A Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Advanced Small Bowel Adenocarcinoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically* or cytologically* confirmed small bowel adenocarcinoma

- Metastatic or unresectable locally advanced disease NOTE: *Biopsy may be of
primary tumor or from a metastatic site if there is a primary small bowel tumor
or currently or previously present.

- Measurable disease

- For patients with lesions ≥ 1 cm but < 2 cm, spiral CT scan imaging must be used
for tumor assessments

- Confirmed UGT1A1 TA indel genotype of 6/6, 6/7, or 7/7

- No periampullary carcinoma or appendiceal cancer

- No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is
present)

- Bilirubin normal for patients with 6/6 genotype (< 2 times ULN for patients with 6/7
or 7/7 genotype)

- Hemoglobin ≥ 9.0 g/dL

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active or uncontrolled infection

- No other concurrent malignancy, except for nonmelanoma skin cancer

- No preexisting sensory neuropathy ≥ grade 2

- No evidence of serious intercurrent illness, including any of the following:

- Unstable angina

- Symptomatic congestive heart failure

- Serious uncontrolled cardiac arrhythmia

PRIOR CONCURRENT THERAPY:

- At least 2 weeks since prior radiotherapy

- At least 4 weeks since prior major surgery

- No prior chemotherapy for advanced small bowel cancer

- Prior adjuvant fluorouracil/leucovorin calcium allowed provided last dose was ≥
3 months ago

- No prior adjuvant oxaliplatin or irinotecan hydrochloride

- No prior radiotherapy to > 25% of bone marrow

- No concurrent sorivudine, brivudine, lamivudine, or stavudine

- No concurrent sargramostim (GM-CSF) or pegfilgrastim