g-csf in preventing neutropenia during first-line treatment with chemotherapy and bevacizumab in patients with metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: g-csf may prevent or control neutropenia caused by first-line therapy in patients with metastatic colorectal cancer. purpose: this phase ii trial is studying how well g-csf works in preventing neutropenia during first-line treatment with chemotherapy and bevacizumab in patients with metastatic colorectal cancer.

objectives: primary * determine if primary prophylaxis comprising filgrastim (g-csf) makes it possible to obtain neutropenia lower than grade 4 or a 30% decrease in fever in patients with metastatic colorectal cancer receiving first-line folfiri and bevacizumab and who are homozygous for allele ugt1a1\*28 (genotype 7/7), a promoter of the gene coding for enzyme ugt1a1. secondary * evaluate the objective response rate at 6 months of treatment with folfiri and bevacizumab according to recist criteria. * evaluate the toxicity (excluding neutropenia) of folfiri and bevacizumab according to nci-ctc v. 2.0. * determine progression-free and overall survival. * determine the time to treatment failure. outline: this is a multicenter study. patients receive bevacizumab iv over 30-90 minutes, irinotecan hydrochloride iv over 90 minutes, leucovorin calcium iv over 2 hours, and fluorouracil iv over 46 hours on day 1. patients also receive filgrastim (g-csf) subcutaneously on days 5-11. treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. after completion of study therapy, patients are followed every 2-3 months for up to 5 years.

Eligibility criteria:
disease characteristics: inclusion criteria: * histologically confirmed adenocarcinoma of the colon or rectum * metastatic disease * not surgically curable * homozygous for allele ugt1a1\*28, the promoter of the gene coding for ugt1a1 (genotype 7/7) * measurable and/or evaluable disease exclusion criteria: * original tumor not removed * cns metastases * secondary localized cerebral tumors patient characteristics: inclusion criteria: * who performance status 0-2 * anc ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * hemoglobin ≥ 9 g/dl * creatinine \> 1.5 mg/dl * total bilirubin ≤ 1.5 times normal * alkaline phosphatase ≤ 2.5 times normal (5 times normal if liver involvement) * not pregnant or nursing * negative pregnancy test * fertile patients of must use effective contraception exclusion criteria: * progressive gastroduodenal ulcer, prior hemorrhagic ulcer, or perforation in the past 6 months * enteropathy or chronic diarrhea * chronic inflammatory intestinal disease * intestinal obstruction * active cardiac disease including any of the following: * uncontrolled hypertension * myocardial infarction in the past 12 months * serious angina * nyha class ii-iv congestive heart failure * severe arrhythmia (even if treated) * peripheral vascular disease ≥ grade 2 * unhealed wound, ulcer, or severe bone fracture * bleeding disorder or coagulopathy * severe uncontrolled infection or medical condition * proteinuria \> 500 mg/24 hours * other malignancy within the past 5 years except basal cell skin cancer or curatively treated carcinoma in situ of the cervix * known dihydropyrimidine dehydrogenase deficiency * severe traumatic injury within the past 4 weeks prior concurrent therapy: inclusion criteria: * at least 2 weeks since prior radiotherapy exclusion criteria: * prior chemotherapy for metastatic disease except adjuvant chemotherapy completed \> 6 months ago * prior irinotecan hydrochloride or bevacizumab * major surgery or biopsy within the past 4 weeks * major surgery planned * puncture in the past week * chronic aspirin (\> 325 mg/day) or nsaids * concurrent antifungal azoles (e.g., ketoconazole, fluconazole, itraconazole) * concurrent phenytoin (as in yellow fever vaccine) * concurrent hypericum perforatum (st. john's wort) * oral or parenteral coagulant in the past 10 days and during study therapy * warfarin allowed provided inr \< 1.5

Keywords: recurrent colon cancer stage iv colon cancer recurrent rectal cancer stage iv rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum