Impact of age and medical comorbidity (MC) on adjuvant treatment outcomes for stage III colon cancer (CC): A pooled analysis of individual patient data from four randomized controlled trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3522-3522 ◽  
Author(s):  
Daniel G. Haller ◽  
Michael O'Connell ◽  
Thomas H. Cartwright ◽  
Christopher Twelves ◽  
Edward McKenna ◽  
...  

3522 Background: Studies show significantly improved disease-free and overall survival (DFS, OS) for oxaliplatin (Ox)-based vs. leucovorin/5-fluorouracil (LV/5-FU) adjuvant therapy in CC, with conflicting reports of Ox benefit in patients > 70 years old. The impact of MC on Ox benefit has not been assessed. We assessed the impact of age and MC on adjuvant treatment outcomes for stage III CC. Methods: N = 4,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT were analyzed by Ox therapy (XELOX/FOLFOX) vs. LV/5-FU, MC, and age; patients treated with bevacizumab were excluded. Endpoints were DFS (primary), OS, and safety. MC was assessed (except NSABP C-08) by adapted Charlson Comorbidity and NCI Combined Indices (CCI, NCI): Low (≤ 1) vs. high (> 1). Hazardratios (HR) were estimated by Cox regression analyses. Multivariate Cox regression analyses (MVA) tested for independent effects of age and MC on Ox benefit, controlling for gender, T, and N stage. Results: Patient demographics, MC, and disease characteristics (except lymph nodes examined) were well balanced across groups. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months). MVA-confirmed DFS/OS benefit was consistently shown for XELOX/FOLFOX vs. LV/5-FU, regardless of age or MC. Grade 3/4 serious adverse event (AE) rates were comparable across cohorts and CCI scores, and higher in patients aged ≥ 70. Grade 3/4 AEs of interest, including peripheral sensory neuropathy, were comparable across ages and CCI scores, and higher with XELOX/FOLFOX. Conclusions: Ox benefit is modestly attenuated in patients aged ≥ 70; however, significant benefit is observed regardless of age or MC in this analysis. Our results further support XELOX or FOLFOX as standard options for the adjuvant management of stage III CC in all age groups. [Table: see text]

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3525-3525
Author(s):  
Weijing Sun ◽  
Hans-Joachim Schmoll ◽  
Michael O'Connell ◽  
Thomas H. Cartwright ◽  
Christopher Twelves ◽  
...  

3525 Background: A fluoropyrimidine + Ox is the standard of care for stage III CC but a fluoropyrimidine alone is recommended for selected patients in several practice guidelines. We assessed efficacy and safety of adjuvant capecitabine ± Ox vs. LV/5-FU ± Ox across a population of stage III CC patients enrolled in four trials. Methods: N = 5,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT were pooled and analyzed; bevacizumab-treated patients were excluded. Endpoints were disease-free survival (DFS, primary), relapse-free survival (RFS), overall survival (OS), and safety. Multivariate Cox regression analyses (MVA) controlled for age, gender, T, and N stage. Results: Patient demographics and disease characteristics (except lymph nodes examined) were well balanced across groups. The number of patients receiving capecitabine and LV/5-FU were 1,942 and 3,877, respectively. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months). Five-year DFS was 62.8% for capecitabine ± Ox and LV/5-FU ± Ox. The capecitabine by Ox interaction was significant for OS with a trend for DFS and RFS; likely due to improved outcomes with capecitabine alone and similar outcomes for capecitabine or LV/5-FU + Ox. Serious adverse event (AE) rates were similar for LV/5-FU- and capecitabine-based therapy (16% vs. 20%, respectively). Overall, treatment-related grade 3/4 AEs were more common with LV/5-FU (59% vs. 47%). Treatment-related grade 3/4 AEs of interest included peripheral sensory neuropathy (5% vs. < 1%), diarrhea (12% vs. 15%), febrile neutropenia (2% vs. < 1%), and hand–foot syndrome (< 1% vs. 12%). Conclusions: Adjuvant capecitabine ± Ox and LV/5-FU ± Ox show comparableefficacy benefits for the treatment of stage III CC; further supporting capecitabine or LV/5-FU-based regimens as standard options for the adjuvant therapy of stage III CC. [Table: see text]


2009 ◽  
Vol 27 (19) ◽  
pp. 3109-3116 ◽  
Author(s):  
Thierry André ◽  
Corrado Boni ◽  
Matilde Navarro ◽  
Josep Tabernero ◽  
Tamas Hickish ◽  
...  

