10 Capecitabine based adjuvant therapy for stage III colon cancer — single institution experience

3608 Background: The National Quality Forum has endorsed the use of adjuvant chemotherapy in stage III colon cancer, yet a substantial treatment gap exists in the United States. Our objective was to evaluate the contribution of postoperative complications on the use of adjuvant therapy after colectomy for cancer. Methods: Patients from the National Surgical Quality Improvement Program and the National Cancer Data Base who underwent colon resection for cancer were linked (2006-2008). The association of complications on adjuvant chemotherapy use was assessed using multivariable regression models. Results: From 140 hospitals, 2368 patients underwent resection for stage III colon adenocarcinoma. Overall, 36.8% (871/2,368) patients were not treated with adjuvant therapy, of which 47.8% (416/871) had documented severe comorbidities or advanced age (≥80) as the reason for no adjuvant therapy receipt. Of the remaining 455 patients, 21.3% (97/455) had ≥1 serious complication that could account for adjuvant therapy omission. The remaining 41.1% (358/871) patients did not have a documented reason for not recieving adjuvant therapy. Complications associated with adjuvant therapy omission were abscess/anastomotic leak (OR 1.91, 95% CI 1.02-3.59), renal failure (OR 7.16, 95% CI 1.92-26.79), prolonged ventilation (OR 7.92, 95% CI 2.97-21.13), re-intubation (OR 5.69, 95% CI 2.13-15.18), and pneumonia (OR 4.05, 95% CI 2.07-7.90). Abscess/anastomotic leak was associated with a 28-day delay in time to adjuvant chemotherapy (73 vs. 45 days, p<0.05). Superficial surgical site infection did not decrease adjuvant therapy receipt but delayed the time to its use (57 vs. 44 days, p<0.05). The occurrence of postoperative sepsis was associated with a 15-day delay to adjuvant chemotherapy (60 vs. 45 days, p<0.05). Conclusions: Serious postoperative complications explained nearly one quarter of the adjuvant chemotherapy treatment gap among stage III colon cancer patients. Postoperative complications affect treatment utilization and should be considered when calculating adherence with the Stage III adjuvant therapy for colon cancer measure. Judging provider performance using quality metrics is challenging without clinical data.

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A novel interaction of genotype, gender, and adjuvant treatment in survival after resection of stage III colon cancer: Results of CALGB 89803.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3517 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3517-3517

Author(s):

Robert S. Warren ◽

Chloe Evelyn Atreya ◽

Donna Niedzwiecki ◽

Robert J. Mayer ◽

Richard M. Goldberg ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Therapy ◽

Survival Benefit ◽

Zinc Binding ◽

Stage Iii ◽

Therapy Regimen ◽

Domain Specific ◽

Stage Iii Colon Cancer ◽

Rational Choices ◽

And Gender

3517 Background: The p53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival is remains undefined. We investigated whether domain-specific mutations in p53 are predictive of survival in stage III colon cancer. Methods: p53 was evaluated in an intergroup trial (CALGB 89803) of patients with stage III colon cancer who were randomized to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL) Tissue was collected to allow correlation of molecular markers with outcomes. p53 was genotyped in 607 patient tumors. Results: p53 mutations were identified in 274 tumors, divided ~ equally between zinc binding and non-zinc binding regions of the DNA binding domain. Overall, p53 status was not predictive of benefit from either adjuvant regimen. Unexpectedly, the 5 year overall survival (OS) of women with tumors harboring non-zinc binding mutations treated with 5FU/LV was 97% compared to OS of 72% for women with p53 wild-type (wt) tumors (p =0.004). Adding irinotecan to 5FU/LV negated this survival benefit (5 year OS of 81% vs. 72%). Conversely, 5 year OS of women harboring tumors with zinc binding mutations who received 5FU/LV was 50% compared to 72% for women with p53 wt tumors (p=0.04). Adding irinotecan to 5FU/LV reversed the poor survival of women with tumors harboring zinc binding mutations and improved 5 year OS (50% vs. 73%; p=0.1). No difference in OS was observed for men on either treatment arm or when genotype was considered. Conclusions: CALGB 89803 demonstrated a lack of survival benefit for stage III colon cancer patients when irinotecan was added to 5FU/LV (IFL). We now show that in the setting of a large clinical trial, refined stratification of women, based upon domain- specific mutations of p53 identifies subsets of patients likely to benefit from, or respond poorly to, adjuvant 5FU/LV. The interaction of p53 genotype, gender, and adjuvant therapy regimen has the potential to be paradigm changing in the treatment of colon cancer, and possibly other malignancies. These data, if validated, suggest that evaluation of p53 genotype and gender may guide clinicians to make rational choices of adjuvant therapy.

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Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2010.33.6297 ◽

2011 ◽

Vol 29 (11) ◽

pp. 1465-1471 ◽

Cited By ~ 421

Author(s):

Daniel G. Haller ◽

Josep Tabernero ◽

Jean Maroun ◽

Filippo de Braud ◽

Timothy Price ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Therapy ◽

Folinic Acid ◽

Mayo Clinic ◽

Disease Free Survival ◽

Stage Iii ◽

Primary Study ◽

Primary Analysis ◽

Stage Iii Colon Cancer

PurposeThis multicenter, randomized trial compared capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil (FU) and folinic acid (FA) as adjuvant therapy for patients with stage III colon cancer.Patients and MethodsPatients who had undergone curative resection were randomly assigned to XELOX (oxaliplatin 130 mg/m2on day 1 plus capecitabine 1,000 mg/m2twice daily on days 1 to 14 every 3 weeks for 24 weeks) or a standard bolus FU/FA adjuvant regimen (Mayo Clinic for 24 weeks or Roswell Park for 32 weeks). The primary study end point was disease-free survival (DFS).ResultsThe intention-to-treat population comprised 1,886 patients; 944 patients were randomly assigned to XELOX and 942 to FU/FA (Mayo Clinic, n = 664; Roswell Park, n = 278). After 57 months of follow-up for the primary analysis, 295 patients (31.3%) in the XELOX group had relapsed, developed a new primary colon cancer, or died compared with 353 patients (37.5%) in the FU/FA group (hazard ratio [HR] for DFS, 0.80; 95% CI, 0.69 to 0.93; P = .0045). The 3-year DFS rate was 70.9% with XELOX and 66.5% with FU/FA. The HR for overall survival (OS) for XELOX compared to FU/FA was 0.87 (95% CI, 0.72 to 1.05; P = .1486). The 5-year OS for XELOX and FU/FA were 77.6% and 74.2%, respectively. Follow-up is ongoing. Preplanned multivariate and subgroup analyses supported the robustness of these findings.ConclusionThe addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer. XELOX is an additional adjuvant treatment option for these patients.

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