A phase II study of alternating chemotherapy with CDDP/ 5FU/ folinic acid (FA) and epirubicin (E)/ docetaxel (T) (CF-ET regimen) as first line therapy for patients (pts) with metastatic gastric cancer (MGC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14021-14021
Author(s):  
H. H. Kirchner ◽  
P. Panagiotou ◽  
O. Jordan ◽  
S. Hamann ◽  
M. Sosada
Keyword(s):  
Response Rate ◽  
Response Duration ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Median Response ◽  
First Line Therapy ◽  
Significant Efficacy ◽  
Grade 3 ◽  
Number Of Treatment

14021 Background: Active single agents in MGC are 5FU, CDDP, Anthracyclines, Taxanes and irinotecan. Combinations consisting of docetaxel, cisplatin, 5FU (TPF) and epirubicin, cisplatin, 5FU (ECF) have been investigated and both have shown activity and improvement of survival. However, the most efficient regimen is not yet defined. Methods: Chemotherapy-naive Patients with histologically confirmed MGC and measurable lesions were enrolled in this study. They received CDDP 35 mg/m2 iv on day (d) 1, 2, 15 and 16, 5FU 2000 mg/m2 continuous infusion (ci) d 1, 8, 15 and 22, FA 200 mg/m2 iv d 1, 8, 15 and 22 and E 60 mg/m2 d 29 and 43, T 60 mg/m2 d29 and 43 q d 57. Pts with at least one completed cycle were eligible. Objectives of this study were to evaluate the response rate, toxicity, PFS and OAS of CF-ET. Results: Between 2002 and 2005 34 pts (22 male and 9 female) aged 31 - 77 years (median 61) entered. The total number of treatment cycles was 56, mean 1.8 (1 - 5). 31 pts were eligible. 9 pts had complete response; 11 pts had partial response, 4 pts had stable disease, 7 pts had progressive disease and 3 pts were not evaluable. The overall response rate was 64.5%. The median response duration was 6.1 months (2 - 29.4). The overall survival was 11.4 months (2.6 - 43.6). Grade 3/4 toxicities were leukopenia 41/37.5%, neutropenia 16/82%, thrombocytopenia 23.2/0%, neutropenia related fever was observed in 4 cycles. No severe organ toxicities nor toxic death was seen. Conclusions: The alternating CF-ET regimen showed significant efficacy with prolonged survival. The ET-part of the regimen induced severe but manageable haematological toxicities. The results require further evaluation in a randomized phase III - trial. No significant financial relationships to disclose.

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.

1998 ◽  
Vol 16 (10) ◽  
pp. 3329-3334 ◽  
Author(s):  
N Masuda ◽  
K Matsui ◽  
S Negoro ◽  
N Takifuji ◽  
K Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Topoisomerase I ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Median Response ◽  
Grade 3

PURPOSE To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.

A Prospective, Randomized, Phase III Study of Melphalan 200 mg/m2 (MEL200) Versus Melphalan 100 mg/m2 (MEL100) in Newly Diagnosed Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 55-55 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Maria Teresa Petrucci ◽  
Antonietta Falcone ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Psychiatric Disease ◽  
High Dose ◽  
Free Survival ◽  
Grade 3

