ONCOLOGY Vol 16 No 3 | Oncology

Single-Agent Rituximab in Early-Stage Chronic Lymphocytic Leukemia

March 01, 2002

Currently, patients with early-stage chronic lymphocytic leukemia (CLL) without active disease are observed. However, those patients with elevated beta-2-microglobulin levels appear to have a shorter median survival (6 years vs 10+ years).

Recruitment for Trial of Adjuvant Trastuzumab Under Way

March 01, 2002

Recruitment for a challenging breast cancer trial has begun at sites in more than 40 countries. It is hoped that more than 3,000 patients from approximately 600 sites will participate in a study designed to determine whether earlier use of trastuzumab (Herceptin) increases disease-free survival in women with early breast cancer.

Successful Treatment of Pure Red Cell Aplasia With Rituximab in Patients With Chronic Lymphocytic Leukemia

March 01, 2002

Pure red cell aplasia is a rare occurrence in patients with chronic lymphocytic leukemia (CLL). This report is based on two cases-CLL patients with documented pure red cell aplasia who responded remarkably to anti-CD20 or rituximab (Rituxan

Rituximab in the Treatment of Acquired Factor VIII Inhibitors

March 01, 2002

Autoantibodies against factor VIII are rare but may cause life-threatening bleeding. Up to 30% of inhibitors may resolve spontaneously, but immunosuppressive drugs with possible serious adverse effects and costly factor replacement are usually required. Rituximab (Rituxan), a humanized monoclonal antibody against CD20-positive B cells, has been reported to be beneficial in certain antibody-mediated autoimmune diseases. We describe here four consecutively treated patients whose acquired factor VIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab administered at 375 mg/m² weekly for 2 to 4 weeks.

A Phase II Study of Apolizumab, a Humanized Monoclonal Antibody, in Patients With Relapsed or Refractory Follicular, Small Lymphocytic, or Marginal Zone/MALT B-Cell Lymphoma

March 01, 2002

The humanized monoclonal antibody apolizumab (Remitogen, Hu1D10), directed against a polymorphic determinant of HLA-DR expressed on normal and malignant B cells, is capable of inducing antibody-dependent cellular cytotoxicity, complement-mediated lysis, and direct apoptosis of lymphoma cell lines (Int J Cancer 93:556-565, 2001).

Support for New Medicare Pay Formula

March 01, 2002

The Medicare Payment Advisory Commission (MedPAC) has agreed that Medicare’s physician-fee formula needs to be overhauled. Medicare cut physician fees this year by 5.4% because of an "update" in the formula that MedPAC agreed is seriously flawed.

Phase II Trial of CHOP Followed by Rituximab, a Chimeric Monoclonal Anti-CD20 Antibody, for Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphoma: SWOG 9800

March 01, 2002

The optimal therapy for advanced-stage follicular lymphoma is unknown. Combination chemotherapy usually induces remissions in most patients; however, nearly all patients eventually progress and there is no clear plateau on disease-free survival analysis. Single-agent treatment with the monoclonal anti-CD20 antibody rituximab (Rituxan) at 375 mg/m² weekly × 4 doses induces response rates of approximately 50% to 60% in patients with relapsed follicular non-Hodgkin’s lymphoma. In some patients, the molecular detection of disease by polymerase chain reaction assay may be eliminated following antibody therapy.

A Randomized Trial of Fludarabine and Mitoxantrone Plus Rituximab vs CHOP Plus Rituximab as First-Line Treatment in Patients With Follicular Lymphoma

March 01, 2002

The FM (fludarabine [Fludara], mitoxantrone [Novantrone]) combination is an effective strategy in follicular lymphoma. From October 1999, patients from 12 Italian centers were randomized for a comparative study of FM vs CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy with the addition of rituximab (Rituxan) in selected cases.

Irinotecan-Containing Regimen Improves Survival in Small-Cell Lung Cancer

March 01, 2002

Anew treatment for small-cell lung cancer holds promise of dramatically improving survival for patients with the disease, said Dr. Alan Sandler, director of Vanderbilt-Ingram Cancer Center’s Thoracic Oncology Program, and leader of a large US study to further evaluate the treatment’s ability to prolong survival in patients with small-cell lung cancer.

Subsequent Chemotherapy Regimens Well Tolerated After Radioimmunotherapy With Ibritumomab Tiuxetan for Non-Hodgkin’s Lymphoma

March 01, 2002

Yttrium-90 ibritumomab tiuxetan (Zevalin) has been shown to be an effective and well-tolerated therapy for patients with relapsed B-cell non-Hodgkin’s lymphoma (NHL), with a response rate significantly higher than that seen with rituximab (Rituxan).

Treatment of Acquired Factor VIII Deficiency With Rituximab

March 01, 2002

At the 2000 American Society of Hematology meeting, we reported the successful treatment of a patient with acquired hemophilia using rituximab (Rituxan). This patient has required no therapy over the past year and has suffered no further hemorrhages. A June 2001 factor VIII level was 35%, and a factor VIII inhibitor level could not be analyzed due to the high level of factor VIII. Since then, three more patients with acquired factor VIII deficiency have received rituximab therapy at the University of Iowa, and are discussed below.

