Randomized phase II trial of irinotecan plus cisplatin (IP) versus irinotecan, cisplatin plus etoposide (IPE) every three weeks in patients with extensive disease small cell lung cancer (ED-SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7087-7087
Author(s):  
I. Sekine ◽  
H. Nokihara ◽  
K. Takeda ◽  
Y. Nishiwaki ◽  
K. Nakagawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Body Weight Loss ◽  
Complete Response ◽  
Phase Iii ◽  
Antitumor Effects ◽  
Pilot Studies ◽  
Randomized Phase Ii ◽  
Phase Iii Trials ◽  
Grade 3

7087 Background: A promising complete response rate and median survival time were obtained in our previous phase II study of IPE chemotherapy repeated every 4 weeks in patients with ED-SCLC, but the infusion of irinotecan on day 15 was omitted in 77% of patients. Methods: The objective was to evaluate toxicities and antitumor effects of IP and IPE regimens every 3 weeks and to select the arm for subsequent phase III trials. The primary endpoint was overall survival. Previously untreated ED-SCLC patients aged between 20 and 70 years old with a performance status (PS) of 0–2 were randomized to receive either IP (I 60 mg/m2 days 1, 8 and P 60 mg/m2 day 1) or IPE (the same dose of IP and E 50 mg/m2 days 1–3 with G-CSF support) every 3 weeks for 4 cycles. The projected sample size was 110 patients (Liu’s Selection design for pilot studies on survival). Results: From March 2003 to May 2005, 53 patients (43 males/10 females, median age 63) were randomized to IP and 57 patients (48 males/9 females, median age 62) to IPE. Body weight loss and PS were well balanced between the arms. Full cycles were administered in 75% of patients in the IP and in 67% in the IPE arm. Dose reduction was required in 17% of patients in the IP and 28% in the IPE arm. Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 53%, 34% and 4% of patients in the IP, and 93%, 45%, and 23% of patients in the IPE arm, respectively. Grade 3–4 infection, malaise, anorexia, and diarrhea were noted in 15%, 2%, 0%, and 15% of patients in the IP, and 30%, 11%, 15%, and 24% of patients in the IPE arm, respectively. No treatment related death occurred. Complete and partial responses were noted in 8% and 68% of patients in the IP, and 11% and 75% of patients in the IPE arm, respectively. Conclusion: Toxicity was more severe, but tumor responses seemed better in the IPE arm. The survival analysis will be carried out in April 2006. No significant financial relationships to disclose.

Randomized phase II/III trial comparing gemcitabine/carboplatin (GC) and methotrexate/carboplatin/vinblastine (M-CAVI) in patients (pts) with advanced urothelial cancer (UC) unfit for cisplatin-based chemotherapy (CHT): Phase III results of EORTC study 30986.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA4519-LBA4519 ◽  
Author(s):  
M. De Santis ◽  
J. Bellmunt ◽  
G. Mead ◽  
J. M. Kerst ◽  
M. G. Leahy ◽  
...  
Keyword(s):  
Renal Function ◽  
Phase Ii ◽  
Impaired Renal Function ◽  
Performance Status ◽  
Primary Objective ◽  
Error Rates ◽  
Phase Iii ◽  
Logrank Test ◽  
Randomized Phase Ii ◽  
Grade 3

