A Randomized Trial Comparing Defined-Duration With Continuous Irinotecan Until Disease Progression in Fluoropyrimidine and Thymidylate Synthase Inhibitor—Resistant Advanced Colorectal Cancer

2004 ◽  
Vol 22 (15) ◽  
pp. 3023-3031 ◽  
Author(s):  
Rohit Lal ◽  
James Dickson ◽  
David Cunningham ◽  
Ian Chau ◽  
Andrew R. Norman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Disease Progression ◽  
Advanced Colorectal Cancer ◽  
Phase Iii ◽  
Random Assignment ◽  
Duration Of Disease ◽  
Grade 3 ◽  
Synthase Inhibitor

Purpose Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment. Patients and Methods Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38). Results From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment. Conclusion For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.

Phase III Comparison of Two Irinotecan Dosing Regimens in Second-Line Therapy of Metastatic Colorectal Cancer

2003 ◽  
Vol 21 (5) ◽  
pp. 807-814 ◽  
Author(s):  
Charles S. Fuchs ◽  
Melvin R. Moore ◽  
Graydon Harker ◽  
Luis Villa ◽  
David Rinaldi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Significant Difference ◽  
Global Quality Of Life ◽  
Grade 3

Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients. Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m2) or once every 3 weeks (350 mg/m2, or 300 mg/m2 in patients who were ≥ 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation). Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively; P = .43), or median time to progression (4.0 v 3.0 months, respectively; P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups. Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.

scholarly journals Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer

2009 ◽  
Vol 102 (1) ◽  
pp. 59-67 ◽  
Author(s):  
T Conroy ◽  
M Hebbar ◽  
J Bennouna ◽  
M Ducreux ◽  
M Ychou ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
Phase Iii Study

Health related quality of life in older or frail patients with advanced colorectal cancer treated with dose reduced capecitabine

2018 ◽  
Vol 9 (6) ◽  
pp. 659-664 ◽  
Author(s):  
Daniel Breadner ◽  
Mark David Vincent ◽  
Derek Jonker ◽  
Christine Cripps ◽  
Paul Klimo ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Health Related Quality ◽  
Frail Patients ◽  
Related Quality ◽  
Health Related

Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 266-266
Author(s):  
Andrew X. Zhu ◽  
Teresa Macarulla ◽  
Milind M. Javle ◽  
Robin Kate Kelley ◽  
Sam Joseph Lubner ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Endpoint ◽  
Failure Time ◽  
Objective Response ◽  
Idh1 Mutation ◽  
High Rate ◽  
Phase Iii ◽  
Double Blind Study ◽  
Grade 3

