Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma

The proposed protocol aims to continue tumor-directed therapy during the typical "break
period" in an effort to improve on both local tumor response as well as distant disease
control. First, the duration from completion of chemoradiotherapy would increase from 6-8
weeks to 9-11 weeks. As noted above, this may allow for further cell death with resultant
pathologic downstaging. Secondly, the protocol calls for continued systemic therapy during
the 9-11 week period, thus allowing continuation of therapies directed towards both the
primary as well as distant sites of disease. The primary aim of this pilot study would be to
establish the feasibility of this intensified neoadjuvant approach, especially with respect
to tolerability of the subsequent pelvic surgery. A subsequent phase II portion will evaluate
the efficacy of this treatment approach.

Inclusion Criteria:

1. Signed study-specific informed consent form

2. Age > 18 years old

3. Zubrod performance status 0-1

4. Biopsy proven primary malignancy

5. AJCC Stage II or III disease (T3-4 and/or N1-2 disease) as determined by endoscopic
ultrasound and/or MRI staging

6. Pretreatment rectal endoscopic ultrasound and pelvic MRI, colonoscopy, CT of chest,
abdomen, and pelvis, and laboratory values as discussed below

Exclusion Criteria:

1. History of inflammatory bowel disease

2. Previous pelvic radiotherapy

3. A major psychiatric illness which would limit understanding of the proposed protocol
treatment and consent process.

4. Men and women of reproductive potential must agree to use an effective contraception
method

5. Pregnant or lactating women

6. Severe, active co-morbidity, defined as

- Unstable angina and/or CHF requiring hospitalization within the last six months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

7. Presence of metastatic disease, including liver metastases

8. Laboratory values out of range