LBA4519 Background: About 50% of pts with advanced UC are not eligible for cisplatin based CHT (“unfit”) due to impaired renal function, performance status (PS) or comorbidity. This is the first randomized phase II/III trial comparing two chemotherapy regimens in this pts group. Methods: The primary objective of the phase III part of this study was to compare the overall survival (OS) of CHT naïve pts with measurable disease and an impaired renal function (GFR<60 but >30 ml/min) and/or PS 2 who were randomized to receive either GC (G 1000 mg/m2 d1 and 8 and C AUC 4.5) q21 days or M-CAVI (M 30 mg/m2 d1 and 15 and 22, C AUC 4.5 d1 and VI 3 mg/m2 d1 and 15 and 22) q28 days. In order to detect an increase of 50% in median survival on GC compared to M-CAVI (13.5 versus 9 months) based on a two sided logrank test at error rates alpha=0.05 and beta=0.20, 225 pts were required. Secondary endpoints were overall response rate (ORR) and progression free survival (PFS). Results: 238 pts, 119 in each arm, were randomized between January 2001 and March 2008 by 29 institutions. The median follow-up is 4.5 years. Two pts were ineligible and two other pts never started treatment. Best ORRs (CR + PR) were 41.2% (36.1% confirmed response) on GC versus 30.3% (21.0% confirmed response) on M-CAVI (p = 0.08). Median OS was 9.3 months on GC and 8.1 months on M-CAVI (p = 0.64). There was no difference in PFS between the two arms (p = 0.78). OS, PFS and ORR were similar in each of the risk groups (reason unfit for cisplatin and Bajorin risk group). Severe acute toxicity (SAT) (death, grade 4 thrombocytopenia with bleeding, or grade 3/4 renal toxicity, neutropenic fever or mucositis) was observed in 9.3% of pts on GC (2 toxic deaths) and 21.2% on M-CAVI (4 toxic deaths). The most common grade 3/4 toxicities were leucopenia (44.9%, 46.6%), neutropenia (52.5%, 63.5%), febrile neutropenia (4.2%, 14.4%), thrombocytopenia (48.3%, 19.4%), and infection (11.8%, 12.7%) on GC and M-CAVI, respectively. Conclusions: There were no significant differences in efficacy between the two treatment groups. The incidence of SATs was slightly higher on M-CAVI. [Table: see text]

Phase II Trial of Cisplatin, Gemcitabine, and Bevacizumab As First-Line Therapy for Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU 04-75

2011 ◽  
Vol 29 (12) ◽  
pp. 1525-1530 ◽  
Author(s):  
Noah M. Hahn ◽  
Walter M. Stadler ◽  
Robin T. Zon ◽  
David Waterhouse ◽  
Joel Picus ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
First Line ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

PurposeNovel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC.Patients and MethodsChemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2on day 1, gemcitabine 1,000 to 1,250 mg/m2on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days.ResultsForty-three patients with performance status of 0 (n = 26) or 1 (n = 17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progression-free survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met.ConclusionCGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

A randomized phase II study of sequential carboplatin/paclitaxel (CP) and gefitinib (G) in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC): Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7096-7096 ◽  
Author(s):  
H. Nokihara ◽  
Y. Ohe ◽  
M. Kawaishi ◽  
T. Kato ◽  
N. Yamamoto ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Performance Status ◽  
Survival Rates ◽  
Phase Iii ◽  
Optimal Timing ◽  
Pilot Studies ◽  
Randomized Phase Ii

7096 Background: G has been shown to exhibit antitumor activity against NSCLC, however, the optimal timing of its administration remains unclear. We conducted a randomized phase II study of CP followed by G or G followed by CP in chemotherapy-naïve advanced NSCLC patients in order to select the candidate arm for a subsequent phase III study. Methods: Chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged between 20 to74 years, performance status 0–1, were randomized to either Arm A (carboplatin (AUC 6, day 1) plus paclitaxel (200 mg/m2, day 1) every 3 weeks for 4 courses followed by daily G (250 mg/day)) or Arm B (daily G until disease progression followed by CP every 3 weeks for 4 courses). The primary endpoint was overall survival, and the planned sample size for this randomized phase II study was 96 patients (Liu’s selection design for pilot studies on survival). Results: From June 2003 to October 2005, 97 patients were enrolled, and 96 of these patients were treated in this study. Forty-nine patients (males/females: 28/21, median age: 63 years, adeno/non-adeno: 43/6, stageIII/IV: 11/38, smoker/non-smoker: 27/22) were randomized to Arm A and 48 patients (males/females: 28/20, median age: 61 years, adeno/non-adeno: 42/6, stageIII/IV: 11/37, smoker/non-smoker: 28/20) to Arm B. The response rate to CP in Arm A was 32.7% (16/49), and that to G in Arm B was 29.8% (14/47). The median survival was not yet reached, and the 1-year survival rates were 64.5% and 70.5% in Arm A and arm B, respectively. As of January 2006, one patient had died of treatment-related perforative peritonitis and two patients had developed interstitial lung disease. Conclusions: G exhibits similar antitumor activity to CP in chemotherapy-naïve patients with advanced NSCLC. The preliminary survival analysis is proposed to be conducted in April 2006. No significant financial relationships to disclose.