Purpose Three-year disease-free survival (DFS) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin (LV5FU2) with the addition of oxaliplatin (FOLFOX4). Final results of the study, including 6-year overall survival (OS) and 5-year updated DFS, are reported. Patients and Methods A total of 2,246 patients were randomly assigned to receive LV5FU2 or FOLFOX4 for 6 months. The primary end point was DFS. Secondary end points were OS and safety. Results Five-year DFS rates were 73.3% and 67.4% in the FOLFOX4 and LV5FU2 groups, respectively (hazard ratio [HR] = 0.80; 95% CI, 0.68 to 0.93; P = .003). Six-year OS rates were 78.5% and 76.0% in the FOLFOX4 and LV5FU2 groups, respectively (HR = 0.84; 95% CI, 0.71 to 1.00; P = .046); corresponding 6-year OS rates for patients with stage III disease were 72.9% and 68.7%, respectively (HR = 0.80; 95% CI, 0.65 to 0.97; P = .023). No difference in OS was seen in the stage II population. The incidence of second noncolorectal cancers was 5.5% and 6.1% in the FOLFOX4 and LV5FU2 groups, respectively. Among patients receiving oxaliplatin, the frequency of grade 3 peripheral sensory neuropathy was 1.3% 12 months after treatment and 0.7% at 48 months. Conclusion Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3523-3523 ◽  
Author(s):  
Christopher Twelves ◽  
Hans-Joachim Schmoll ◽  
Michael O'Connell ◽  
Thomas H. Cartwright ◽  
Edward McKenna ◽  
...  

3523 Background: Oxaliplatin-based adjuvant therapy is the standard of care for stage III colon cancer; however, its impact on PRS in these patients is unclear. We therefore compared PRS in trials of patients with stage III colon cancer treated with oxaliplatin plus capecitabine (XELOX) or 5-flourouracil (5-FU; FOLFOX) vs. leucovorin/5-FU (LV/5-FU). Methods: Individual patientdata (N = 4,819) from NSABP C-08, XELOXA, X-ACT, and AVANT were pooled and analyzed by XELOX/FOLFOX vs. LV/5-FU; patients treated with bevacizumab were excluded. Hazard ratios (HR) were estimated by Cox regression analyses and multivariate Cox regression analyses controlled for age, gender, T, and N stage. Post-relapse treatment data were collected when available. Results: Patient demographics and disease characteristics (except lymph nodes examined) were well balanced across analytic groups. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) than in XELOXA and X-ACT (83 and 74 months). PRS was very similar for XELOX/FOLFOX and LV/5-FU (HR 0.94, 95% CI, 0.82–1.07; P = .33). Multivariate analyses supported these findings, but showed that PRS was associated with younger age and lower N stage at diagnosis after controlling for gender and T stage. PRS was also comparable for capecitabine or XELOX vs. LV/5-FU or FOLFOX (N = 5,819, HR 1.07, 95% CI, 0.95–1.20; P = .26). Post-relapse therapies were comparable across the two cohorts. Conclusions: Adjuvant chemotherapy regimen did not impact on PRS in patients with stage III colon cancer; however, both N stage and age demonstrated independent effects on PRS. Studies have demonstrated significantly improved disease-free and overall survival for oxaliplatin-based therapy, and our data show that survival is not compromised by worsened PRS at subsequent relapse. [Table: see text]


ESMO Open ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. e000354 ◽  
Author(s):  
Masahito Kotaka ◽  
Takeharu Yamanaka ◽  
Takayuki Yoshino ◽  
Dai Manaka ◽  
Tetsuya Eto ◽  
...  

BackgroundThe International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).Patients and methodsACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.ResultsBetween August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).ConclusionsWe confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.Trial registration numberUMIN000008543, Results.


