Background: Since 2004, 6 months of postsurgical adjuvant chemotherapy with combination of
5-FU/LV or oral Capecitabine and Oxaliplatin has been the standard of care worldwide for
patients with stage III colon cancer. Objectives: to evaluate the efficacy of 3-months of
Capecitabine and Oxaliplatin (CAPOX) followed by 3 months Capecitabine alone as adjuvant
treatment in stage III colon cancer.
Methods: This is a prospective study that included 50 patients with stage III colon cancer
who presented to National Cancer Institute, Cairo University to receive adjuvant CAPOX for
three months followed by three months Capecitabine alone where disease free survival (DFS)
& overall survival (OS) and toxicity were evaluated.
Results: The median age of patients was 43 years (range: 21-70) with male predominance.
The majority of patients (70%) had right-sided lesions and N1 stage (64%). After a median
follow up period of 36.8 months (range: 9.5-50.8); the 3-year cumulative DFS & OS were 57.2
& 86.3% respectively. Patients’ age, presence of comorbidity, higher grade, development of
chemotherapy-related peripheral neuropathy (PN), N2 stage, perineural invasion (PNI) and
lymph node ratio (LNR) > 0.25 were significantly associated with worse DFS whereas, the
latter two were significantly related to worse OS. Diarrhea, vomiting, hand-foot syndrome and
PN were the most common grade 3 toxicities. The latter was significantly higher in patients with
preexisting diabetes.
Conclusion: This small phase II study suggests that shorter duration of adjuvant oxaliplatin in
stage III colon cancer might be associated with less toxicity especially peripheral neuropathy but
still shows comparable survival to the six-months regimen. Further larger scale prospective
randomized trial is mandatory to confirm these results.
INTRODUCTION
Colorectal cancer is the second- and third-most common cancer in women
and men, respectively. In 2012, 614,000 women (9.2% of all new cancer cases)
and 746,000 men (10.0% of new cancer cases) were diagnosed with colorectal
cancer worldwide. Combined, in both sexes, colorectal cancer is the third-most
common cancer and accounts for 9.7% of all cancers excluding non-melanoma skin cancer (1). In Egypt, according to the results of the
National Population-Based Cancer Registry Program,
colon cancer is the 7th most common cancer as it
constitutes 2.63% of all cancer cases (2).
For patients with stage III (lymph node-positive)
colon cancer, 6 months of postsurgical adjuvant chemotherapy
with leucovorin modulated 5-fluorouracil
(5-FU/LV) was the standard of care from 1990 to 2004
based on clinical trials that demonstrated a 25% relative
reduction in mortality over surgery alone (3).
Since 2004, the combination of 5-FU/LV or oral
Capecitabine and Oxaliplatin became the standard of
care worldwide based on the findings from three large
trials; the MOSAIC trial, (NSABP) C-07 trial, and the
NO16968 study (4).
The important question was how many cycles of
Oxaliplatin should be administered with the objective
of reducing treatment duration, toxicity, and cost of
adjuvant therapy in colon cancer (4).
More recent data, support the plausibility of
shorter duration treatment without loss of efficacy.
Two studies, the MOSAIC and NSABP C-07, provided
evidence in support of changing to shorter-duration
FOLFOX doublet-based treatment (4).
Consequently, independent trials worldwide are
currently in progress to gather data and perform a
prospective combined analysis to answer the single
primary hypothesis that 3 months of adjuvant therapy
with Oxaliplatin-based chemotherapy is non-inferior to
the current standard of six months for patients with
stage III colon cancer (4).
The aim of this study is to evaluate the efficacy and
safety of 3-months (4 cycles) of Capecitabine and
Oxaliplatin (CAPOX) followed by 3 months (4 cycles)
Capecitabine alone as adjuvant treatment in stage III
colon cancer. The primary end point is DFS at 2 years
and secondary end points are OS, safety and toxicity.
PATIENTS AND METHODS
This is a prospective study that included 50 patients
with stage III colon cancer who presented to National
Cancer Institute, Cairo University for their adjuvant
treatment. Patients received CAPOX for three months
followed by three months Capecitabine alone.
Eligibility criteria: potentially curative surgical
resection of pathologically proven stage III colon adenocarcinoma
(any TN1/2M0), age ? 18 years, Eastern
Cooperative Oncology Group performance score of ? 2,
No previous chemotherapy, normal blood counts, liver
and kidney functions, pregnant or lactating patients and
those with history of other malignancies were excluded.
