A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma

Inclusion Criteria:

* Patients with histologically confirmed rectal cancer.
* Written Informed Consent
* Patients should be a candidate for preoperative radiotherapy
* A primary tumor of 3cm or greater with a clinical stage of T2, T3 or T4 and any N according to the Astler-Coller modification of the Dukes staging system
* Patient must be 18 years of age or older
* Must have an ECOG performance status of 2 or Less
* Diagnosis of rectal cancer should be no more than 90 days from initial clinic visit or from the start of therapy
* Patients must be seen and evaluated at the H. Lee Moffitt Cancer Center
* Patients must be recovered from prior surgery
* Patients must have a life expectancy of 3 months or greater
* Laboratory criteria: WBC of 3,500/mm3 or greater; Neutrophils of 1,500mm3 or greater; Platelet count of 100,000/mm3 or greater; Serum creatinine of 1.5 mg/dl or lesser; or creatinine clearance of greater than 60ml/min; SGOT/AST \& SGPT/ALT \& alkaline phosphatase of 2 times or lesser than the upper limit or normal if liver metastases are present; Serum bilirubin of 1.5mg/dl or lesser.

Exclusion Criteria:

* Patients with their primary tumor totally excised at time of diagnosis
* Patients with recurrent rectal cancer that failed initial treatment
* Patients previously treated with topotecan
* Patients with active infection
* Any known primary or secondary immunodeficiencies
* Any condition of the GI tract which would affect GI absorption or motility (e.g., autonomic neuropathy, active gastric or duodenal ulcers or certain gastrointestinal surgeries). Patients receiving medication to maintain motility or gastric emptying are also excluded.
* Patients with uncontrolled emesis, regardless of etiology.
* Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or a low grade prostate cancer.
* Concurrent severe medical problems unrelated to the malignancy which would significantly limit full compliance with the study or expose the patient to significant risk.
* Patients of child bearing potential, not practicing adequate contraception (barrier method or IUD for three months before the start of the study an agree to continue for at least 4 weeks after the end of the study)
* Patients who are pregnant or lactating
* Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.