A Phase II Study of Docetaxel, Cisplatin and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed gastric or esophageal adenocarcinoma
- Gastroesophageal junction adenocarcinoma classified according to Siewert's class
type I-III allowed
- Locally recurrent, metastatic, or unresectable disease
- If recurrent or metastatic disease is not histologically confirmed, then
documentation by a second radiographic procedure (i.e., positron emission
tomography scan or MRI in addition to CT scan) is required
- If the imaging procedure does not confirm recurrent or metastatic disease,
biopsy confirmation is required
- Measurable or nonmeasurable disease that can be radiographically evaluated
- Measurable disease is defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm
by conventional techniques OR ≥ 10 mm by high-resolution imaging
- Nonmeasurable disease is defined as disease that can be identified on radiology
studies, but does not meet the criteria for measurable disease
- No brain or CNS metastases, including leptomeningeal disease
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9.0 g/dL
- Bilirubin normal
- Creatinine ≤ 1.5 mg/dL
- Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria:
- AP normal AND AST and ALT ≤ 5 times upper limit of normal (ULN)
- AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN
- AP ≤ 5 times ULN AND AST and ALT normal
- Urinalysis < 2+ proteinuria
- Urine protein/urine creatinine ratio < 1.0
- PT (INR) ≤ 1.5 and PTT ≤ 3 seconds above ULN (if patient not on anticoagulation)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment
- No peripheral neuropathy > grade 1
- No other neoplastic disease within the past 3 years, except basal cell carcinoma of
the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer
- No significant traumatic injury within the past 28 days
- No abdominal fistula, gastrointestinal bleeding, or intraabdominal abscess within the
past 6 months
- No serious, nonhealing wound, ulcer, or bone fracture
- Blood pressure ≤ 150/100 mm Hg
- No significant cardiac disease, including any of the following:
- Unstable angina
- New York Heart Association class II-IV heart disease
- Congestive heart failure
- Myocardial infarction within the past 6 months
- No stroke or cerebrovascular accident within the past 6 months
- No clinically significant peripheral vascular disease
- No clinically significant hearing loss or ringing in the ears
- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80
- No other medical condition or reason that, in the opinion of the investigator, would
preclude study participation
PRIOR CONCURRENT THERAPY:
- Recovered from prior therapy
- No prior chemotherapy for metastatic or unresectable disease
- No prior docetaxel, cisplatin, bevacizumab, or any other novel biologic
antiangiogenic agent
- More than 6 months since prior fluorouracil
- More than 6 months since prior adjuvant therapy (including chemotherapy and/or
chemoradiotherapy)
- More than 7 days since prior minor surgery, including fine-needle aspiration, core
biopsy, laparoscopy, or mediport placement
- More than 28 days since prior major surgery or open biopsy
- No concurrent major surgery
- No other concurrent chemotherapy or anticancer therapy
- No concurrent immunotherapy or radiotherapy
- Concurrent full-dose anticoagulants allowed if the following criteria are met:
- In-range INR (usually 2-3) on a stable dose of warfarin or low molecular weight
heparin
- No active bleeding or pathological condition that carries a high risk of
bleeding (e.g., tumor involving major vessels or known varices)