Annual Meeting Proceedings Part 1 - American Society of Clinical ...

3605 General Poster Session (Board #35B), Mon, 8:00 AM-12:00 PM
Phase II study of preoperative radiation with concurrent capecitabine,
oxaliplatin, and bevacizumab followed by surgery and postoperative 5-FU,
leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally
advanced rectal cancer: A trial of the Eastern Cooperative Oncology Group
(E3204). Presenting Author: Steven J. Cohen, Fox Chase Cancer Center,
Philadelphia, PA
Background: Oxaliplatin and bevacizumab potentiate the antitumor activity
of fluoroyprimidines and radiotherapy in preclinical and clinical studies of
colorectal cancer. This phase II trial evaluated the efficacy of the preoperative
combination of capecitabine, oxaliplatin, and bevacizumab with
radiotherapy in rectal cancer. Methods: Eligibility: resectable T3/T4 adenocarcinoma
of the rectum � 12 cm. from anal verge. Preoperative treatment
was capecitabine (825 mg/m² bid M-F), oxaliplatin (50 mg/m² weekly),
bevacizumab (5 mg/kg D1,15,29), and pelvic external beam radiotherapy
(50.4 Gy/28 fractions). Surgery was performed within 6-8 weeks. Within
12 weeks of surgery, patients received 12 cycles of FOLFOX � bevacizumab
(5 mg/kg) Q2 weeks. Pathologic complete response (path CR) was
the primary endpoint. Secondary endpoints included resection rate and
toxicity. Results: Fifty-seven patients (pts) enrolled from 7/06 to 5/10 and
54 were eligible. Clinical staging: T3/4 (50/4), NX0/1/2 (2/16/31/5). Most
common grade 3/4 non-hematologic toxicities during treatment were rectal
pain (9), fatigue (8), and diarrhea (7). Two patients died of aspiration. Nine
pts had early postsurgical complications (9 wound infections, 6 dehiscence,
1 abscess) and 23 had late surgical complications (23 non-healing
wounds, 12 dehiscence, 5 bowel obstruction/ileus, 2 abscess). Pathologic
staging: T0/1/2/3 (11/3/15/19), N0/1/2 (32/10/7). Nine pts had path CRs
(17%, 90% CI:[9%-27%]. Surgery was LAR (38) and APR (11). Twentytwo
pts did not receive postoperative chemotherapy (39%), 16 due to
adverse events. Five local recurrences have been reported. RFS and OS
data are immature. Conclusions: The addition of oxaliplatin and bevacizumab
to capecitabine and radiotherapy for locally advanced rectal cancer
resulted in downstaging for the majority of pts but did not improve the
pathologic complete response rate compared to historical controls. The
combination resulted in significant early and late postsurgical complications.
3607 General Poster Session (Board #35D), Mon, 8:00 AM-12:00 PM
Six months versus twelve months of capecitabine as adjuvant chemotherapy
for stage III (Dukes’ C) colon cancer: Initial safety report for the
open-label randomized phase III study (JFMC37-0801). Presenting Author:
Katsuyuki Kunieda, Gifu Prefectural General Medical Center, Gifu,
Japan
Background: The standard treatment duration of adjuvant chemotherapy
(CT) in patients (pts) with stage III colon cancer is 6 months. On the other
hand, no clinical trial showed the optimal treatment duration of oral
chemotherapeutic agents in adjuvant setting for colon cancer. Sargent et al
have reported that 83% of recurrences in stage II and III pts have occurred
within the first 3 years after surgery and peak was observed around one year
after surgery. Therefore, to clarify the benefit of 12 months administration
of Capecitabine, we designed randomized phase III trial for a comparison of
6 months treatment and 12 months treatment of capecitabine as adjuvant
CT for stage III colon cancer. Methods: JFMC37 is a multicenter, randomized
Phase III trial. Patients with fully resected Stage III colon or recto
sigmoid cancer were eligible. Capecitabine was administered orally as
tablets, 2,500 mg/m²/day for 14 days followed by a 7-days rest. Treatment
is continued to 8 cycles (6 months) in arm A (A) or 16 cycles (12 months) in
arm B (B). Patients were randomized 1:1 to A or B. Data size was estimated
by disease free survival as primary endpoint. The statistical design is based
on superiority hypothesis; 5-yrs DFS is 60% in arm A, 67% in arm B
;unilateral ��0.05, 1-��0.8;and planed accrual is 1200 pts. Results:
Between September 2008 to December 2009, 1304 patients were
enrolled and then randomized. Both arms were well balanced for mean age:
(A) 64.1, (B) 63.8; ECOG PS (%0/1): (A) 95.0/5.0, (B) 97.1/2.9;
involvement of lymph nodes (%N0/N1/N2): (A) 77.1/19.9/3.1, (B) 76.6/
19.7/3.7. Treatment completion rate for A and B were 68.2% and 43.4%.