Quadruplet regimen with capecitabine, irinotecan, oxaliplatin, and bevacizumab in chemo-naive patients with metastatic colorectal cancer: Results from the safety lead-in of QUATTRO-II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 57-57
Author(s):  
Hideaki Bando ◽  
Daisuke Kotani ◽  
Masahito Kotaka ◽  
Akihito Kawazoe ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Braf V600e ◽  
Phase Iii ◽  
Fixed Dose ◽  
Wild Type ◽  
Randomized Phase Ii ◽  
Level 1 ◽  
Grade 3

57 Background: FOLFOXIRI plus bevacizumab (BEV) is regarded as the standard of care for selected patients (pts) with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea. The AXEPT phase III study showed that the modified capecitabine (CAP) + irinotecan (IRI) + BEV (CAPIRI+BEV) [CAP 1600 mg/m2, IRI 200 mg/m2, and BEV 7.5 mg/kg q3wk] treatment was non-inferior to FOLFIRI+BEV, with a lower incidence of hematologic toxicity. We hypothesized that the modified CAPIRI combined with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) would be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: The QUATTRO-II study is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses (RD) of OX and IRI were investigated as a safety lead-in. In Step 2, pts are randomized to either the RD of CAPOXIRI+BEV or FOLFOXIRI+BEV. In Step 1, four dose levels of CAPOXIRI (fixed dose of CAP 1600 mg/m2 and BEV 7.5 mg/kg plus escalated or de-escalated doses of OX and IRI, q3wk) were investigated in a 3+3 manner. A dose level of ≤ 2/6 of dose-limiting toxicity (DLT) cases was expected as the RD. Results: A total of 9 pts (3 at Level 0, 6 at Level 1) were included in Step 1. The baseline characteristics were as follows: the median age was 62 years; 6 were male; 6 presented with a left-sided tumor; 8 had a performance status of 0; all wild type/ RAS mutant/ BRAF V600E mutant were 8/1/0; and UGT1A1 wild type/*6 single hetero/*28 single hetero were 7/0/2. In Level 0 (IRI 200 mg/m2, OX 100 mg/m2), one grade 4 neutropenia and one grade 3 anorexia were observed, but without DLT. In Level 1 (IRI 200 mg/m2, OX 130 mg/m2), two grade 4 neutropenia and one grade 3 colitis were observed, with 1 DLT (febrile neutropenia) case, fully recovered without G-CSF administration. No treatment-related deaths were observed. Although dose modifications were needed in 4 of the 6 pts, no further safety concerns related to treatment continuity were observed in the 2nd or subsequent cycles. Thus, we determined that the dose administered in Level 1 is the RD for Step 2. According to the preliminary efficacy results at 8 weeks after initiating study treatment, 6 pts achieved a partial response (2 in Level 0 and 4 in Level 1). Conclusions: The RD of CAPOXIRI+BEV was 200 mg/m2 IRI, 130 mg/m2 OX, 1600 mg/m2 CAP, and 7.5mg/kg BEV. The randomized phase II Step (Step 2) of QUATTRO-II is ongoing. Clinical trial information: NCT04097444.

scholarly journals Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

2020 ◽  
Vol 10 ◽  
Author(s):  
Pierre-Yves Cren ◽  
Loïc Lebellec ◽  
Thomas Ryckewaert ◽  
Nicolas Penel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Multikinase Inhibitors ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1337-1345 ◽  
Author(s):  
Eric Van Cutsem ◽  
Michael Findlay ◽  
Bruno Osterwalder ◽  
Walter Kocha ◽  
David Dalley ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Single Agent ◽  
Dose Intensity ◽  
Patient Characteristics ◽  
Complete Response ◽  
Phase Iii ◽  
Effective Treatment Option ◽  
Randomized Phase Ii

