Low-Dose Decitabine Versus Best Supportive Care in Elderly Patients With Intermediate- or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

2011 ◽  
Vol 29 (15) ◽  
pp. 1987-1996 ◽  
Author(s):  
Michael Lübbert ◽  
Stefan Suciu ◽  
Liliana Baila ◽  
Björn Hans Rüter ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Supportive Care ◽  
Low Dose ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Patient Reported ◽  
Grade 3

Purpose To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. Patients and Methods Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS). Decitabine (15 mg/m2) was given intravenously over 4 hours three times a day for 3 days in 6-week cycles. Results OS prolongation with decitabine versus BSC was not statistically significant (median OS, 10.1 v 8.5 months, respectively; hazard ratio [HR], 0.88; 95% CI, 0.66 to 1.17; two-sided, log-rank P = .38). Progression-free survival (PFS), but not acute myeloid leukemia (AML) –free survival (AMLFS), was significantly prolonged with decitabine versus BSC (median PFS, 6.6 v 3.0 months, respectively; HR, 0.68; 95% CI, 0.52 to 0.88; P = .004; median AMLFS, 8.8 v 6.1 months, respectively; HR, 0.85; 95% CI, 0.64 to 1.12; P = .24). AML transformation was significantly (P = .036) reduced at 1 year (from 33% with BSC to 22% with decitabine). Multivariate analyses indicated that patients with short MDS duration had worse outcomes. Best responses with decitabine versus BSC, respectively, were as follows: complete response (13% v 0%), partial response (6% v 0%), hematologic improvement (15% v 2%), stable disease (14% v 22%), progressive disease (29% v 68%), hypoplasia (14% v 0%), and inevaluable (8% v 8%). Grade 3 to 4 febrile neutropenia occurred in 25% of patients on decitabine versus 7% of patients on BSC; grade 3 to 4 infections occurred in 57% and 52% of patients on decitabine and BSC, respectively. Decitabine treatment was associated with improvements in patient-reported quality-of-life (QOL) parameters. Conclusion Decitabine administered in 6-week cycles is active in older patients with higher-risk MDS, resulting in improvements of OS and AMLFS (nonsignificant), of PFS and AML transformation (significant), and of QOL. Short MDS duration was an independent adverse prognosticator.

Low Dose Decitabine Versus Best Supportive Care in Elderly Patients with Intermediate or High Risk MDS Not Eligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study (06011) of the EORTC Leukemia and German MDS Study Groups

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 226-226 ◽  
Author(s):  
Pierre WijerMans ◽  
Stefan Suciu ◽  
Liliana Baila ◽  
Uwe Platzbecker ◽  
Aristoteles Giagounidis ◽  
...  
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Disease Progression ◽  
Low Dose ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Phase Iii Study ◽  
The Difference ◽  
Grade 3