Incidences of serious adverse events (SAEs) over 1% were neutropenia: (A)
2.6%, (B) 3.8%, diarrhea: (A) 2.9%, (B) 2.1%, loss of appetite: (A) 1.3%,
(B) 1.0%, fatigue: (A) 1.8%, (B) 1.2%, hand-hoot syndrome: (A) 16.4%,
(B) 22.1%. Conclusions: There were no obvious differences in SAEs
between arm A and arm B. Although twelve months of capecitabine showed
a tendency to increase G3/4 hand-foot syndrome, we concluded that
incidence of SAEs were acceptable and comparable to previously report.
Gastrointestinal (Colorectal) Cancer
229s
3606 General Poster Session (Board #35C), Mon, 8:00 AM-12:00 PM
Prognostic significance of intermediate mucinous carcinoma in patients
with microsatellite stable stage II or III colon cancer. Presenting Author:
Gun Min Kim, Department of Internal Medicine, Yonsei University College
of Medicine, Seoul, South Korea
Background: Mucinous adenocarcinoma (MC) is a histological subtype of
colorectal cancer with �50% of mucinous component of tumor volume.
According to WHO classification, tumor less than 50% of the lesion
composed of mucin was considered as non-mucinous carcinoma (NMC).Mucinous
histology has been shown to be an independent adverse prognostic
factor in some studies, but not in others. However, prognostic implication
of intermediate mucinous carcinoma (IMC) which had focal mucinous
component �50% of tumor volume has not been studied yet. The aim of
this study is to explore prognostic impact of IMC in patients with resected
stage II or III colon cancer. Methods: This study involved 917 patients who
underwent curative resection for stage II or III colon cancer in Severance
Hospital, from 2003 to 2009. The proportion of mucinous component was
reviewed and re-classified correctly by pathologists. MC was defined tumor
having �50% mucinous component. Tumor with mucinous component but
less than 50% regarded as IMC and less than 10% mucin as NMC. Results:
Among 917 patients, 63 (6.9%) and 60 (6.5%) were MC and IMC,
respectively. Median follow-up duration was 50.2 months (0.9~109.7) and
Stage 3 was 48.1% (441/917). The similarities between MC and IMC were
found as right colon dominant (MC: IMC: NMC � 60%: 67%: 34%,
p�.001) and higher incidence of MSI-high compared to NMC (MC: IMC:
NMC � 27%: 30%: 11%, p�.001). In stage III, the disease-free survival
(DFS) rate at 5 years was 44% for MC, 56% for IMC, and 74% for NMC
(p�.001). Subgroup analysis according to MSI status showed that DFS had
significant inverse correlation with proportions of mucinous components in
MSI-low or MSS group, but patients with MSI-high tumor showed higher
five-year DFS rate (�85%) regardless of mucinous component. For stage II
colon cancer patients, both mucinous histology and MSI had little clinical
significance. Conclusions: In patients with curative resection for stage II or
III colon cancer, IMC had similar characteristics to MC, which were right
colon dominant and high incidence of MSI-high tumor. The prognostic
impact of IMC was intermediate risk between MC and NMC in stage III
patients with MSI-low or MSS tumor, but not in MSI-high group.
3608 General Poster Session (Board #35E), Mon, 8:00 AM-12:00 PM
Effect of postoperative complications on adjuvant chemotherapy use in
stage III colon cancer. Presenting Author: Ryan P. Merkow, Northwestern
University, Feinberg School of Medicine, Chicago, IL
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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