PURPOSE: To evaluate in patients with advanced colorectal cancer (CRC) three treatment regimens of oral capecitabine in order to select the most appropriate regimen for testing in phase III. PATIENTS AND METHODS: Three capecitabine schedules were evaluated in a randomized phase II design: arm A, 1,331 mg/m2/d bid continuously; arm B, 2,510 mg/m2/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 mg/m2/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). RESULTS: One hundred nine patients were randomized; 39 patients were assessable for efficacy in arm A, 34 in arm B, and 35 in arm C. Patient characteristics were balanced in the arms. Confirmed tumor responses (partial response [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patients with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with two CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, more toxicity was seen with capecitabine plus leucovorin, particularly diarrhea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity. CONCLUSION: Capecitabine offers a new, effective treatment option as an oral single agent in advanced CRC. Promising overall response rates were reported for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermittent single-agent capecitabine schedule is proposed for phase III evaluation, based on considerations of toxicity, dose-intensity, response rate, and TTP.

Phase II Window of Idarubicin in Children With Extraocular Retinoblastoma

1999 ◽  
Vol 17 (6) ◽  
pp. 1847-1847 ◽  
Author(s):  
Guillermo L. Chantada ◽  
Adriana Fandiño ◽  
Gabriel Mato ◽  
Sandra Casak
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Progressive Disease ◽  
Bone Marrow Involvement ◽  
Complete Response ◽  
Phase Iii ◽  
Starting Dose ◽  
Hematopoietic Toxicity ◽  
Grade 3 ◽  
Phase Iii Studies

PURPOSE: The aim of this study was to evaluate in an upfront phase II study the response to idarubicin in children with extraocular retinoblastoma. PATIENTS AND METHODS: The starting dose of idarubicin was 15 mg/m2/d (days 1 and 2) weeks 0 and 3. After an interim evaluation, the dose was reduced to 10 mg/m2/d (days 1 and 2) weeks 0 and 3 because of hematopoietic toxicity. Response was evaluated at week 6. RESULTS: At the Hospital JP Garrahan (Buenos Aires, Argentina), 10 patients (five bilateral) were entered onto the study from 1995 to 1998. A total of 19 cycles were administered. Extraocular sites included orbit (n = 10), bone marrow (n = 3), bone (n = 1), lymph node (n = 1), and CNS (n = 1). The response rate was 60% (95% confidence interval, 30% to 90%). One complete response was achieved, in addition to five partial responses, two cases of stable disease, and two cases of progressive disease. All patients with bone marrow involvement achieved complete clearance of tumor cells. The patient with CNS disease had progressive disease. All patients had severe hematopoietic toxicity (grade 4 neutropenia and grade 3/4 thrombocytopenia after most cycles). Other toxicities included grade 2 diarrhea in 30%. No echocardiographic changes were detected. CONCLUSION: Idarubicin is active in extraocular retinoblastoma. The activity of this drug should be explored in future phase III studies.

Phase II Study of Thalidomide in Escalating Doses for Follicular (F-NHL) and Small Lymphocytic Lymphoma (Sll): CALGB Study 50002.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3284-3284 ◽  
Author(s):  
David L. Grinblatt ◽  
Jeffrey Johnson ◽  
Donna Niedzwicki ◽  
David A. Rizzieri ◽  
Nancy Bartlett ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Phase Ii ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Complete Response ◽  
Lymph Node Biopsy ◽  
Prior Therapy ◽  
Median Daily Dose ◽  
Grade 3