Abstract Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m2, MEL200) versus standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m2, MEL100) was also superior to the standard dose, but MEL100 has not been clinically compared with MEL200 in a randomized study. In a case-matched study, response rate and event-free survival of MEL200 were superior to MEL100, but overall survival (OS) was similar. In this prospective, randomized, phase III trial, we compared the efficacy and toxicity of MEL200 and MEL100. Between January 2002 and July 2006, 299 patients were enrolled. Inclusion criteria were previously untreated myeloma, aged < 65 and Durie and Salmon stage II or III. Exclusion criteria were abnormal cardiac function, respiratory disease, abnormal liver function, abnormal renal function, HBV, HCV, or HIV positivity, concomitant cancer or psychiatric disease. The institutional review board approved the protocol and written informed consent was obtained from all patients. All patients received: 2 dexamethasone-doxorubicin-vincristine debulking courses (doxorubicin 50 mg/m2 day 1, vincristine 1 mg day 1, dexamethasone 40 mg days 1, 2, 3, 4, each course repeated every 28 days), 2 cycles of cyclophosphamide (4 g/m2, day 1) plus G-CSF followed by stem cell harvest. The MEL200 group was conditioned with 2 cycles of melphalan 200 mg/m2 followed by stem cell reinfusion; the MEL100 group was conditioned with 2 courses of melphalan 100 mg/m2 followed by stem cell reinfusion. At the present, 246 patients, median age 57 (range 32–65), completed the assigned therapy and were evaluated for response, progression-free survival (PFS) and OS. One-hundred and twenty-four patients were randomized to MEL200 and 122 to MEL100. Patient characteristics were similar in both groups. Abnormal cytogenetics (13q deletion, t(4;14), t(11;14), p53) were 75% in MEL200 patients and 56% in MEL100 patients (p=0.05). Forty-six patients did not complete tandem MEL200; 36 patients did not complete tandem MEL100. The near complete response rate of MEL200 was superior to MEL100 (32% versus 18%, p=0.011), but partial response was 80% versus 71%, respectively (p=0.079). The median follow-up for censored patients was 26.5 months. The 3 years PFS was 51% in the MEL200 arm and 33% in the MEL100 arm (HR=0.81, 95% CI 0.55–1.21, p=0.31). The 3 years OS was 86% in the MEL200 group and 71% in the MEL100 group (HR=0.82, 95 CI 0.45–1.48, p=0.51). Duration of grade 4 neutropenia and thrombocytopenia was comparable in two arms, but MEL200 patients required more platelet transfusions (p=0.03). Grade 3–4 non-hematological adverse events were reported in 49% of the MEL200 patients and in 38% of the MEL100 patients (P=0.07). The most frequent grade 3–4 adverse events were infections (54% of MEL200 patients versus 45% of MEL100 patients, p=0.25), mucositis (31% of MEL200 patients versus 7% of MEL100 patients, p=0.002) and gastrointestinal toxicities (20% of MEL200 patients versus 14% of MEL100 patients, p=0.3). In conclusion, MEL200 resulted in a significantly higher near complete response rate but this did not translate in a superior PFS and OS.

5-Azacytidine in 82 Low/Intermediate-1 IPSS Risk Myelodysplastic Syndromes: Results from the Italian Patient Named Program

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2680-2680
Author(s):  
Pellegrino Musto ◽  
Luca Maurillo ◽  
Alessandra Spagnoli ◽  
Antonella Gozzini ◽  
Flavia Rivellini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Response Rate ◽  
Previous Treatment ◽  
Response Duration ◽  
Complete Response ◽  
Median Number ◽  
Phase Iii ◽  
Fixed Dose ◽  
Female Ratio

