Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 717-717 ◽  
Author(s):  
Barbara F. Eichhorst ◽  
Raymonde Busch ◽  
Clemens M. Wendtner ◽  
Michael Hallek ◽  
Keyword(s):  
Age Groups ◽  
The Elderly ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Binet Stage ◽  
Grade 3

Abstract Introduction: F based regimen have become the standard treatment in CLL at least in younger pts. However, in elderly pts chlorambucil is still frequently used since it is easy to administer and has less side effects. Here we compare the efficacy and toxicity of F administered to younger pts and elderly pts treated between 1999 and 2004 within two phase III trials of GCLLSG. Patients: 362 pts (median age 59 [range 37–65] years) were randomized to F (n=182) or F plus cyclophosphamide (n=180) within the CLL4 trial. 191 elderly pts (median age 71 [range 65–79] years) were treated with F (92 pts) or chlorambucil (99 pts) within the CLL5 protocol. Inclusion criteria were identical in both trials except for age limits. All pts were previously untreated and in advanced stage Binet C or Binet B with symptoms which require therapy or Binet A with severe B-symptoms. In both studies the F regimen consisted of 30 mg/m2/day (d) IV for 5 consecutive days, every 28 d for up to 6 cycles. Anti-infective prophylaxis and growth factors were not given routinely in both trials. Results: Most of patients in both age groups were in Binet stage B (54% of the younger pts and 52% of the elderly), 35% in each age group were in Binet stage C, 11% and 13% respectively in Binet stage A. No significant difference in the main clinical features was observed except for a higher incidence of concomitant disease in the elderly (61% versus 36%, p=0.001). A mean number of 5.2 F courses was administered in the CLL4 trial and 4.9 courses in the CLL5 trial. The mean administered cumulative dose of F per pt was lower in the elderly pts (1076 mg vs. 1194 mg, p= 0.05). Overall response rates were similar in both arms, with 82.9% in the younger group and 85.7% in the elderly. The complete remission rate was 6.7% in the younger patients and 10.4% in the elderly (p= 0.3). After a follow up time of 24 months (mo) the progression-free survival (PFS) was significantly shorter in the elderly group with 18.7 mo compared to 19.8 mo in the younger group after 22 mo observation time (p=0.03). The overall survival (OS) was significantly impaired in elderly pts as well (29 mo versus median not reached, p<0.001). Progressive disease was the main cause of death in both age groups. In each group 3 treatment related deaths occurred due to infection or hemolysis. The incidence of side effects was similar in both age groups. Severe, CTC grade 3 and 4, myelosuppression occurred in 39% of the younger and 41% of the elderly pts. No difference in the rate of leukocytopenia, thrombocytopenia or anemia was oberved as well. The incidence rate and severity of infections was similar in both groups (24% vs. 32% all and 8.7% vs. 6.9% CTC grade 3 and 4). The incidence of second neoplasia was significantly higher in the elderly pts (2.2% vs. 12.2%, p=0.001). In comparison the prevalence rate of neoplasia in the U.S. population peaks at 11% in the age group of 70–79 (SEER cancer statistic review: 1972–2002). Conclusion: F is a well tolerated treatment regimen in first line therapy of elderly pts with CLL. Response rates were similar in both age groups. PFS and OS were significantly shorter in the elderly population. The incidence of second neoplasia was significantly higher in the elderly pts, but is only slightly increased in comparison to the normal population.

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

Doxorubicin and Paclitaxel Versus Fluorouracil, Doxorubicin, and Cyclophosphamide as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomized Phase III Multicenter Trial

2001 ◽  
Vol 19 (6) ◽  
pp. 1707-1715 ◽  
Author(s):  
Jacek Jassem ◽  
Tadeusz Pieńkowski ◽  
Anna Płuzańska ◽  
Svetislav Jelic ◽  
Vera Gorbunova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Time To Progression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m2 followed 24 hours later by paclitaxel 220 mg/m2) or FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non–anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P = .032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P = .034]; overall survival 23.3 months v 18.3 months [P = .013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P < .001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Health related quality of life (HRQOL) evaluated with the EORTC C30 questionnaire in first line therapy of elderly patients with chronic lymphocytic leukemia (CLL): Results of a phase III trial of the German CLL Study Group (GCLLSG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7572-7572 ◽  
Author(s):  
B. F. Eichhorst ◽  
R. Busch ◽  
M. Hallek
Keyword(s):  
Social Functioning ◽  
Age Groups ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Response To Treatment ◽  
First Line ◽  
Elderly Age ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

