Intensified 1st Cycle Rituximab Plus 8th Cycles of R-CHOP Chemotherapy in Patients With Advanced or Bulky CD20+ Diffuse Large B-cell Lymphoma (DLBCL)

Inclusion criteria

• Histologically confirmed CD20 positive Diffuse Large B-cell Lymphoma (DLBCL)
• Advanced stage: stage III, IV and/or bulky disease (largest diameter ≥ 10.0 cm) regardless of stage
• Previously untreated.
• Performance status: ECOG 0-2.
• Age ≥ 18
• At least one or more bidimensionally measurable lesion(s)

• ≥ 2 cm by conventional CT
• ≥ 1 cm by spiral CT
• skin lesion (photographs should be taken) ≥ 2 cm
• measurable lesion by physical examination ≥ 2 cm
• Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormalities
• Adequate renal function: serum creatinine level < 2 mg/dL (177 μmol/L)
• Adequate liver functions:

• Transaminase (AST/ALT) < 3 X upper normal value (or < 5 x ULN in the presence of DLBCL involvement of the liver)
• Bilirubin < 2 X upper normal value (or < 5 x ULN in the presence of DLBCL involvement of the liver)
• Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone marrow involvement by lymphoma
• Life expectancy ≥ 6 months
• A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause.
• Informed consent

Exclusion criteria

• Other subtypes NHL than DLBCL
• Patients who transformed follicular lymphoma or other indolent lymphoma
• Primary Central Nervous System (CNS) DLBCL;
• CNS involvement by lymphoma or any evidence of spinal cord compression. Brain CT/MRI is only mandatory (within 4 weeks) in case of clinical suspicion of CNS involvement by lymphoma. Patients who have only had prophylactic intrathecal chemotherapy against CNS disease are eligible.
• Patients with a known history of HIV seropositivity or HCV (+). Patients who have HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period.
• Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions

• Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry
• History of significant neurological or psychiatric disorders including dementia or seizures
• Active uncontrolled infection (viral, bacterial or fungal infection)
• Other serious medical illnesses
• Known hypersensitivity to any of the study drugs or its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies)
• Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.