metastatic gastric carcinoma. No significant financial relationships to disclose.

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