2018 ◽  
Vol 28 (3) ◽  
pp. 586-593 ◽  
Author(s):  
Mette Calundann Noer ◽  
Sofie Leisby Antonsen ◽  
Bent Ottesen ◽  
Ib Jarle Christensen ◽  
Claus Høgdall

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17517-e17517
Author(s):  
J. M. Davies ◽  
S. Lupichuk ◽  
E. Batuyong ◽  
R. J. Hilsden ◽  
J. Easaw

e17517 Background: The 2005 ASCO guidelines for surveillance following adjuvant therapy for CRC outlined recommended surveillance tests and their frequencies including history and physical examination, CEA testing, CT scan and colonoscopy. The purpose of this study was to assess the impact of these guidelines post treatment of stage II and III CRC in the Calgary Health Region (CHR) before and after implementation of a computer generated, personalized discharge letter (DL). Methods: Cohort 1 patients completed adjuvant chemotherapy or radiotherapy for stage II and III CRC between September 1, 2006, and November 30, 2007, prior to implementation of the DL. Cohort 1 was retrospectively identified from the Alberta Cancer Registry. Registry data was collated with laboratory data and diagnostic imaging data is forthcoming. Adherence to the guidelines at 1-year follow-up in cohort 1 was measured. Prospective data collection on patients who completed adjuvant treatment after implementation of the DL (cohort 2) is ongoing. Comparison of adherence rates to surveillance testing between the two cohorts will be reported upon study completion. Results: For cohort 1, 209 of 238 patients referred to the cancer centre were from the CHR and hence included in the analysis. The average age was 65 and 53% were male. Most patients (136/209) had stage III CRC. 1/209 had a local recurrence only. 27/209 progressed to metastatic disease during the 1-year follow-up period, of which 23 of these patients were initially diagnosed with stage III CRC. CEA adherence (≥4 tests taken within 1-year follow-up period) was 38.3% (95% CI 31.7–44.9). CT scan adherence and use of “inappropriate” surveillance testing for cohort 1 will be available at the meeting. Conclusions: This study assesses compliance with the 2005 ASCO CRC surveillance guidelines at 1-year follow-up post adjuvant treatment at a tertiary cancer centre. Analysis of cohort 1 reveals that adherence to CEA testing is suboptimal. The next phase of this study will assess the impact of a DL, sent to patients and primary care providers outlining recommended surveillance tests and dates, on adherence rates. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6014-6014
Author(s):  
Jenny J Ko ◽  
Hagen F. Kennecke ◽  
Howard John Lim ◽  
Sharlene Gill ◽  
Ryan Woods ◽  
...  

6014 Background: Research suggests that EPs with cancer are commonly undertreated, but the precise reasons for this observation are unclear. Our aims were to 1) evaluate the impact of advanced age on AC use (none vs capecitabine vs FOLFOX) for stage III CC, 2) determine the specific reasons for selecting and discontinuing a particular regimen, and 3) examine if the effect of AC on outcomes is modified by age. Methods: Patients diagnosed with stage III CC from 2006 to 2008 and referred to any 1 of 5 cancer centers in British Columbia, Canada were identified. Descriptive statistics were used to summarize treatment patterns in young patients (YPs) aged <70 vs EPs aged >/=70 years. Logistic regression was used to evaluate the association between AC and cancer-specific survival (CSS) in YPs and EPs. Results: We identified 810 patients: 51% men, 52% YPs and 48% EPs, and 74% received AC in the entire cohort. When compared to YPs, EPs had worse ECOG and more comorbidities (both p<0.01). EPs were less likely than YPs to receive AC (57 vs 91%, p<0.01). Frequent reasons for no treatment included age, comorbidities and perceived minimal benefit from AC. Among those treated with AC, EPs were less likely to receive FOLFOX (32 vs 74%, p<0.01) in favor of capecitabine due to patient preference, age and comorbidities. Once started on AC, EPs had similar rates of early treatment discontinuation as YPs (70 vs 62%, p=0.08). Reasons for early discontinuation were comparable between EPs and YPs (Table). Receipt of either FOLFOX or capecitabine was correlated with improved CSS, compared to surgery alone. Age did not modify CSS, irrespective of AC choice (interaction p for capecitabine and age=0.26; interaction p for FOLFOX and age=0.40). Conclusions: EPs with stage III CC frequently received either no adjuvant treatment or capecitabine monotherapy due to advanced age and comorbidities. The treatment effect of AC on CSS is similar across age groups, with comparable side effects and rates of discontinuation between EPs and YPs. AC should not be withheld from CC patients based on advanced age alone. [Table: see text]


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Julie Nicole Graff ◽  
Giulia Baciarello ◽  
Andrew J. Armstrong ◽  
Celestia S. Higano ◽  
Peter Iversen ◽  
...  