Abstract Introduction: In 2002 the EORTC and the German MDS Study Group initiated a randomized phase III study comparing low dose Decitabine to supportive care in patients (pts) of 60 years or older with primary or secondary MDS or CMML. MDS patients with either 11–20% BM blasts or ≤ 10% blasts and poor cytogenetics could be included. Pts with a BM blast count between 21–30% without signs of disease progression for at least one month were also candidates for the study. Methods: Patients were centrally randomized; stratification factors were cytogenetics risk group, IPSS, MDS (primary vs secondary) and study centre, The treatment schedule was 15 mg/m2 Decitabine i.v. over 4 hours every 8 hours for the first 3 three consecutive days, of every 6 week-cycle, for a maximum of 8 cycles. Results were evaluated every 2nd cycle. When a complete remission was reached at least another 2 courses were given. The primary endpoint of the study was Overall Survival. AML free survival, Progression Free Survival (PFS), response rate, toxicity and QoL were secondary endpoints. A total of 185 deaths were required to detect a hazard ratio (HR) of 0.66 (alpha=5%, beta=20%). Intent-to-treat analysis was used. Results: Between 10.2002 and 5.2007 a total of 233 pts (149 male and 84 female) were recruited from 40 centres. The median age was 70 (60–90 years); RAEB-t was diagnosed in 32% of the pts. Most pts had an IPSS Intermediate-2 (55%) or high risk (38%). Poor risk cytogenetics was found in 46% of the patients. Prior therapy for MDS (not being intensive chemotherapy) was given in 20% of pts. The randomized groups were well balanced regarding stratification factors, age and FAB classification. The median follow up was 2.5 years. Time to Off Study was 180 (Decitabine) vs 112 days (SC arm). The median number of cycles given to the patients was 4 with 40%getting no more than 2 cycles. In a significant number of pts, subsequent treatment, consisting of transplant (10%) or induction chemotherapy (11%), was given. The distribution of best response in Decitabine vs SC arm was CR (13% vs 0%), PR (6% vs 0%), HI (15% vs 2%), SD (14% vs 22%), PD (29% vs 68%), hypoplasia (14% vs 0%), inevaluable (8% vs 8%). The 18 pts on Decitabine with a HI showed the following responses: 3-lineage (n=7), 2-lineage (n=5) and 1-lineage (n=6). The median time to response (CR/PR/HI) was 0.32 yrs and the response duration was 0.72 years. Median OS was 0.84 (Decitabine) vs 0.71 years (SC arm), estimated HR was 0.88, 95% CI 0.66–1.17, p=0.38 (logrank 2-sided). The PFS was significantly (p=0.004) longer in Decitabine vs SC arm: median was 0.55 vs 0.25 years, HR=0.68 (95% CI 0.52–0.88). Time to AML or Death was not significantly improved (p=0.24): median was 0.73 vs 0.51 years (HR=0.85, 95% CI 0.64–1.12). Toxicity. The toxicity was mainly cytopenia related toxicity that was either disease related or hematotoxicity; CTC grade 3–4 febrile neutropenia was 26% (Decitabine) vs 7% (SC arm) and Grade 3–4 infection was 59% vs 47%. Differences in non hematologic toxicities were mainly gastrointestinal: grade 1–2 nausea (28% vs 16%) and grade 1–2 vomiting (16% vs 9%). During the study period, 29 (Decitabine) vs 25 (SC arm) patients died: due to either progression to MDS/AML (7 vs 20), toxicity (9 vs 0), progression and/or toxicity (10 vs 1), other reasons (3 vs 4). Conclusions. Decitabine was found to be an effective drug in these high risk MDS patients with a overall RR of 34%, (similar to earlier studies), leading to a significant PFS improvement as compared to SC arm. The difference Decitabine vs SC arm regarding time to AML or Death was not significant. Due to shorter treatment duration (not being continued beyond 8 cycles) and maybe also due to subsequent treatments administered after disease progression, the difference regarding OS was lower (HR=0.88) and not statistically significant.

Phase II–III Study of Gemtuzumab Ozogamicin Monotherapy versus Best Supportive Care in Older Patients with Newly Diagnosed AML Unfit for Intensive Chemotherapy: First Results of the EORTC-GIMEMA AML-19 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 762-762 ◽  
Author(s):  
Sergio Amadori ◽  
Stefan Suciu ◽  
Dominik Selleslag ◽  
Giuliana Alimena ◽  
Liliana Baila ◽  
...  
Keyword(s):  
Supportive Care ◽  
Phase Ii ◽  
Older Patients ◽  
Phase Ii Study ◽  
Best Supportive Care ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Grade 3 ◽  
To Receive