Abstract 5-azacytidine (AZA) significantly prolonged overall survival in higher-risk patients with myelodysplastic syndromes (MDS) in a large, international, randomized, phase III trial (AZA-001). However, data about efficacy and safety of AZA in lower risk MDS are less consistent and only few small studies have addressed this topic. Among a total of 246 MDS treated with AZA in 31 different Italian Institutions since 2005 within to a national patient named program, we evaluated 82 patients scored as low/int-1 IPSS risk MDS. Median age was 68 years (range 34–85), male/female ratio 50/32. According to WHO classification, there were 21 RA/RARS, 4 5q-syndromes, 20 RCMD, 24 RAEB-1, 5 RAEB-2, 4 CMMoL, and 4 MDS unclassified. Median time from diagnosis was 27 months (range 1–132). Sixty-eight patients (82.9%) were transfusion-dependent, sixty (74%) had received a prior treatment, mostly with erythropoiesis stimulating agents. AZA was administered as single drug in 61 patients (74.4%), while in the remaining subjects it was variously combined with growth factors, valproic acid or other agents. Forty-eight patients (58.5%) received a “standard” AZA dose of 75 mg/sqm/d s.c., thirty-four (41.5%) a fixed dose of 100 mg/d s.c. Single cycle treatment duration was 7 days in 45 patients (54.9%), &lt; 7 days in 32 patients (39%), &gt; 7 days in 3 patients (3.7%), unknown in 2 patients (2.4%). The median number of monthly cycles was 6 (range 1–21), and 63 patients (76.8%) completed at least 4 cycles. The most relevant toxicities observed (grade 3–4) were represented by myelosuppression (22%) and infections (6%). According to 2006-updated IWG criteria, overall response rate was 39% (47.5% in patients who had completed at least 4 cycles). In particular, complete response, partial response and hematological improvement occurred in 12.2%, 8.5% and 18.3% of patients (15.8%, 11.1% and 20.6% in those who were treated with at least 4 cycles), respectively. Stable or progressive disease was observed in 29.3%/25.6% and 30.2%/22.2% of patients receiving less than or at least 4 cycles, respectively. Response duration ranged from 1 to +21 months. There were no significant differences in response rate according to dose and schedule employed, although a slight trend in favour of 75 mg/sqm vs 100 mg fixed dose was seen (45.8% vs 29.4%, respectively). There was also no difference in the percentages of response according to age, previous treatment and transfusion dependence. Overall survival at 2 years was 62%. A survival benefit emerged for responding patients, compared to non responders (82% vs 57%) (p=0.015). A favourable trend was also observed for transfusion-independent patients, while age, pre-treatment and AZA dose did not influence survival. These data indicate that AZA may be safe and effective for a subset of patients with low/int-1 IPSS risk MDS, resistant or not suitable for alternative treatments. The efficacy may improve if at least 4 cycles are administered.

Bortezomib Added to R-CVP Is Safe and Effective for Previously Untreated Advanced-Stage Follicular Lymphoma: A Phase II Study by the National Cancer Institute of Canada Clinical Trials Group

2011 ◽  
Vol 29 (25) ◽  
pp. 3396-3401 ◽  
Author(s):  
Laurie H. Sehn ◽  
David MacDonald ◽  
Sheldon Rubin ◽  
Guy Cantin ◽  
Morel Rubinger ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Complete Response Rate ◽  
Standard Dose ◽  
Complete Response ◽  
Phase Iii ◽  
High Risk Population ◽  
Advanced Stage ◽  
Grade 3

Purpose Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL. Patients and Methods This is a phase II multicenter trial adding bortezomib (1.3 mg/m2 days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed. Results Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%). Conclusion The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.

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.

A phase II study of oxaliplatin with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced or metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14052-14052
Author(s):  
H. Kim ◽  
H. Kwon ◽  
S. Y. Oh ◽  
B. G. Seo ◽  
S. G. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Continuous Infusion ◽  
Low Dose ◽  
Overall Response Rate ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

14052 Background: To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX-4), as a first-line therapy for patients with advanced or recurrent gastric cancer. Methods: Between January 2003 and March 2005, forty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at day 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU a 400 mg/m2 bolus and 22 hour continuous infusion of 600 mg/m2 5-FU at day 1–2. This treatment was repeated in 2 week intervals. Results: There was one patient (2.2%) demonstrated a complete response. Twenty patients (44.4%) showed a partial response. Overall response rate was 46.6%. Ten patients (22.2%) showed a stable disease and fourteen patients (31.1%) progressed during the course of the treatment. The median time to progression and overall survival time were 7.73 months (95% CI: 3.6–11.86 months) and 11.17 months (95% CI: 9.06–13.28 months) from the start of the chemotherapy, respectively. A total of 247 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1–2 anemia (39.7%), neutropenia (30.4%), grade 3–4 neutropnenia (10.9%) and thrombocytopenia (9.3%).There were 12 cycles of neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%), grade 1–2 neuropathy (13.4%) and grade 3 diarrhea (2.2%). There was no treatment related death. Conclusions: The modified FOLFOX-4 regimen is safe and effective regimen as a first line therapy in advanced or metastatic gastric cancer. No significant financial relationships to disclose.