Treatment protocol: three months CAPOX followed
by three months Capecitabine. Oxaliplatin 130 mg/m2
IV infusion over two hours (day 1 every three weeks) in
combination with Capecitabine administered orally at a
dose of 1000 mg/m2 twice-daily for two weeks and one
week off, followed by oral Capecitabine in the same dose
for 3 more months. Chemotherapy related toxicities
were assessed after each cycle of chemotherapy
treatment and were graded based on NCI-CTCAE, V 4.0.
Oral dose modification in response to adverse events
and toxicity was conducted on the basis of standard
clinical practice.
Statistical analysis
Statistical analysis was done using IBM SPSS®
Statistics version 22 (IBM® Corp., Armonk, NY, USA).
Numerical data were expressed as mean and standard
deviation or median and range as appropriate, while
qualitative data were expressed as frequency and
percentage. Survival analysis was done using Kaplan-
Meier method and comparison between two survival
curves was done using log-rank test. All tests were
two-tailed. A p-value < 0.05 was considered significant.
OS was calculated from the date of enrolment in the
study until the date of death or lost follow up. DFS was
calculated from the date of curative surgical resection
until the date of relapse, death or lost follow up.
RESULTS
The mean age of the studied group was 46.5±14.1
years, ranging between 21 and 70 years, while the
median was 43 years with male predominance (60%).
Sixteen percent of the patients presented with complications
in the form of obstruction and bleeding per
rectum. Right side affection was predominant (70%).
Preoperative serum CEA and CA 19.9 were measured in
19 patients. CEA was high in 2 patients (10.5%), while
CA 19.9 was normal in all patients. Postoperative serum
CEA and CA 19.9 was normal in all patients.
Clinicopathological characteristics of 50 cases of
restricted stage III colon cancer was shown in tables 1, 2.
Adenocarcinoma being the main pathological type
(52%) followed by mucinous adenocarcinoma (36%).
Grade 2 disease was more common than grade 3 and
T-stage at diagnosis was T3 in 80% of cases. The
median number of total lymph nodes removed during
surgery was 20 (range: 8-41). The majority of patients
(92%) had ? 12 nodes removed. Positive nodes were
> 3 in 18 patients (36%). Median lymph node ratio
(defined as number of positive lymph nodes/the number of total lymph nodes) was 0.12 (range: 0.02-0.72) with a
cutoff point of 0.25 used to correlate with DFS and OS.
Lymphovascular and perineural involvement was
reported in 19 and 5 cases out of 40 known cases,
respectively, while lymph node capsular involvement
was reported in 6 out of 41 known cases (14.6%) as
showing in table 2.
Three months CAPOX followed by three months
Capecitabine was administered to 47 patients; as three
patients decided to take standard treatment with 6
months CAPOX after enrollment in the study.
Treatment adherence (i.e., the percentage of patients
who received all planned therapy) was 95.7%.
The median follow up period of the studied group
was 36.8 months (range: 9.5-50.8 months), while the
cumulative DFS proportion at 36 months of the whole
studied group was 57.2%. Patients’ age (? 40) and
presence of comorbidity were associated with a worse
DFS (p = 0.015, p = 0.002, respectively). Table 3 shows DFS in relation to demographic and clinical prognostic
factors.
DFS was significantly worsened by presence of more
than 3 positive lymph nodes (nodal stage N2) (p < 0.001),
higher grade (p = 0.011), perineural involvement
(p < 0.001) and a lymph node ratio > 0.25 (p < 0.001).
Table 4 shows DFS in relation to tumor-related
prognostic factors.
The median OS was not reached by the end of the
study while the overall cumulative survival proportion
of the whole studied group was 86.3%. OS was not
significantly affected by age (p = 0.851), sex (p = 0.249),
comorbidity (p = 0.290), family history (p = 0.067), and
performance status as shown in table 5.
Perineural involvement was associated with
significantly worse OS (p = 0.001) as well as a lymph
node ratio > 0.25 (p = 0.027) as table 6.
DISCUSSION
Since 2004, oxaliplatin with a fluoropyrimidine has
been standard adjuvant chemotherapy in patients with stage III and high-risk stage II colon cancer. Three phase
3 trials convincingly showed that the addition of
oxaliplatin improved DFS; with longer follow-up, these
findings were extended to overall survival (5).