Phase III Trial of Virulizin for Advanced Pancreatic Cancer

March 01, 2002

Lorus Therapeutics announced recently that it has initiated a phase III trial to evaluate the macrophage activator Virulizin for the treatment of advanced pancreatic cancer. The company will present the results of this trial to the US Food and Drug Administration (FDA) in a new drug application at the completion of the study.

Rituximab May Overcome bcl-2–Associated Chemotherapy Resistance in Untreated Diffuse Large B-Cell Lymphomas

March 01, 2002

The antiapoptotic protein bcl-2 is associated with chemotherapy failure in untreated large B-cell lymphomas, and with the recently described poor-prognosis large B-cell lymphoma subtype displaying an activated B-cell genotype (Nature 403:503, 2000).

Rituximab Kills Freshly Isolated B-NHL and B-CLL More Efficiently by Complement Than by ADCC In Vitro: Role of CD20 Expression Levels and of the CD55 and CD59 Complement Inhibitors

March 01, 2002

Current evidence suggests that rituximab (Rituxan) works in vivo mainly through complement-dependent cytotoxicity (CDC) and/or antibody-dependent cellular cytotoxicity (ADCC). Here we have investigated the sensitivity of freshly isolated cells obtained from 33 B-cell chronic lymphocytic leukemia (B-CLL), 5 prolymphocytic leukemia (PLL), and 6 mantle cell leukemia (MCL) patients to be lysed by rituximab and complement in vitro.

Hematopoietic Stem Cell Transplantation in Lymphoma Patients Receiving Prior Therapy With Tositumomab/Iodine-131 Tositumomab

March 01, 2002

Tositumomab/iodine-131 tositumomab (Bexxar) is a novel active agent against CD20-positive lymphoma. There is a paucity of data examining the tolerance and outcome of hematopoietic stem cell transplantation (HSCT) for relapse after tositumomab/iodine-131 tositumomab.

Phase II Study of Rituximab Plus Fludarabine in Patients With Low-Grade Lymphoma: Final Report

March 01, 2002

Both rituximab (Rituxan) and fludarabine (Fludara) have individual antitumor activity against low-grade lymphoma (LGL). The combination of rituximab plus fludarabine has been shown to have synergistic activity against resistant lymphoma cell lines in vitro. We have recently completed a single-institution clinical trial of rituximab plus fludarabine in 40 patients with either treatment-naive or previously treated LGL.

Response to Treatment With Rituximab in a Patient With Acquired von Willebrand Disease

March 01, 2002

The patient is a 58-year-old woman (AA genotype) who was found to have a prolonged activated partial thromboplastin time (aPTT) of 65.7 seconds during a preoperative evaluation for spinal stenosis surgery and mild rectal bleeding. Her aPTT test repeatedly remained abnormally prolonged. The patient had an aPTT mixing study that did not correct immediately or at 2 hours (56.4 seconds vs control 29.7 seconds). Her bleeding time was also abnormally prolonged at 11 minutes.

Antibody-Targeted Chemotherapy Included in NCCN Oncology Practice Guidelines

March 01, 2002

Wyeth-Ayerst Laboratories announced recently that thousands of patients affected by acute myeloid leukemia (AML) may benefit from the new National Comprehensive Cancer Network (NCCN) guidelines for the appropriate treatment of AML, including the use of gemtuzumab ozogamicin (Mylotarg) in specific clinical situations. The only antibody-targeted chemotherapeutic agent approved by the US Food and Drug Administration, gemtuzumab is indicated for patients with CD33-positive AML in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. The safety and efficacy of this agent in patients with poor performance status and organ dysfunction has not been established.

A Phase II Trial of CHOP Followed by Tositumomab/Iodine-131 Tositumomab for Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphomas (SWOG 9911)

March 01, 2002

Advanced follicular lymphomas are incurable with conventional chemotherapy regimens. The Southwest Oncology Group (SWOG) investigated the safety and efficacy of a novel treatment approach by administering six cycles of standard CHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar] at 750 mg/m², doxorubicin HCl at 50 mg/m², vincristine [Oncovin] at 1.4 mg/m², and oral prednisone at 100 mg for 5 days), given at 3-week intervals, followed by radioimmunotherapy. Four weeks after completion of the last cycle of CHOP, patients with a partial (PR) or complete remission (CR) to chemotherapy underwent dosimetry with 450 mg of unlabeled tositumomab (anti-CD20) antibody and 35 mg of trace-labeled iodine-131 tositumomab (Bexxar).

bcl-2 Antisense as Monotherapy for Refractory Chronic Lymphocytic Leukemia

March 01, 2002

Wild-type bcl-2 protein is normally found within the bilaminar membrane of the mitochondrion, where it is believed to negatively regulate the release of cytochrome C into the cytoplasm after an apoptotic signal has triggered dimerization of bax protein.