A phase II of high dose capecitabine plus irinotecan for patients with advanced or metastatic gastric cancer: preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14086-14086
Author(s):  
S. Oh ◽  
H. Seo ◽  
H. Sung ◽  
I. Choi ◽  
S. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Dose Intensity ◽  
Response Duration ◽  
Metastatic Gastric Cancer ◽  
Survival Duration ◽  
High Dose ◽  
Synergistic Activity ◽  
Median Response

14086 Background: Capecitabine is the prodrug of 5-FU to generate maximal tumor activity in tumor site and/or improve the tolerability, has demonstrated the synergistic activity with irinotecan in some solid cancers . Previous study showed the dose intensification of capecitabine increased the response rate with comparable toxicities in metastatic colorectal cancer. We conducted this study to ascertain the efficacy and toxicity of irinotecan and high dose capecitabine combination chemotherapy for chemotherapy-naïve advanced or metastatic gastric cancer. Methods: Patients who were advanced or metastatic gastric cancer and have not received any chemotherapeutic drug except adjuvant chemotherapy, received irinotecan 130mg/m2 intravenously (i.v) for 90 min on day 1 and day 15 and capecitabine 3500 mg/day, divided two, was administered for 7 consecutive days from day1 and day 15, and this was followed by a 7-day drug-free interval. Results: 35 eligible patients were enrolled in this study from Nov/2003 to Nov/2006. 14 women and 21 men: median age 51 ys, range 27–81. A total 106 courses were administered, and median number of courses per patient was three (range, 1–8). Intent-to-treatment analysis showed the one complete response (2.9%), 13 partial responses (37.1%), 9 stable disease (25.7%), 8 progressive disease (22.9%) and 4 non-evaluable patients (11.4%). The overall response rate was 40% (95% CI: 23.5–56.5). Grade 3–4 toxicities were: neutropenia 8 (22.8%), nausea/vomiting 2 (5.7%), stomatitis 1 (2.9%), ischemic colitis 1 (2.9%), anemia 3 (8.6%), diarrhea 2 (5.7%), alopecia 3 (8.6%). Treatment related death was shown at one patient due to pneumonia. Dose intensity of irinotecan and capecitabine was 94% and 93%, respectively. Median time to progression was 4 months (range, 0.5 - 11 months), median survival duration was 8.5 months (range, 0.5 - 45 months), and median response duration was 2.5 months (range, 0.5 - 9 months). Conclusions: We suggest that irinotecan and high dose capecitabine combination chemotherapy is the tolerable regimen to advanced or metastastic gastric cancer with promising activity. No significant financial relationships to disclose.

Up-Front Window Trial of Topotecan in Previously Untreated Children and Adolescents With Metastatic Rhabdomyosarcoma: An Intergroup Rhabdomyosarcoma Study

2001 ◽  
Vol 19 (1) ◽  
pp. 213-219 ◽  
Author(s):  
Alberto S. Pappo ◽  
Elizabeth Lyden ◽  
John Breneman ◽  
Eugene Wiener ◽  
Lisa Teot ◽  
...  
Keyword(s):  
Partial Response ◽  
Response Rate ◽  
Complete Response ◽  
High Response Rate ◽  
Phase Iii ◽  
Continuation Therapy ◽  
Common Grade ◽  
Front Window ◽  
Phase Iii Trials ◽  
Grade 3

PURPOSE: To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m2 of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m2, dactinomycin 1.5 mg/m2, and cyclophosphamide 2.2 g/m2 (VAC) and vincristine 1.5 mg/m2, topotecan 0.75 mg/m2 daily × 5, and cyclophosphamide 250 mg/m2 daily × 5. Patients who did not respond to topotecan received continuation therapy with VAC alone. RESULTS: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival. CONCLUSION: The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.

