BioOncology Watch

Timely Information for Practicing Physicians

 

February 2003

 

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Fludarabine with concurrent or sequential rituximab.  John Byrd and associates conducted a phase II study of 104 previously untreated patients with B-cell CLL who were randomized to receive fludarabine (25 mg/m2 daily on Days 1-5 every 28 days for 6 cycles) plus rituximab (375 mg/m2 on Days 1 and 4 of Cycle 1 and Day 1 of Cycles 2-6) followed by 4 weekly doses of rituximab (375 mg/m2) after 2 months of observation (concurrent group) or single-agent fludarabine for 6 monthly cycles followed by 4 weekly doses of rituximab after 2 months of observation (sequential group).  The concurrent group achieved a response rate of 90% (47% CRs and 43% PRs) while patients in the sequential group had a response rate of 77% (28% CRs and 49% PRs).  With a median follow-up of 23 months, the estimated 2-year progression-free survival rate was 70% in both treatment groups and the median duration of survival had not been reached for either regimen.  Toxicities were similar in both groups except that grade 3 or 4 neutropenia occurred more frequently in the concurrent group (74% vs. 41%).  Although the CR rate was greater in the concurrent group, these early phase II results have not yet demonstrated either a progression-free or an overall survival advantage for concurrent therapy compared to sequential therapy.  Phase III studies of fludarabine and rituximab treatments for CLL patients are warranted. (Byrd JC, et al. Blood 2003;101:6-14)

 

BREAST CANCER

Trastuzumab combined with taxanes.  John Merlin et al studied trastuzumab with either paclitaxel or docetaxel in HER2-positive breast cancer cell lines (MCF-7, MDA-MB453, and SK-BR3).  Additive or synergistic cytotoxic effects were observed when either taxane was combined with trastuzumab and added to cultures of these cell lines.  These experimental results warrant clinical study of trastuzumab plus taxane therapy in patients with HER2-positive breast cancer.  (Merlin J-L, et al. Ann Oncol 2002; 13:1743-1748)

 

MALIGNANT LYMPHOMA

Rituximab for central nervous system (CNS) lymphomas.  While CD20+ non-Hodgkin lymphomas are the most common subclass of lymphomas that invade the CNS, only sub-therapeutic levels of rituximab are detected in the cerebrospinal fluid after IV infusion of rituximab. James Rubenstein et al studied intrathecal administration of rituximab in cynomolgus monkeys and found that intrathecal rituximab was well tolerated and resulted in high concentrations of rituximab in the CSF.  These experiments warrant clinical studies of intrathecal rituximab therapy for patients with CNS lymphoma.  (Rubenstein JL, et al. Blood 2003;101: 466-468)

 

Rituximab for relapsed Hodgkin's disease.  Ute Rehwald and colleagues treated 14 patients with relapsed CD20+ Hodgkin’s lymphoma with 4 weekly infusions of rituximab 375 mg/m2.  Therapy was well tolerated and 12 patients (86%) achieved a response (8 CRs and 4 PRs).  Nine responding patients remained progression-free with a median follow-up of 12 months.  These early results indicate that rituximab is active against relapsed CD20+ Hodgkin’s lymphoma.  (Rehwald U, et al. Blood 2003;101:420-424)

 

MULTIPLE MYELOMA (MM)

Thalidomide alone or with dexamethasone.  Donna Weber and coworkers studied thalidomide with or without dexamethasone for the treatment of 2 cohorts of MM patients.  The first consisted of 28 patients with previously untreated asymptomatic MM who received single-agent oral thalidomide (maximum daily dose of 600 mg).  The second consisted of 40 previously untreated patients with symptomatic MM who received thalidomide (maximum daily dose of 400 mg) plus oral dexamethasone (20 mg/m2 for 4 days beginning on Days 1, 9, and 17 every 4-5 weeks).  Both groups were treated for at least 3 months. The response rate (³ 75% reduction of monoclonal protein) was 36% (n = 10) for patients treated with single-agent thalidomide and 72% (n = 29) for patients treated with thalidomide plus dexamethasone.  Five patients (16%) treated with combination therapy achieved a CR.  Grade 3 toxicities included infection (9 patients) and thromboembolic events (7 patients; 6 [15%] in the combination group and 1 [4%] in the thalidomide-alone group).  Single-agent thalidomide was effective therapy for patients with newly diagnosed MM and thalidomide plus dexamethasone induced a high rate of response with a rapid onset of remission in previously untreated patients with symptomatic MM.  (Weber D, et al. J Clin Oncol 2003;21:16-19)

 

COLORECTAL CANCER

Bevacizumab plus fluorouracil (FU)/leucovorin (LV).  Fairooz Kabbinavar et al conducted a phase II trial of 104 previously untreated patients with metastatic colorectal cancer who received either FU (500 mg/m2)/LV (500 mg/m2) IV weekly for 6 weeks every 8 weeks, bevacizumab (5 mg/kg IV every 2 weeks) plus FU/LV, or bevacizumab (10 mg/kg IV every 2 weeks) plus FU/LV.  Bevacizumab added to FU/LV increased tumor response rate (control arm, 17%; low-dose arm, 40% [p = 0.029]; high-dose arm, 24% [p = 0.434]), time to disease progression (control arm, 5.2 months; low-dose arm, 9.0 months [p = 0.005]; high-dose arm, 7.2 months [p = 0.217]), and duration of survival (control arm, 13.8 months [95% CI: 9.1-23.0 months]; low-dose arm, 21.5 months [95% CI: 17.3-undetermined months]; high-dose arm, 16.1 months [95% CI: 11.0-20.7 months]).  Versus control, more bevacizumab-treated patients had thrombotic events (19% vs. 9%), epistaxis (49% vs.11%), and hypertension (19% vs. 3%).  Further study of bevacizumab with chemotherapy for metastatic colorectal cancer is warranted.  (Kabbinavar F, et al. J Clin Oncol 2003;21:60-65) 

 

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