Safety Study of Capecitabine With Radiation in Elderly Rectal Cancer

Phase 1

Completed

Brief Summary: This phase I study is designed to determine the maximum tolerant dose of capecitabine when used in preoperative concurrent chemo-radiation for locally advanced rectal patients over 75 years old.

Detailed Description: It is proved that preoperative concurrent chemo-radiotherapy can improve both local control and overall survival in stage II/III rectal cancer patients. But elderly patients, especially patients over 75 years were hardly involved in related clinical trials considered of their fragility.

Several retrospective study showed that old rectal cancer patients would also benefit from concurrent chemo-radiation, with acceptable toxicity. Several new drug, such as capecitabine, also seem to be safety for elderly cancer patients. But few prospective study has been carried out.

The investigators designed this phase I study, to explore the maximum tolerant dose of capecitabine in preoperative concurrent chemoradiation for elderly stage II/III rectal cancer patients, as well as to evaluate safety.

Recruitment & Eligibility

Inclusion Criteria

rectal adenocarcinoma, clinical stage II/III(T3-4 or N+, AJCC 7th).
KPS status no less than 70; Charlson comorbidity no more than 3.
life expectancy more than 6 months.
hemoglobin >= 100g/L, white blood cell >= 3.5*10E9/L, neutrophil >= 1.5*10E9/L, platelet >= 100*10E9/L.Creatin normal, Total bilirubin normal, AST and AST normal, AKP normal.
do not have allergy history to thymidine phosphorylase.
do not receive surgery ( except palliative colostomy) or chemotherapy or other anti-cancer treatment
no previously pelvic irradiation history
informed consent signed

Exclusion Criteria

other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma
previous pelvic irradiation history
receiving surgery (except palliative colostomy), chemotherapy or other anti-cancer treatment
allergy history to thymidine phosphorylase
active infection existed
severe complication, such as acute myocardial infarction in 6 months, uncontrolled diabetes ( Plasma glucose concentrations in any time of a day≥11.1mmol/L）, severe cardiac arrhythmia， etc.
anticipate other clinical trials in four weeks before enrollment

Arm && Interventions

Group	Intervention	Description
1200mg	Capecitabine	capecitabine 1200mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
1000mg	Capecitabine	capecitabine 1000mg/m2/d d1-14, d22-25 combined with concurrent radiotherapy will be given to enrolled patients.
1500mg	Capecitabine	capecitabine 1500mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
1350mg	Capecitabine	capecitabine 1300mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.
1650mg	Capecitabine	capecitabine 1650mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experienced Dose Limited Toxicity	up to 7 weeks from start of the treatment	Dose related toxicity is defined as follows:1. luecopenia \> grade 2; granular cell decrease \> grade 2; anemia \> grade 1; platelet \> grade 1;SGPT/SGOT elevation \> grade 1; ALP \> grade 1; GGT \> grade 1; Tbil \> grade 1;renal function damag \> grade 2;Non-gradular cell decreased fever \> grade 1;nausea/vomiting \> grade 1; fatigue \> grade 2; weight loss \> grade 2;gastritis \> grade 2; dairrea \> grade 2; abdominal pain \> grade 2; upper gastrointestinal bleeding \> grade 1;other toxic reaction \> grade 2;KPS \< 50 during the treatment

Secondary Outcome Measures