Accordingly, a 6-month regimen of FOLFOX
(fluorouracil, leucovorin, and oxaliplatin) or CAPOX
(Capecitabine and Oxaliplatin) became the standard
adjuvant therapy in stage III disease (6).
The risk of oxaliplatin-based sensory neurotoxicity
depends on the cumulatively administered dose of the
drug. Neurotoxicity often peaks several months after
the last oxaliplatin exposure, which makes empirical
dose individualization difficult. Such toxic effects can be
severe and persist long beyond the actual treatment,
which potentially affects patients’ activities of daily
living for the rest of their lives (6).
Therefore, this prospective study was designed to
evaluate the efficacy and safety of 3-months (4 cycles)
of CAPOX followed by 3 months (4 cycles) Capecitabine
alone as adjuvant treatment in stage III colon cancer.
This regimen was evaluated for its effect on delaying or
preventing recurrences, its impact on both DFS and OS
as well as evaluation of its toxicity. The study included
50 patients with stage III colon cancer who were
treated at NCI, Cairo University. Their age ranged from
21 to 70 years with a mean of 46.5±14.1 years. An
important remark in the current series is that, patients
40 years or younger constituted thirty-six percent of the
studied group with male predominance. However, it is
consistent with age distribution in previous published
hospital-based studies from Egypt which report that
more than one third of colorectal cases are younger
than 40 (7) (8).
Population based studies also have shown high CRC
rates at young age. Ibrahim et al., reported that the
average age is 50 years old in Egypt. While another
population-based study showed that the incidence rate
of CRC for those less than 40 years of age in Egypt was
22.0% of all cases, which is higher than the United
States incidence rate for the same age group with male
to female ratio of 1.2:1 (2) (9).
Family history criteria and pathologic features of
tumors in young Egyptian patients do not differ significantly
from those in older patients implying that they
are likely to have a similar etiology. Hereditary risk factors
are unlikely the cause associated with this unusual
pattern of early-onset CRC in Egyptian patients (10).
The increase in colon cancer in younger patients has
been previously reported. Siegel et al., demonstrated
an increased incidence of CRC in men and women
under the age of 50 at a rate of 2.1 percent per year
from 1992 through 2012 with incidence and mortality
rates of 30% and 40% higher in men than in women,
respectively (11).
Reasons for higher rates in men are not completely
understood, but to some extent likely reflect differences
in exposures to risk factors and sex hormones, as well as
complex interactions between these influences (12).
All patients presented with different grades of symptoms
before curative treatment. The most common
clinical presentation of the studied group was pain
(42%), followed by intestinal obstruction (36%).
Three of our patients (6%) had history of previous
appendectomy. Although studies have rarely investigated
whether appendicitis truly increases the cancer risk, and
its mechanism a follow-up study using large Asian
population data showed that patients with appendicitis
are at an elevated risk of colorectal cancer after
appendectomy. The overall risk elevation is estimated
to be 14%, but is much greater in elderly patients (13).
On the other hand, in a Swedish trial, no excess
gastrointestinal cancer risks were observed among
patients with previous appendectomy, with the
possible exception of esophageal cancer (14).
The most common site of cancer was the ascending
colon (44%), followed by cecum (20%). Collectively,
35 patients (70%) had right sided lesions (RCC) and
15 (30%) had left sided lesions (LCC). There was no
significant survival difference between both sides in the
current study which may be due to the small number of
patients recruited.
Currently, data on the prognosis for patients with
nonmetastatic RCC and LCC are conflicting, and
whether the tumor's location itself has a significant
prognostic impact remains a matter for debate (15).
Previous studies have also reported that patients
with stage III RCC likely present a significantly increased
mortality risk compared with those with LCC. By
analyzing various stages of colorectal cancer, Huang et
al., observed a poorer OS in patients with RCC than
those with LCC, whereas significant differences were
only noted in stage III patients (16).
For patients treated with curative resection and
subsequent oxaliplatin-based adjuvant chemotherapy,
Sinicrope et al., found that RCC was significantly
associated with a shorter DFS than LCC in patients with
BRAF wild type stage III colon cancer (17). Similarly,
Zhang et al, demonstrated that both the 5-year
recurrence-free survival and 5-year OS were significantly
different; survival gradually decreased for caecal tumors
till the sigmoid tumors (18).
However, how many adjuvant chemotherapy cycles
were administered was not discussed in the abovementioned
studies. In a retrospective study, Peng et al.,
demonstrated that tumors arising on different sides
generate different prognostic outcomes in patients with
stage III colon cancer who received adjuvant
chemotherapy after curative resection. The full course
of adjuvant chemotherapy might only benefit RCC
patients. However, the underlying mechanisms creating
different outcomes after a full course of adjuvant
chemotherapy for RCC and LCC remain unclear. They
considered that advanced tumors were more frequently
observed on the right side, and these tumors might
benefit from more intensive chemotherapy (19).
Although most studies showed poorer survival for
primary tumors located on the right side, a study by
Weiss et al., demonstrated no difference between the
5-year OS for patients with RCC and LCC after adjusting
for multiple variables; instead, they found that the
mortality in patients with stage II RCC was lower than it
was in those with LCC (20). A population-based
Surveillance, Epidemiology, and End Results (SEER)
analysis of patients with nonmetastatic colon cancer
provided evidence that the prognosis for patients with
RCC was better regarding OS and cancer-specific
survival (CSS). Subgroup analyses of patients with
stages III colon cancer showed that the prognosis for
RCC and LCC patients was similar (15).
Until now, heterogeneity within the literature,
including the study designs, disease stages, and
treatment information, has been significant. Additional
research is required to define the factors and tumor
biology more clearly with regard to colon cancer
laterality (15).
In the current study, adenocarcinoma was the main
pathological type of colon cancers (56%), followed by
mucinous adenocarcinoma (36%) with signet ring
carcinoma comprising (6%) while undifferentiated
carcinoma (2%). Pathological grade II was identified in
(78%) of cases while (22%) were grade III.
This is consistent with Foda et al, study showing
excess mucinous carcinoma among Egyptians,
especially signet ring variant in comparison with the
world rates (8).
The majority of our patients (92%) had ? 12 nodes
excised during surgery and > 3 positive nodes were
identified in 18 patients (36%). Lymphovascular
involvement was reported in 19 out of 40 known cases
(47.5%) and it was associated with worse DFS
(P < .0001) but not with OS.
Perineural involvement was reported in 5 out of 40
known cases (12.5%) while, Lymph node capsular
involvement reported in 6 out of 41 known cases
(14.6%).
The lymph node ratio defined as number of positive
lymph nodes / the number of total lymph nodes
evaluated in our study revealed that a cutoff point of 0.25 was significantly affecting both DFS (P < .0001) and
OS (p = 0.027).
Lymph node ratio independently predicts prognosis
in stage III colon cancer and may thus act as a
confounder. Previous reports of
The prognostic significance of total number of
lymph nodes in node-positive colon cancer were
confounded by lymph nodes ratio. The 12-node
standard for total number of lymph nodes may not be
equally applicable in right-sided and left-sided colon
cancer. SEER database of 63,243 stage III patients
with colon cancer were identified by Yang et al, who
reported that after adjusting for lymph nodes ratio, the
association of the total number of lymph nodes with
survival in stage III colon cancer was present only in
right-sided colon cancer but not in left-sided colon
cancer (21).
In the current study, the median follow up period of
the studied group was 36.8 months. The cumulative
DFS proportion at 36 months of the whole studied
group was 57.2%. Patients’ age and presence of
comorbidity were associated by worse DFS (p = 0.015,
p = 0.002, respectively).
DFS was significantly worsened by presence of more
than 3 positive lymph nodes (p < 0.001), higher grade
(p = 0.011), nodal stage N2 (p = 0.001), and perineural
involvement (p < 0.001). Also, patients who develop
chemotherapy-related peripheral neuropathy had worse
DFS (p = 0.005) While it is not affected by Sex, positive
family history nor treatment-related prognostic factors.
In the current study at 36 months the cumulative OS
proportion of the studied group was 86.3%. Perineural
involvement was associated with significantly worse OS
(p = 0.001) also, longer time period between diagnosis
and surgery was associated with better OS (p = 0.001)
which may reflect indolent disease. On the other hand,
time from surgery to chemotherapy and duration of
chemotherapy did not affect overall survival.
OS was not significantly affected by age, sex, comorbidity,
family history or performance status. Otherwise,
the remaining tumor-related factors or toxicity-related
prognostic factors did not affect OS.
Survival outcomes in our study were compared with
trials that examined CAPOX as adjuvant treatment in
stage III colon cancer for 6 months. CAPOX in adjuvant
colon cancer treatment (XELOXA) trial investigated the
addition of oxaliplatin to an oral fluoropyrimidine in the
adjuvant treatment of colon cancer. CAPOX was
compared with bolus FU/FA in patients with stage III
colon cancer. The median number of chemotherapy
cycles received was 8.0 (range, 1 to 9) in the CAPOX
group (22).
The 3-year DFS rate was 70.9% with CAPOX being
superior to the bolus FU/FA (66.5%) with a HR of 0.80
(95% CI, 0.69 to 0.93; P .0045). The hazard ratio for OS
for CAPOX compared to FU/FA was 0.87 (95% CI, 0.72 to
1.05; P .1486). The 5-year OS for CAPOX and FU/FA
were 77.6% and 74.2%, respectively (22).
The 3-year DFS rates in both arms of XELOXA trial is
better than DFS in our study which is suggested to be
due to differences in clinicopathological criteria
between studied groups. The median age for patients in
XELOXA trial was 61 years old in the CAPOX arm and 62
years old in the bolus FU/FA arm. In our studied cohort,
the median age was 43 years old. Thirty-six percent of
the studied cohort was below 40 years of age. More
mucinous adenocarcinoma were reported in the
current study (36%) compared with that in the XELOXA
trial (22). Forty six percent of patients in our study
presented with complications in the form of intestinal
obstruction (36%) and rectal bleeding (10%).
Another randomized phase III trial of FOLFOX versus
CAPOX as adjuvant chemotherapy in patients with
early-stage colorectal adenocarcinoma conducted by
Pectasides was conducted. It randomized 201 patients
to FOLFOX and another 213 to CAPOX for 6 months.
Three-year DFS was 79.8% (95% CI 76.5-83.4) in the
FOLFOX group and 79.5% (95% CI 75.9-83.1) in the
CAPOX group (p=0.78). Three-year OS was 87.2% (95%
CI 84.1-91.1) and 86.9% (95% CI 83.4-89.9) in the in
FOLFOX and CAPOX groups respectively (23).
Inclusion of stage II in that trial explains high DFS in
comparison to our trial, SCOT was a randomized, phase
III noninferiority trial conducted in several European
countries conducted on 6,088 patients with high-risk
stage II/III colon cancer. Patients were randomized to
receive either 3 or 6 months of adjuvant CAPOX or
FOLFOX (24).
SCOT is significant in that it enrolled the largest
number of patients treated with CAPOX. The results
showed that a 3-months adjuvant chemotherapy was
noninferior to 6-months therapy in patients with stage
III colon cancer, with the same 3-year DFS rate in both
groups (HR, 1.015; 95% CI, 0.909-1.132). A post-hoc
analysis of 3-year DFS for patients in the CAPOX group
revealed that 3 months of CAPOX therapy was
significantly noninferior to 6 months of therapy. The
3-year DFS was 76.9% in the 3-months therapy group vs
76.1% in the 6-months therapy group (HR, 0.944; 95%
CI, 0.835-1.067; P [for noninferiority] = .002). While, 3
years OS was 90% for 3 months group and 89.6 for 6
months group (24).
ACHIEVE was another phase III trial conducted in
Japan that randomized patients with stage III colon cancer to receive either 3 or 6 months of mFOLFOX6 or
CAPOX adjuvant chemotherapy. A total of 1,313
patients were randomized (15% T1/T2, 57% T3, 28% T4,
and 26% N2) (25).
The 3-year DFS rate in ACHIEVE trial was 79.5% in
the 3-months group and 77.9% in the 6-months group
(HR, 0.954; 95% CI, 0.758-1.201). Subgroup analysis
revealed that the HR was 0.811 (95% CI, 0.532-1.236) in
patients with low-risk features (T1-T3 and N1) and
1.066 (95% CI, 0.810-1.403) in patients with high-risk
features (T4 or N2). HR was 1.065 (95% CI, 0.709-1.600)
in patients treated with FOLFOX and 0.904 (95% CI,
0.684-1.195) in those treated with CAPOX (25).
Hand and foot syndrome was the most common
encountered treatment toxicity in the current study,
(44.6%), followed by diarrhea (40.4%) and peripheral
neuropathy (30%).
In general grade 2 or 3 toxicity occurred in 35
patients (72.9%), while 13 patients (27.1%) had grade 1
toxicity and 7 patients had Grade 3 toxicity (14.7%).
