capecitabine as second-line therapy in treating patients with stage iv pancreatic cancer who have the thymidylate synthase gene

Conditions: Pancreatic Cancer

Summary: rationale: drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. purpose: this phase ii trial is studying how well capecitabine works as second-line therapy in treating patients with stage iv pancreatic cancer who have the thymidylate synthase gene.

objectives: primary * characterize the 6-month survival of patients with stage iv pancreatic cancer (progressing after at least 1 prior gemcitabine-containing chemotherapy regimen) who carry the double tandem repeat (s/s) variant of the thymidylate synthase (ts) gene enhancer region (tser) treated with capecitabine. * characterize toxicity of capecitabine in patients with stage iv pancreatic cancer who carry the s/s variant of the tser. secondary * explore the association between capecitabine exposure at steady-state, allelic variants in candidate genes (carboxylesterase 1, carboxylesterase 2, cytidine deaminase, thymidine phosphorylase \[tp\], dihydropyrimidine dehydrogenase \[dpd\], methylenetetrahydrofolate reductase) and drug response (toxicity and efficacy) in this patient population. * determine the relationship between expression of ts, tp, and dpd in tumor tissues and the response to capecitabine in this patient population. * analyze response rate to capecitabine, based on the presence of homozygous s/s variant of the tser. outline: this is an open-label, multicenter study. patients receive oral capecitabine twice daily on days 1-14. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. projected accrual: a total of 65 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed pancreatic cancer * stage iv disease * measurable disease (≥ 1 cm or \> 10 mm lesion(s) by spiral ct scan) * disease progression after ≥ 1 gemcitabine-based treatment regimen for advanced/metastatic disease * patient carries the double tandem repeat (s/s) variant of the thymidylate synthase gene enhancer region (tser) * no active cns metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth) patient characteristics: * ecog performance status 0-2 * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * ast/alt ≤ 2.5 times upper limit of normal (uln) (5 times uln if attributable to liver metastases) * total bilirubin ≤ 1.5 times uln * creatinine normal or creatinine clearance \> 50 ml/min * fertile patients must use effective contraception during and for 30 days after completion of study treatment * not pregnant or nursing * negative pregnancy test * asymptomatic hiv infection allowed * no recent or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, bleeding, inflammation, emesis, or diarrhea \> grade 1) * able to swallow capecitabine tablets * no known hypersensitivity to fluorouracil * no dihydropyrimidine dehydrogenase (dpd) deficiency * no clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias not well controlled with medication) * no myocardial infarction within the past 6 months * no serious, uncontrolled, concurrent infection(s) * no prior unanticipated severe reaction to fluoropyrimidine therapy * no other malignancy within the past 5 years except cured nonmelanoma skin cancer or treated carcinoma in situ of the cervix prior concurrent therapy: * see disease characteristics * at least 3 weeks since prior chemotherapy * no prior capecitabine except in the adjuvant setting * at least 3 weeks since prior radiotherapy or major surgery * at least 4 weeks since prior participation in any investigational drug study * at least 4 weeks since prior sorivudine or brivudine * no concurrent sorivudine or brivudine * no concurrent cimetidine or azidothymidine (azt) * concurrent radiotherapy for bone pain allowed to a limited field provided ≥ 1 indicator lesion remains outside of the field * no other concurrent chemotherapy or immunotherapy

Keywords: recurrent pancreatic cancer stage iv pancreatic cancer