Abstract Background: Thalidomide has marked activity in both untreated and heavily pretreated myeloma. Its activity in part is believed to be due to inhibition of bFGF and VEGF induced angiogenesis. Elevated levels of bFGF in serum and urine have correlated with decreased survival in lymphoma possibly through up-regulation of BCL-2. Methods: 25 patients (pts) with previously treated F-NHL and SLL were registered and treated on this multi-institutional study from July 2001–April 2004 to evaluate the efficacy and safety of oral thalidomide in this patient group. Pts had B-cell SLL (7: 36.8%), F-NHL grade 1 (7: 36.8%), grade 2 (3: 15.8%) and grade 3 (2: 10.1%) NHL. Pts were eligible for entry with up to 3 prior chemotherapy (CT) and 2 immunotherapy (IT) regimens provided performance status was ≥ 1. Pts with new onset of B-symptoms, rising LDH, rapid tumor growth or greater than one year from initial diagnosis were required to undergo repeat lymph node biopsy to exclude recent transformation. Pts with CNS involvement, prior peripheral neuropathy >gr 1, HIV+, and pregnant or nursing women were also excluded. Pts were required to have Cr <2 x ULN, AST/ALT <2.5 x ULN and an ANC > 750. Median age at study entry was 60 years (36–87). Prior therapy was evaluated in 20 pts and 17/20 had received multi-agent CT while 12/20 pts received prior IT. Thalidomide was initiated at a dose of 200 mg daily and escalated by 100 mg daily every 1–2 weeks as tolerated with a maximal dose of 800 mg/d. If ≥ gr 2 peripheral neuropathy or ≥ gr 3 somnolence or mood changes occurred, the dose was held for one week and restarted at 50% of the prior daily dosage. Results: The median daily dose was 400 mg (range 50–800 mg). There was 1 complete response (CRu-residual abnormality) in a pt with SLL and one partial response in a pt with F-NHL grade 1 (ORR 8%: 95%CI: 1–26%). 16 pts had progressive disease during therapy and 2 died of disease soon after stopping therapy due to adverse events. One patient continues on therapy without progression of disease to date. The remaining 4 pts were taken off of therapy prior to the first 3 month evaluation. The reason for withdrawal was pt refusal (2) and adverse events (2). The median event free survival was 2.6 months (95% CI:1.4–4.4 mos) with a median overall survival of 23.3 months. Toxicity information on 24/25 pts revealed 4 (17%) with grade 4 neutropenia with 1/4 febrile as well. The most common grade 3 toxicities were anemia (13%), dyspnea (13%), fatigue (8%) and neurologic toxicities consisting of somnolence, dizziness, depression and anxiety (21%). Peripheral sensory neuropathy was reported as gr 2 in 8% and gr 3 in 8%. However, 38% of pts were reported as experiencing gr 2 fatigue. There were no grade 5 toxicities. Conclusion: These phase II trial results in a pretreated pt population demonstrate that, despite an acceptable toxicity profile, thalidomide has only minimal efficacy in F- NHL and SLL.

Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naïve patients with metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
B. Escudier ◽  
C. Szczylik ◽  
T. Demkow ◽  
M. Staehler ◽  
F. Rolland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Prognostic Score ◽  
Primary Objective ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

4501 Background: Sorafenib, an oral multi-kinase inhibitor that targets tumor growth and vascularization, significantly prolonged PFS in a Phase III trial with previously treated mRCC patients. This randomized Phase II trial investigated the efficacy and tolerability of sorafenib compared with IFN in first-line therapy of patients with clear-cell RCC. Methods: Untreated patients with mRCC were stratified by MSKCC prognostic score and randomized to receive continuous oral sorafenib 400 mg bid or IFN 9 million units tiw, with an option of dose escalation (600 mg bid sorafenib) or crossover from IFN to sorafenib upon disease progression. The study assessed PFS at 99 events as primary objective, best response (RECIST), overall survival, health-related quality of life, and adverse events (AEs). Results: Baseline characteristics of 188 patients (sorafenib n=97; IFN n = 91) were: median age 62.0 years; MSKCC score: 57% low, 41% intermediate, 1% high; prior nephrectomy: 82%; ECOG 0:1, 55.3%:44.7%. As of January 6, 2006, PFS events have been reported for 64 (34%) patients. Preliminary data showed drug-related AEs of any severity (sorafenib vs IFN) in 50.5% vs 51.6% of patients (≥grade 3: 8.2% vs 11.0%), including diarrhea (24.7% vs 5.5%), fatigue (14.4% vs 20.9%), fever (2.1% vs 18.7%), hypertension (13.4% vs 0%), nausea (5.2% vs 13.2%), flu-like syndrome (1.0% vs 6.6%), hand-foot skin reaction (6.2% vs 0%), and rash/desquamation (4.1% vs 0%). Drug-related metabolic/laboratory abnormalities at grade 3 (no grade 4) comprised hypophosphatemia (21.7% vs. 0%), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%) and hypoalbuminemia (0% vs. 3.6%). Five patients receiving IFN withdrew from treatment due to AEs, whereas only one patient withdrew from sorafenib. Conclusions: Sorafenib was generally well tolerated in RCC patients in the first-line setting, with relatively infrequent drug-related AEs ≥grade 3. Full PFS data will be presented at the meeting. [Table: see text]