None of our patients had grade 4 toxicity of any type.
The most common grade III toxicity was diarrhea
(6.3%), followed by vomiting (4.2%), peripheral
neuropathy (2.1%) and Hand-foot syndrome (2.1%).
Our study reports neutropenia to be presented in
(2.1%) which was better than that seen in Pectasides
study where the most common grade 3-4 toxicities
were neutropenia (13.8% with FOLFOX vs 4.4% with
CAPOX, p<0.0001) and Vomiting was more frequent in
the CAPOX group (1.6% vs 0%, p=0.017) (23).
The primary safety concern with the use of
oxaliplatin is peripheral neuropathy, a cumulative doserelated
toxicity. In this study, peripheral neuropathy
grade 1 occurred in (17%) of cases, while (10.6%) and
(2.1%) had grade 2 and 3 respectively.
Treatment related peripheral neurotoxicity was
significantly higher in association with comorbidity
(p = 0.018). There was no relation between age, comorbidity,
or timing of treatment with grade 2 or 3 of other
toxicity types.
These findings are consistent with the results from
Pectasides et al, where sensory neuropathy was
reported to be (3.2% with FOLFOX vs 2.1% with CAPOX,
p=0.25). While, in XELOXA trial grade 3/4 neurosensory
toxicity was evident in 11% of CAPOX - treated patients
for 6 months (22).
In the IDEA trial the shorter duration of adjuvant
therapy was associated with significantly lower rates of
adverse events than a longer duration, independent of
the chemotherapy regimen. Peripheral neurotoxicity of
grade 2 or higher during active therapy and in the
month after cessation of treatment was substantially
lower in the 3-months therapy group (16.6% with
FOLFOX and 14.2% with CAPOX) than in the 6-months
therapy group (47.7% with FOLFOX and 44.9% with
CAPOX). In addition, rates of diarrhea, neutropenia,
thrombocytopenia, nausea, mucositis, fatigue, and the
hand–foot syndrome were also substantially lower with
shorter treatment duration (26).
In SCOT, the frequency of grade ? 3 toxicities
was significantly higher in the 6-months than in the
3-months group (59% vs 36%; P < .0001): diarrhea (17%
vs 12%; P = .033), neutropenia (14% vs 10%; P = .031),
pain (6% vs 2%; P = .014), and hand-foot syndrome (5%
vs 2%; P = .031). Peripheral neuropathy of grade 2 or
worse was more common in the 6 months group (58%)
than in the 3 months group (25%) and was long-lasting
associated with worse quality of life (24).
While, in ACHIEVE trial, the frequency of grade ? 2
neurotoxicity was significantly lower in the 3-months
therapy group than in the 6-months group (14% vs
36%; P < .001) (25).
Peripheral neuropathy of more than grade 2 in our
study was 12.7% which is consistent with 3-months
therapy group in ACHIEVE trial and less than shown in
SCOT trial.
The findings reported here should be viewed with
the limitations of the single arm with small sample size
of the study and also clinicpathological differences of
colon cancer in Egypt.
CONCLUSION
This preliminary small sized phase II clinical study
using adjuvant (CAPOX) following curative surgical
treatment for stage III colon cancer patients had shown
less toxicity by reducing the dose of Oxaliplatin to only
three months especially peripheral neurotoxicity with
still comparable survival to the six months regimen.
The cumulative DFS proportion at 36 months of the
whole studied group was 57.2% while OS was 86.3%.
Special patient's characteristics were found to affect
the result of treatment as patient's age and presence of
comorbidity which were associated by worse DFS. In
addition, DFS was significantly worsened by lymph
node ratio of more than 0.25, higher grade, nodal stage
N2, perineural involvement and developing chemotherapy
- related peripheral neuropathy.
Perineural involvement and lymph node ratio of
more than 0.25 was associated with significantly worse
OS. Larger prospective randomized comparative study
is required to evaluate the non-inferiority of 3 months
CAPOX followed by Capecitabine than 6 months CAPOX
for stage III colon cancer. Also, to assess the safety and cost effectiveness in view of recent recommendations
for patient's classification in order to personalize
treatment decisions which offers great opportunity for
selecting the right therapies for our patients in the
future.
Conflict of interest
All author declare that they have no conflict of
interest.
Ethical approval
The study was approved of the Ethical Committee
in National Cancer Institute.
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