7572 Background: The GCLLSG evaluated the efficacy of fludarabine (F) versus (vs.) chlorambucil (Clb) in first line therapy of older patients with advanced CLL. HRQOL was evluated by using the EORTC C30 questionnaire. Methods: Pts were randomized to receive 6 courses of F (25 mg/m²/day (d) IV for 5d; 92 pts) or 12 months (mo) of Clb (0.4–0.8 mg/kg/d PO, every 15d; 99 pts). All pts were previously untreated, aged between 65 and 79 years and in advanced stage Binet C or symptomatic Binet B or A. Primary endpoints were overall survival (OS) and progression free survival (PFS), secondary endpoint was HRQOL. The EORTC C30 questionnaire (version 2.0) was sent to all patients at baseline and after 6, 12 and 24 mo. Scores (0–100) for 15 different measures (1 global HRQOL, 5 functional, 3 symptom and 6 single item scales) were evaluated at each time point. Results: F induced significantly higher response rates and prolonged the PFS, while no significant difference in OS was observed. At baseline 130 of 191 pts (68%) completed the questionnaires followed by more than 80% at mo 6 to 24. Compliance rates were similar in both treatment arms. Between pts completing questionnaires or not no statistically significant differences in perfomance status, age, stage or response to treatment were observed. HRQOL differences in comparison to baseline values were significantly improved after F treatment in global HRQOL, role and social functioning after 12 months as shown by the table. Responders had a significantly better global HRQOL and social functioning as well. Except for an impaired physical functioning no differences in HRQOL were observed between different age groups (65–69, 70–74, 75–79). Conclusion: Elderly F treated patients with CLL showed improvement inglobal HRQOL. Elderly age groups had a similar HRQOL as younger age groups. [Table: see text] [Table: see text]

Irinotecan/5-FU/FA (I-FU) or 5-FU/FA (FU) first-line therapy in older and younger patients with metastatic colorectal cancer: Combined analysis of 2,691 patients in randomized controlled trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4071-4071 ◽  
Author(s):  
G. Folprecht ◽  
M. T. Seymour ◽  
L. Saltz ◽  
J. Y. Douillard ◽  
R. J. Stephens ◽  
...  
Keyword(s):  
Phase Iii ◽  
First Line ◽  
Younger Patients ◽  
Randomized Controlled ◽  
First Line Therapy ◽  
Line Therapy ◽  
Source Data ◽  
Phase Iii Trials ◽  
Receive Treatment ◽  
Ecog Ps

4071 Background: Irinotecan containing first line therapy has been shown to improve efficacy in first line therapy. Pooled analyses demonstrated that elderly patients benefit in a similar way as younger patients if 5-FU or 5-FU/oxaliplatin is administered as palliative or adjuvant treatment within clinical trials (Sargent, NEJM 2001, Folprecht, Ann Oncol 2004, Goldberg JCO 2006). Methods: We present an updated metaanalysis using source data of randomized trials (Saltz 2000, Douillard 2000, Köhne 2005 [EORTC 40986] and Seymour 2005 [FOCUS]) and compared the efficacy and toxicity in older (=70 years) and younger (<70 years) patients receiving first line 5- FU/FA with or without irinotecan. Randomized patients who did not receive treatment were excluded. Results: A total of 2,691 pts. was enrolled into the analysis ( table 1 ). There was no imbalance regarding risk factors (ECOG PS, WBC, No. of tumor sites, alkal. phosphatase, LDH) between elderly and younger patients. Older and younger patients had significantly improved response rates and PFS with I-FU compared to FU. Younger patients had significantly longer OS with I-FU, older patients a trend to longer OS with I-FU ( table 1 ). I- FU was associated with more grade >= 3 toxicity in the general population, but there were no significant differences regarding toxicity between older and younger patients ( table 1 ). Conclusion: Patients over 70 yrs who are selected for inclusion in phase III trials derive similar benefits from irinotecan-containing chemotherapy, and with similar risks of toxicity, compared with younger patients. [Table: see text] [Table: see text]

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 2006-2012 ◽  
Author(s):  
Jim Cassidy ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Safety and efficacy analysis by histology of weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7592-7592 ◽  
Author(s):  
Markus Frederic Renschler ◽  
Isamu Okamoto ◽  
Jeremy K. Hon ◽  
Vera Hirsh ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Iii ◽  
Positive Trend ◽  
First Line ◽  
Phase Iii Trial ◽  
Efficacy Analysis ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
And Gender