Efficacy and toxicity of two schedules of R-CHOP plus bortezomib in front-line B lymphoma patients: A randomized phase II trial from the Groupe d’Etude des Lymphomes de l’Adulte (GELA)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8010-8010 ◽  
Author(s):  
N. Mounier ◽  
V. Ribrag ◽  
C. Haioun ◽  
G. Salles ◽  
J. Golfier ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Hematologic Malignancies ◽  
Front Line ◽  
Cardiac Events ◽  
Serious Adverse Events ◽  
B Lymphoma ◽  
Randomized Phase Ii ◽  
Histological Transformation ◽  
Grade 3

8010 Background: Bortezomib is the first proteasome inhibitor that showed promising activity in hematologic malignancies. In Jan 2005, we initiated a phase II randomized trial to evaluate front-line R-CHOP + bortezomib in B lymphoma pts. Methods: 6 cycles of standard R-CHOP (d1=d21) were planned, pts were randomized between 2 schedules of bortezomib: arm A (d 1,4,8,11), arm B (d 1,8). For the first 24 pts (step1), bortezomib was administred at 1 mg/m2 in arm A and 1.3 mg/m2 in arm B. For the next 24 pts (step2), it was increased at 1.3 mg/m2 and 1.6 mg/m2 respectively. G-CSF and EPO supports were allowed. Primary endpoint was CR rate after 6 cycles. Results: The trial was closed in Apr 2006 after inclusion of 49 pts. Sex ratio M/F was 28 /21. Median age: 63 years [32–76]. Pathology: 4 Lymphoplasmocytic, 4 small lymphocyte, 8 MZL, 2 Malt, 11 FL , 7 FL with histological transformation, 4 Mantle cell and 9 DLBC without adverse factor. Performance status 2–4: 4 pts; stage 4: 33 pts; LDH>N: 16 pts and IPI 2–3: 18 pts. According to triangular-test interim analysis (Jan 2006), arm A was closed at 20 pts (11 step1, 9 step2). 29 pts received arm B (10 step1, 19 step2). 290 cycles of R- CHOP and 819 injections of bortezomid were given. In arm A, 5/20 pts received less than 90% of scheduled dose of bortezomib (all in step2); in arm B, 7/29 pts (2 step1 and 5 step2). Grade 3–4 thrombopenia occurred in 14% of cycles (35% arm A, 0% arm B, 14% step2), Grade 3–4 leucopenia in 41 % (35% arm A, 45% arm B, 43% step2). Neurological toxicity occurred in 21 pts: grade 2 in 11 (1 arm A, 10 arm B, 9 in step2) and grade 3–4 in 10 (5 arm A, 5 arm B, 9 in step 2). 6 of them were considered as serious adverse events. Other grade 3–4 toxicities were 1 constipation (1 arm B, step2), 3 infections (2 arm A, 1 arm B, 2 step 2) and 2 cardiac events (1 arm A, 1 arm B). 48 pts were evaluable for response: 40 achieved CR/CRU: 18/20 in arm A, 22/28 in arm B. There were 5 PR (1 arm A, 4 arm B), 1 SD (arm A) and 2 PD (arm B). 19/21 pts achieved CR in step 1 and 21/27 in step 2. After 1 year median follow up, OS was 100% and EFS 80%. Conclusions: R- CHOP+Bortezomid is an effective regimen with 83% CR rate. However, the higher doses of bortezomib lead to severe neuropathy and suggest that association with vinca alcaloides should be avoided. No significant financial relationships to disclose.

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