200 Background: In the phase 3 PREVAIL trial, enzalutamide (ENZA), an androgen receptor inhibitor, improved overall survival (OS) and radiographic progression-free survival (rPFS) relative to placebo (PBO) in chemotherapy-naïve men with mCRPC. Methods: PREVAIL randomized 1,717 patients (pts) with asymptomatic or minimally symptomatic chemotherapy-naïve mCRPC 1:1 to ENZA 160 mg daily or PBO. Coprimary endpoints were OS and rPFS. This prespecified analysis evaluated the impact of age (≥ 75 vs < 75 years) on efficacy and safety. Results: In PREVAIL, 609 (35%) pts were aged ≥ 75 years. This older subset had several poorer baseline prognostics relative to those aged < 75 years: worse ECOG performance status (ECOG 1: 45.0% vs 24.7%), higher prostate-specific antigen (PSA; 73.3 vs 37.3 ng/mL) and more cardiovascular disease (26.9% vs 16.5%). In both older and younger pts, ENZA improved OS, rPFS and time to PSA progression (Table). Pts aged ≥ 75 years in both the ENZA and PBO groups combined had a higher rate of grade ≥ 3 adverse events (46% vs 37% in younger pts) and among enzalutamide-treated men more older pts reported falls (any grade; ENZA 19% and PBO 8%) than younger pts (ENZA 7% and PBO 4%). Fewer pts ≥ 75 years received subsequent antineoplastic therapies. Conclusions: In PREVAIL, efficacy outcomes in elderly (≥ 75 years) and younger (< 75 years) pts with chemotherapy-naïve mCRPC were comparable and pts consistently benefited from ENZA treatment. Safety with ENZA was similar in both age groups, although older pts reported a higher incidence of falls and received fewer subsequent antineoplastic therapies. Clinical trial information: NCT01212991. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9578-9578
Author(s):  
Shirin Bajaj ◽  
Anthony Collado ◽  
Una Moran ◽  
Douglas MacArthur Donnelly ◽  
Paul Johannet ◽  
...  

9578 Background: The recently revised (AJCC) Staging Manual, 8th edition, introduced changes including removal of mitotic index and addition of the IIID substage. There is active debate on the utility of this revision, especially, without the inclusion of a novel prognostic biomarker, during an era of major therapeutic shifts and amidst accrual of adjuvant clinical trials for high-risk resected primary melanoma. We examined whether re-staging primary melanoma patients using the new AJCC 8 system yielded improved prognostication as compared to AJCC 7. Methods: We compared the impact of changes in staging criteria in stage I-III melanoma patients who were prospectively enrolled in a NYU clinicopathological database between January 2010 and December 2016 with active protocol-driven follow up (FU). We assessed primary tumor category (T) and nodal status (N) according to both AJCC 7 and 8. Progression free survival (PFS) and overall survival (OS) curves were generated for both editions and then stratified by substage. We analyzed discordance using Cox Regression Models. Results: 1,379 patients (56% male, mean thickness 1.6, median FU 34.8 months) were included in the analyses. All but one patient remained in the same ‘major’ stage using AJCC 7 and 8 (stage I- 998; II- 224, 225; III- 157, 156) whereas 44% of stage III substage classifications were discordant comparing AJCC 7 to 8. Despite removing mitoses as a criterion for Stage I, there was no significant change between editions in PFS/OS when evaluating major and substages of stage I. Stage IIC patients had worse PFS/OS than stage IIIA patients in AJCC 8 (PFS p = 0.04, OS p = 0.02). AJCC 8, which implemented four rather than three substages, had improved PFS prognostication (c-index = 0.59 vs 0.66, p = 0.05 for AJCC 7 vs 8). Conclusions: Our results reinforce the added value of AJCC 8 compared to 7, as removing an operator dependent variable is more practical for stage I, and increased influence of thickness/ulceration and the addition of a new substage is more prognostically informative for stage III. Nevertheless, the poor prognosis of stage IIC patients, despite nodal negative disease, continues to be an unaddressed gap within our current staging framework.


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