7592 Background: Treatment of advanced NSCLC differs by histology, with fewer options and poorer outcomes in pts with squamous histology. In a phase III trial of nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) vs solvent-based paclitaxel (sb-P) + C, the primary endpoint of ORR was significantly improved from 25% to 33%, p = 0.005, with a 1-month improvement in OS (p = NS) and improved safety. This analysis evaluated efficacy and safety by histology. Methods: Pts with untreated stage IIIB/IV NSCLC were randomized 1:1 (stratified by age, histology, region, stage, and gender) to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day 1 q 21 days. ORR and PFS were determined by blinded centralized review. Results: In squamous pts, nab-P/C produced a significantly higher ORR (41% vs 24%, p < 0.001), similar PFS (5.6 vs 5.7 mo, HR: 0.865) and >1-month improvement in OS (10.7 vs 9.5 mo, HR: 0.890) vs sb-P/C (Table). nab-P/C was as effective as sb-P/C in nonsquamous pts for ORR (26% vs 25%, p = 0.808), PFS (6.9 vs 6.5 mo, HR: 0.933), and OS (13.1 vs 13.0 mo, HR: 0.950). In both squamous and nonsquamous pts, nab-P/C vs sb-P/C produced lower rates of grade 3/4 neuropathy (3% vs 11% and 3% vs 12%, respectively, p < 0.001 both), neutropenia (43% vs 51%, p = NS, and 50% vs 63%, p = 0.008), and higher but manageable rates of anemia (27% vs 4% and 28% vs 9%, p < 0.001 both) and thrombocytopenia (21% vs 7% and 16% vs 11%, p < 0.001 both). Conclusions: In pts with advanced NSCLC, nab-P/C demonstrated a favorable risk-benefit profile as a first-line therapy regardless of histology. Significantly improved ORR and a positive trend in OS were observed in pts with squamous histology. [Table: see text]

Prescribing preferences (PPrefs) of U.S.-based medical oncologists (MOs) for choice of therapy after failure of first-line FOLFOX plus bevacizumab (FFB) in patients with metastatic colorectal cancer (MCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 533-533
Author(s):  
Johanna C. Bendell ◽  
Susan L. Britton ◽  
Maria Lankford ◽  
Arden Buettner ◽  
Mark R. Green ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Real Life ◽  
Phase Iii ◽  
Audience Response ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response ◽  
Phase Iii Trials

533 Background: Phase III trials have tested biologic (bio) agents (bevacizumab [bev], anti-EGFR antibodies, ziv aflibercept [ziv]) plus chemotherapy (CT) vs. CT alone after failure of first-line therapy in patients given CT + bev first line. Several have shown improvements in progression-free and overall survival (OS) with the CT + bio approach, but it is not clear how these therapies are being used in the “real life” setting. Methods: Since 3/2013 PPrefs for this setting among 276 MOs were studied using a validated, proprietary, live, case-based market research tool. A core scenario and variations based on KRAS status and first-line therapy outcome were tested (S1, S2, S3, S4). PPref data acquired using blinded audience response technology. All sources of research support were blinded. Core scenario: 49 yr old female with cecal mass, liver/lung metastases, confirmed wt KRAS for S1-3, given FFB first line. S1: FFB x 16 wks → excellent PR → 5FU bev X 16 wks → progressive disease [PD]; S2: FFB x 16 wks → excellent PR → bev alone x 16 wks → PD; S3: FFB → stable disease [SD] x 5 months as best response [BR] → PD; 4) Here changed to mutKRAS; FFB x 8 wks → PD as BR. Results: Findings shown below (Table). Conclusions: In scenarios with wt KRAS, first-line response to FFB, a majority plan bev again second line. If BR to FFB is SD in WT KRAS, anti-EGFR antibody-based therapy is used more often. In S 1-3, ziv is the PPref of 7 - 14% of MOs studied. With mutKRAS and PD as BR to FFB, use of an antiangiogenic + second-line CT is preferred by > 80%, nearly equally split between bev and ziv. Recent phase III trial data showing OS benefits are reflected in current MOs first failure PPrefs. [Table: see text]

Retrospective, cohort study evaluating empiric dose-reduced nab-paclitaxel with gemcitabine in metastatic pancreatic adenocarcinoma: A single institution experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 456-456
Author(s):  
Olugbenga Olanrele Olowokure ◽  
LeeAnn Geraghty ◽  
Lisa Grate ◽  
Alicia Gesenhues ◽  
Adam Lane ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pancreatic Adenocarcinoma ◽  
Primary Outcome ◽  
Phase Iii ◽  
Single Institution ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

456 Background: The phase III MPACT trial was conducted to assess OS in patients with metastatic pancreatic adenocarcinoma (mPAC) receiving nab-paclitaxel (nab-P) 125 mg/m2 + gemcitabine (G) 1000 mg/m2 on days 1, 8, and 15 every 28 days. Due to reported increased incidence of adverse events (AEs) at this dose, practice at UC Health outside the setting of a clinical trial is to empirically dose reduce (EDR) nab-P to 100 mg/m2. This study is a review of the efficacy of EDR nab-P + G in patients with mPAC compared to MPACT data. Methods: This retrospective, single-center, cohort study included patients ≥18 years of age with mPAC (by biopsy) receiving first line therapy with EDR nab-P + G from January 1, 2012 to March 31, 2017. Primary outcome is OS. Secondary outcomes include PFS, CA19-9 percent reduction, incidence of grade ≥ 3 AEs. Results: See table. Conclusions: In patients with mPAC, EDR nab-P plus G demonstrated a median OS of 10 months and PFS of 5 months. 53% of patients had a 20% CA19-9 reduction from baseline with a 1 year OS rate of 45%. The incidence of grade ≥ 3 AEs appeared to be acceptable. [Table: see text]

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