Phase III Study of Docetaxel and Cisplatin Plus Fluorouracil Compared With Cisplatin and Fluorouracil As First-Line Therapy for Advanced Gastric Cancer: A Report of the V325 Study Group

2006 ◽  
Vol 24 (31) ◽  
pp. 4991-4997 ◽  
Author(s):  
Eric Van Cutsem ◽  
Vladimir M. Moiseyenko ◽  
Sergei Tjulandin ◽  
Alejandro Majlis ◽  
Manuel Constenla ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Risk Reduction ◽  
Cancer Patients ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Iii ◽  
First Line Therapy ◽  
Grade 3 ◽  
Gastric Cancer Patients

Purpose In the randomized, multinational phase II/III trial (V325) of untreated advanced gastric cancer patients, the phase II part selected docetaxel, cisplatin, and fluorouracil (DCF) over docetaxel and cisplatin for comparison against cisplatin and fluorouracil (CF; reference regimen) in the phase III part. Patients and Methods Advanced gastric cancer patients were randomly assigned to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 (day 1) plus fluorouracil 750 mg/m2/d (days 1 to 5) every 3 weeks or cisplatin 100 mg/m2 (day 1) plus fluorouracil 1,000 mg/m2/d (days 1 to 5) every 4 weeks. The primary end point was time-to-progression (TTP). Results In 445 randomly assigned and treated patients (DCF = 221; CF = 224), TTP was longer with DCF versus CF (32% risk reduction; log-rank P < .001). Overall survival was longer with DCF versus CF (23% risk reduction; log-rank P = .02). Two-year survival rate was 18% with DCF and 9% with CF. Overall response rate was higher with DCF (χ2 P = .01). Grade 3 to 4 treatment-related adverse events occurred in 69% (DCF) v 59% (CF) of patients. Frequent grade 3 to 4 toxicities for DCF v CF were: neutropenia (82% v 57%), stomatitis (21% v 27%), diarrhea (19% v 8%), lethargy (19% v 14%). Complicated neutropenia was more frequent with DCF than CF (29% v 12%). Conclusion Adding docetaxel to CF significantly improved TTP, survival, and response rate in gastric cancer patients, but resulted in some increase in toxicity. Incorporation of docetaxel, as in DCF or with other active drug(s), is a new therapy option for patients with untreated advanced gastric cancer.

Front-Line Transplantation Program With Lenalidomide, Bortezomib, and Dexamethasone Combination As Induction and Consolidation Followed by Lenalidomide Maintenance in Patients With Multiple Myeloma: A Phase II Study by the Intergroupe Francophone du Myélome

2014 ◽  
Vol 32 (25) ◽  
pp. 2712-2717 ◽  
Author(s):  
Murielle Roussel ◽  
Valérie Lauwers-Cances ◽  
Nelly Robillard ◽  
Cyrille Hulin ◽  
Xavier Leleu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Residual Disease ◽  
Phase Ii Study ◽  
Sensory Neuropathy ◽  
Complete Response ◽  
Phase Iii ◽  
Transplantation Program ◽  
Significant Efficacy ◽  
Grade 3

Purpose The three-drug combination of lenalidomide, bortezomib, and dexamethasone (RVD) has shown significant efficacy in multiple myeloma (MM). The Intergroupe Francophone du Myélome (IFM) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM. Patients and Methods In this phase II study, 31 symptomatic patients age < 65 years were enrolled to receive three RVD induction cycles followed by cyclophosphamide harvest and transplantation. Patients subsequently received two RVD consolidation cycles and 1-year lenalidomide maintenance. Results Very good partial response rate or better at the completion of induction, transplantation, and consolidation therapy was 58%, 70%, and 87%, respectively. Maintenance upgraded responses in 27% of patients. Overall, 58% of patients achieved complete response, and 68% were minimal residual disease (MRD) negative by flow cytometry. The most common toxicities with RVD were neurologic and hematologic, including grade 1 to 2 sensory neuropathy (55%), grade 3 to 4 neutropenia (35%), and thrombocytopenia (13%). Two basal cell carcinomas in the same patient and one case of breast cancer were observed. There was no treatment-related mortality. With a median follow-up of 39 months, estimated 3-year progression-free and overall survival were 77% and 100%, respectively. None of the patients who achieved MRD negativity relapsed. Conclusion The transplantation program with RVD induction and consolidation followed by lenalidomide maintenance produced high-quality responses and showed favorable tolerability in patients with newly diagnosed MM. Overall, 68% of patients achieved MRD negativity; none of these patients relapsed. This program is being evaluated in the ongoing IFM/Dana-Farber Cancer Institute 2009 phase III study.

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