266 Background: CCA is a rare cancer for which there are limited effective therapies. IDH1 mutations occur in ~20% of intrahepatic CCAs, resulting in production of the oncometabolite D-2-hydroxyglutarate, which promotes oncogenesis. IVO (AG-120) is a first-in-class, oral, small-molecule inhibitor of mutant IDH1 (m IDH1). ClarIDHy aimed to demonstrate the efficacy of IVO vs PBO in pts with unresectable or metastatic m IDH1 CCA. The primary endpoint was met with significant improvement in progression-free survival (PFS) by independent radiology center (IRC) with IVO vs PBO (hazard ratio [HR] = 0.37, p < 0.0001). Objective response rate (ORR) and stable disease for IVO were 2.4% (3 partial responses) and 50.8% (n = 63) vs 0% and 27.9% (n = 17) for PBO. IVO pts experienced significantly less decline in physical and emotional functioning domains of quality of life at cycle 2 day 1 vs PBO pts (nominal p < 0.05). Methods: Pts with m IDH1 CCA were randomized 2:1 to IVO (500 mg PO QD) or matched PBO and stratified by prior systemic therapies (1 or 2). Key eligibility: unresectable or metastatic m IDH1 CCA based on central testing; ECOG PS 0–1; measurable disease (RECIST v1.1). Crossover from PBO to IVO was permitted at radiographic progression. Primary endpoint: PFS by IRC. Secondary endpoints included overall survival (OS; by intent-to-treat), ORR, PFS (by investigator), safety, and quality of life. The planned crossover-adjusted OS was derived using the rank-preserving structural failure time (RPSFT) model. Results: As of 31 May 2020, ~780 pts were prescreened for an IDH1 mutation and 187 were randomized to IVO (n = 126) or PBO (n = 61); 13 remain on IVO. Median age 62 y; M/F 68/119; 91% intrahepatic CCA; 93% metastatic disease; 47% had 2 prior therapies. 70% of PBO pts crossed over to IVO. OS data were mature, with 79% OS events in IVO arm and 82% in PBO. Median OS (mOS) was 10.3 months for IVO and 7.5 months for PBO (HR = 0.79; 95% CI 0.56–1.12; one-sided p = 0.093). The RPSFT-adjusted mOS was 5.1 months for PBO (HR = 0.49; 95% CI 0.34–0.70; p < 0.0001). Common all-grade treatment emergent adverse events (TEAEs, ≥ 15%) in the IVO arm: nausea 41%, diarrhea 35%, fatigue 31%, cough 25%, abdominal pain 24%, decreased appetite 24%, ascites 23%, vomiting 23%, anemia 18%, and constipation 15%. Grade ≥ 3 TEAEs were reported in 50% of IVO pts vs 37% of PBO pts, with grade ≥ 3 treatment-related AEs in 7% of IVO pts vs 0% in PBO. 7% of IVO pts experienced an AE leading to treatment discontinuation vs 9% of PBO pts. There were no treatment-related deaths. Conclusions: IVO was well tolerated and resulted in a favorable OS trend vs PBO despite a high rate of crossover. These data – coupled with statistical improvement in PFS, supportive quality of life data, and favorable safety profile – demonstrate the clinical benefit of IVO in advanced m IDH1 CCA. Clinical trial information: NCT02989857.

Impact of protracted venous infusion fluorouracil with or without interferon alfa-2b on tumor response, survival, and quality of life in advanced colorectal cancer.

1995 ◽  
Vol 13 (9) ◽  
pp. 2317-2323 ◽  
Author(s):  
M Hill ◽  
A Norman ◽  
D Cunningham ◽  
M Findlay ◽  
M Watson ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Symptomatic Improvement ◽  
Interferon Alfa ◽  
Life Questionnaire ◽  
European Organization ◽  
Significant Difference ◽  
Venous Infusion

PURPOSE The aim of this study was to investigate the effects of adding interferon alfa-2b (IFN) to protracted venous infusion fluorouracil (PVI 5-FU) from the start of treatment in patients with advanced colorectal cancer. PATIENTS AND METHODS Patients who attended our unit with histologically confirmed advanced colorectal cancer were randomized to receive either PVI 5-FU 300 mg/m2/d via Hickman line, and IFN 5 MU subcutaneously three times weekly, or PVI 5-FU alone. Treatment was given for a maximum of two 10-week blocks, with a 2-week gap for reassessment of all parameters. Quality of life (QL) was measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) pretreatment and every 6 weeks thereafter. RESULTS A total of 160 patients were randomized, with 155 eligible for assessment. Radiologic response was observed in 43 patients (28%): 17 of 77 (22%) in the 5-FU-plus-IFN arm (all partial responses [PRs]) and 26 of 78 (33%) in the 5-FU-alone group (complete responses [CRs] and 22 PRs) (difference not significant). Symptomatic improvement occurred in the majority of patients, and equally in both arms: 61% to 80% depending on the symptom. There was no significant difference between the two groups in failure-free survival (median, 161 v 193 days) or overall survival (median, 328 v 357 days). However, patients who received IFN did experience significantly more toxicity in the form of leukopenia (P = .001), neutropenia (P = .04), mucositis (P = .008), and alopecia (P = .0002). There were no toxic deaths and few notable differences in QL between the two arms. CONCLUSION This study confirms that PVI 5-FU is effective in treating the symptoms associated with metastatic colorectal carcinoma, with only mild to moderate toxicity and maintenance of QL. IFN 5 MU three times weekly does not enhance these palliative benefits.

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