Abstract Treatment of AML in the elderly remains challenging. In particular, few therapeutic options exist for patients (pts) who are not considered medically fit for intensive chemotherapy. Gemtuzumab ozogamicin (GO), a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, has demonstrated single agent efficacy in older patients with relapsed AML. In a previous trial we reported a complete response rate of 17% when the licensed dose/schedule of GO was used as frontline monotherapy for older unfit pts with AML, but excess hematologic and liver toxicity suggested changes in both dosing and scheduling to improve feasibility. The AML-19 study was designed as a sequential phase II–III trial in pts of age 61 or over with untreated AML, who could not be considered candidates for, or must have declined, conventional intensive chemotherapy. The primary objective of the phase II study was to investigate whether any of two different schedules of lower dose GO monotherapy (total delivered dose 9 mg/m2 in 2 or 3 fractions over one week) is sufficiently effective and tolerable frontline therapy to continue phase III comparison with best supportive care (BSC). Pts had to have adequate renal and hepatic function, and the WBC count had to be less than 30,000/cmm at the time of registration. Two-thirds of the pts were randomly assigned to receive a single induction course of either GO 3 mg/m2 iv on days 1, 3 and 5 (arm A), or GO 6 mg/m2 iv on day 1 and 3 mg/m2 on day 8 (arm B); the remaining third was assigned to the BSC arm. Randomization was stratified by age, performance status (PS), initial WBC, CD33 expression on marrow blasts, and Institution. Pts with no evidence of objective disease progression were eligible to receive continuation treatment with monthly outpatient infusions of GO at 2 mg/m2 for a maximum of 8 months. Primary end-point of the phase II study was clinical benefit rate (CBR) defined as the number of pts either achieving a remission (CR, CRp, PR) or maintaining a stable disease (SD) in each experimental arm. The arm associated with the highest CBR would be selected for phase III assessment, providing that it is at least 48% (Simon design). Between 06/2004 and 12/2006, 56 pts were randomized in the two experimental arms (arm A 29; arm B 27). The two arms were comparable in terms of age (arm A: median 77 yrs; arm B: median 78 yrs), PS >2 (arm A: 7%; arm B: 4%), secondary AML (arm A: 45%; arm B: 37%), and CD33 expression on ≥20% marrow blasts (arm A: 86%; arm B: 85%). In arm A, 6 pts achieved CR, 2 PR, and 3 maintained SD for an overall CBR of 38% (90% CI, 23%–55%); in arm B, 5 pts achieved CR, 1 CRp, and 11 maintained SD for an overall CBR of 63% (90% CI, 45%–78%). Most toxicities were <grade 3 in both arms and included nausea/vomiting, diarrhea, fatigue, stomatitis and transient elevations of serum transaminases and bilirubin. The rate of grade ≥3 infection was slightly higher in arm B (48% vs 31%), as was the incidence of severe bleeding (11% vs 0%). All-cause early mortality (<6 wks) occurred in 17% of pts in arm A (2 infection, 3 AML) and in 11% of pts in arm B (1 infection, 1 AML, 1 infection+AML). In summary, lower dose GO is a tolerable and active primary therapy for older AML pts who are considered unsuitable for intensive chemotherapy. The day 1+8 schedule (arm B) is associated with a more favourable efficacy profile, meeting the statistical criteria to be selected as the preferred regimen for phase III comparison with BSC. Accrual to the phase III trial is ongoing.

Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis.

2020 ◽  
Vol 38 (18_suppl) ◽  
pp. LBA1-LBA1 ◽  
Author(s):  
Thomas Powles ◽  
Se Hoon Park ◽  
Eric Voog ◽  
Claudia Caserta ◽  
B.P. Valderrama ◽  
...  
Keyword(s):  
Supportive Care ◽  
Stable Disease ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Primary Objective ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Grade 3

LBA1 Background: Platinum-based chemotherapy is an active 1L regimen for advanced UC; however, progression-free survival (PFS) and overall survival (OS) are generally short because of chemotherapy resistance. This randomized, phase 3 trial (JAVELIN Bladder 100; NCT02603432) evaluated avelumab (anti–PD-L1) as maintenance therapy following response or stable disease with 1L platinum-based chemotherapy in patients with advanced UC. Methods: Eligible patients with unresectable locally advanced or metastatic UC without disease progression after 4-6 cycles of gemcitabine with either cisplatin or carboplatin were randomized 1:1 to receive maintenance avelumab (10 mg/kg IV every 2 weeks) + best supportive care (BSC) or BSC alone, stratified by best response to 1L chemotherapy (complete/partial response vs stable disease) and by visceral vs nonvisceral disease when initiating 1L chemotherapy. The primary endpoint was OS, assessed from randomization in 2 primary populations: all randomized patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included PFS, objective response, and safety. Results: 700 patients were randomly assigned to maintenance avelumab + BSC (n=350) or BSC alone (n=350) and were followed for a median of 19.6 and 19.2 months, respectively. Overall, 358 (51%) had PD-L1+ tumors. Avelumab + BSC significantly prolonged OS vs BSC alone in all randomized patients (hazard ratio [HR] 0.69; 95% CI 0.56, 0.86; 1-sided p=0.0005); median OS with avelumab + BSC vs BSC alone was 21.4 vs 14.3 months, respectively. Avelumab + BSC also significantly prolonged OS vs BSC alone in patients with PD-L1+ tumors (HR 0.56; 95% CI 0.40, 0.79; 1-sided p=0.0003); median OS was not reached vs 17.1 months, respectively. An OS benefit was also observed across all prespecified subgroups. The HR for PFS based on blinded independent central review with avelumab + BSC vs BSC alone was 0.62 (95% CI 0.52, 0.75) in all randomized patients and 0.56 (95% CI 0.43, 0.73) in patients with PD-L1+ tumors. In treated patients in the avelumab + BSC (n=344) vs BSC alone (n=345) arms, respectively, all-causality adverse events (AEs) were reported at any grade in 98.0% vs 77.7% and at grade ≥3 in 47.4% vs 25.2%, and the most frequent grade ≥3 AEs were urinary tract infection (4.4% vs 2.6%), anemia (3.8% vs 2.9%), hematuria (1.7% vs 1.4%), fatigue (1.7% vs 0.6%), and back pain (1.2% vs 2.3%). Conclusions: JAVELIN Bladder 100 met its primary objective, demonstrating significantly prolonged OS with 1L maintenance avelumab + BSC vs BSC alone in advanced UC in all randomized patients and patients with PD-L1+ tumors. Efficacy benefits were seen across all prespecified subgroups, and the safety profile of avelumab was consistent with previous studies of monotherapy. Clinical trial information: NCT02603432 .

scholarly journals Bortezomib, Lenalidomide and Low-Dose Dexamethasone (VRD) Versus Lenalidomide and Low-Dose Dexamethasone (Ld) for Newly-Diagnosed Multiple Myeloma- a Randomized Phase III Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 906-906
Author(s):  
Anjali Mookerjee ◽  
Ritu Gupta ◽  
Shivali Jasrotia ◽  
Ranjit Sahoo ◽  
Rakesh Kumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3

Abstract Background: In this prospective study, we compared VRD with Ld as induction therapy for newly-diagnosed Multiple myeloma patients. The primary objective of this study is to compare the progression-free survival in the 2 arms. Methods: Between September 2014 and Oct 2016, 144 patients have been recruited and randomly assigned to receive 4 cycles of either Bortezomib 1.3 mg/m2 SC on days 1, 8, 15 and 22 with Lenalidomide 15mg/day from day 1 to 14 (Arm A) or Lenalidomide 25 mg/day from day 1 to 21 (Arm B). Patients in both arms received oral dexamethasone 40 mg on days 1,8,15 and 22. Both treatment regimens were 28-day cycles. All patients received 75 mg aspirin daily, acyclovir prophylaxis and monthly zoledronic acid. Response assessment was done at the end of the 4th cycle using the International Myeloma Working Group (IMWG) uniform response criteria. The study was approved by the Institute Ethics Committee (Ref IEC/NP-264/01-08-2014, RP-7/2014). Results: These are the results from an analysis of 143 patients (arm A-74, arm B-69). Baseline characteristics of patients were similar in both arms with respect to age, gender, ISS and DS stage, immunoglobulin subtype and serum LDH. Patients' median age is 56 years (range 31-70) in arm A and 52 years (range 28-69) in arm B. Gender M/F: Arm A 54/20 and 43/26 in arm B. ISS stage III 51 (68.9%) arm A vs 44 (63.8%) arm B. Serum LDH raised to &gt;250 u/L was observed in 25 (44.6%) vs 31 (52.5%) in arms A and B, p=0.4. Revised staging including ISS and serum LDH at baseline: stage III 47 (81%) and 37 (65%) in arms A and B respectively. 14 (18.9%) and 19 (27.5%) of patients had light chain myeloma in arms A and B respectively. Overall response rates (sCR+CR+VGPR+PR) is 78.4% vs 73.9% in arms A and B respectively, p=0.6; sCR + CR 21 (28.4%) and 21 (30.4%) respectively, p=0.86. Median follow-up 17.1 months (range 1 to 33). Median overall survival (OS) is 30.2 months (95% CI 28.2 to 32.2) and 28.6 months (95%CI 26 to 31.3) in arms A and B respectively, p=0.3. Median progression-free survival (PFS) was 27.8 months (95%CI 25.4 to 30.2) and 28 months (95%CI 24.6 to 31.4) respectively, p=0.3. Estimated one-year OS is 88% vs 85% in arms A and B, and PFS 83% vs 72%, respectively. Grade 3 anemia occurred in one patient in arm B, and grade 3 deep vein thromboses in one patient in arm A. One patient in arm A developed grade 4 myelosuppression leading to therapy change at the end of the first cycle. Conclusion: In this analysis - response rates and median progression-free survival are similar in both arms. Disclosures No relevant conflicts of interest to declare.

A phase III randomized, open label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8004-8004 ◽  
Author(s):  
Paul G. Richardson ◽  
Michel Attal ◽  
S. Vincent Rajkumar ◽  
Jesus San Miguel ◽  
Meral Beksac ◽  
...  
Keyword(s):  
Low Dose ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Free Survival ◽  
New Treatment ◽  
Grade 3

8004 Background: The primary objective of this phase 3 trial was to demonstrate progression free survival (PFS) improvement of isatuximab (Isa), a novel anti-CD38 monoclonal antibody, combined with pomalidomide (P)/dexamethasone (d) versus (vs) Pd. Methods: Patients (pts) with RRMM who received ≥2 prior lines, including lenalidomide (len) and a proteasome inhibitor (PI), refractory to last therapy were enrolled. IsaPd arm received Isa 10 mg/kg IV weekly for first 4 weeks (wks), then every 2 wks. Both arms received approved schedules of pom and dex (4mg PO days 1-21; 40mg [20mg if >75 yrs] PO or IV weekly) every 28 days until progression or unacceptable toxicity. Results: 307 pts (154 IsaPd, 153 Pd) were randomized and analyzed (ITT). Patient characteristics were well balanced across arms. Median age: 67 (36-86) yrs; median prior lines of therapy: 3 (2-11); estimated GFR: <60ml/min in 33.9% pts; 92.5% refractory to len, 75.9% to PI; and 19.5% pts had high-risk cytogenetics. At median follow-up of 11.6 months (mos), median PFS was 11.5 mos IsaPd vs 6.5 mos Pd; HR 0.596 (95% CI 0.44-0.81), P=0.001. PFS benefit was consistent across all major subgroups. ORR (≥PR) was 60.4% IsaPd vs 35.3% Pd, P<0.0001. VGPR rate or better was 31.8% IsaPd vs 8.5% Pd, and MRD negativity (NGS, 10-5) was seen in 5.2% IsaPd pts vs 0% Pd. At analysis date, overall survival (OS) was immature (99 events) but a trend to OS improvement in IsaPd (vs Pd) was observed (HR 0.687; 95% CI 0.461-1.023). Median treatment duration was 41 wks IsaPd vs 24 wks Pd; median Isa infusion (inf.) duration was 3.3h at 1st inf. and 2.8h at subsequent inf. Grade ≥3 AEs were observed in 86.8% IsaPd vs 70.5% Pd; 7.2% IsaPd and 12.8% Pd pts discontinued due to AEs; 7.9% IsaPd and 9.4% Pd pts died due to AEs. Inf. reactions were reported in 38.2% (2.6% grade 3-4) IsaPd. Grade ≥3 infections were seen in 42.8% IsaPd and 30.2% Pd, grade ≥3 neutropenia in 84.9% (febrile 11.8%) IsaPd and 70.1% (febrile 2.0%) Pd. Conclusions: IsaPd significantly improved PFS and ORR vs Pd, with a manageable safety profile. IsaPd is an important new treatment option for the management of RRMM. Clinical trial information: NCT02990338.

Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study

2020 ◽  
Vol 20 (11) ◽  
pp. 887-895 ◽  
Author(s):  
Martina Catalano ◽  
Giandomenico Roviello ◽  
Raffaele Conca ◽  
Alberto D’Angelo ◽  
Valeria Emma Palmieri ◽  
...  
Keyword(s):  
Performance Status ◽  
Real Life ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Grade 3 ◽  
Ecog Ps ◽  
Prognostic And Predictive Markers

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

scholarly journals THERAPEUTIC OPTIONS FOR PATIENTS WHO ARE NOT ELIGIBLE FOR INTENSIVE CHEMOTHERAPY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013050 ◽  
Author(s):  
Elihu Estey
Keyword(s):  
Life Expectancy ◽  
Supportive Care ◽  
Low Dose ◽  
Best Supportive Care ◽  
Therapeutic Options ◽  
Intensive Chemotherapy ◽  
Principal Problem

Although “less intense” therapies are finding more use in AML, the principal problem in AML remains lack of efficacy rather than toxicity. Hence less intense therapies are of little use if they are not more effective as well as less toxic than standard therapies.. Assignment of patients to less intense therapies should be based on other factors in addition to age. Azacitidine and decitabine, the most commonly used less intense therapies in AML very probably produce better OS than best “supportive care” or “low-dose” ara-C. However improvement is relatively small when compared to expected life expectancy in the absence of disease. Accordingly, while azacitidine or decitabine should be considered the standards against which newer therapies are compared, continued investigation of potentially more effective therapies needs to continue. Better means for evaluating the large number of these therapies (and their combinations) are also needed.   

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Secondary Resection ◽  
Phase Iii Study ◽  
Grade 3

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

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