The Addition of Rituximab to Combination Chemotherapy With Fludarabine, Cyclophosphamide, Mitoxantrone-Results of a Prospective Randomized Comparison by the German Low Grade Study Group

March 01, 2002

Rituximab (Rituxan) has shown high activity in relapsed follicular lymphomas when given alone, and phase II studies indicate that its addition to chemotherapy may further improve response rates substantially. Because prospective randomized studies have not been available so far, the German Low Grade Study Group (GLSG) started a multicenter national trial in patients with relapsed or refractory follicular cell lymphoma (FCL) or mantle cell lymphoma (MCL). As patients were treated for first-line therapy with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone), the FCM (fludarabine [Fludara], cyclophosphamide, mitoxantrone [Novantrone]) combination was chosen for salvage chemotherapy.

bcl-2 Antisense Induces Apoptosis and Potentiates Activity of Both Cytotoxic Chemotherapy and Rituximab in Primary Chronic Lymphocytic Leukemia Cells

March 01, 2002

Failure of treatment in chronic lymphocytic leukemia (CLL) is often characterized by increased expression of the antiapoptosis protein bcl-2. High levels of bcl-2 protein block the apoptotic death machinery at the mitochondrial level by maintaining the permeability transition pore (PTP) in the closed position.

Vinorelbine/Trastuzumab Produces Synergistic Effects in HER2-Positive Metastatic Breast Cancer

March 01, 2002

At the 24th Annual San Antonio Breast Cancer Symposium, researchers reported a 78% overall response rate in a phase II trial of vinorelbine (Navelbine) plus trastuzumab (Herceptin) in women with HER2-positive metastatic breast cancer. According to FDA-approved labeling, vinorelbine is not indicated for metastatic breast cancer.

Textbook of Medical Oncology, 2nd Edition

March 01, 2002

In this day of encyclopedic oncology texts, frequently updated online reference sites, and literature searches at the click of a button, is there a place for a basic medical oncology textbook? The second edition of the Textbook of Medical Oncology, edited by Drs. Cavalli, Hansen, and Kaye, is approximately 50% longer than the first edition, due in large part to the inclusion of newer therapeutic approaches.

Combination Monoclonal Antibody Therapy for Lymphoma: Treatment With Epratuzumab (Anti-CD22) and Rituximab (Anti-CD20) Is Well Tolerated

March 01, 2002

Epratuzumab (hLL2 [LymphoCide]), a humanized monoclonal antibody directed against the B-cell specific antigen CD22, has been demonstrated to be a safe and active monotherapy in phase I/II trials for the treatment of relapsed and refractory non-Hodgkin’s lymphoma (NHL).

Progression-Free Survival After Six Years (Median) Follow-Up of the First Clinical Trial of Rituximab/CHOP Chemoimmunotherapy

March 01, 2002

The first clinical trial of rituximab (Rituxan) in combination with CHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) was initiated in April 1994 (J Clin Oncol 17:268, 1999). This study showed the safety and efficacy of the combination in low-grade non-Hodgkin’s lymphoma (NHL) and enabled progression to phase II trials in intermediate-grade NHL (J Clin Oncol 19:389, 2001). In addition, the Groupe d’Etude des Lymphomes de l’Adulte (GELA) randomized phase III study has shown a statistically significant increase in progression-free survival for rituximab/CHOP as compared with CHOP alone (Blood 96:223a [abstract 950]).

More Money for Breast/Cervical Screening

March 01, 2002

Despite a tight proposed domestic budget for fiscal 2003, President Bush wants to increase spending on the National Breast and Cervical Cancer Early Detection Program administered by the Centers for Disease Control and Prevention (CDC).

Current Approaches to the Treatment of Well-Differentiated Thyroid Cancer

March 01, 2002

The increasing frequency of diagnosis and death of patients with follicular cell-derived carcinoma of the thyroid substantiates the need for a broad understanding of the optimal diagnostic and treatment strategies for this disease. Dr. Angelos has provided a good overview of the treatment modalities and approaches to follow-up for these patients. However, several points require additional emphasis or detail.

Treatment of Acute Myelogenous Leukemia

March 01, 2002

There have been significant advances in our understanding of the biology of acute myelogenous leukemia (AML), and to a lesser extent, in its treatment. Dr. Estey has provided an excellent overview of the current state of the clinical management of the disease. He has described both the standard therapeutic approaches, including allogeneic hematopoietic stem cell transplantation, as well as the role of investigational therapy. The present state of clinical research in AML is reviewed in some detail in the context of the broad clinical investigation of the disease at the M. D. Anderson Cancer Center. Dr. Estey makes a strong argument for the early consideration of investigational therapy, focusing on patients for whom "standard" therapy is demonstrably inadequate.

Recurrent Multicentric Glioblastoma Multiforme Responds to Thalidomide and Chemotherapy

March 01, 2002

Glioblastoma multiforme remains virtually incurable, with reported median survivals of less than 2 years with standard treatment.[1] In recent years, thalidomide (Thalomid) has shown activity in high-grade gliomas as a single agent and in combination with nitrosoureas and carboplatin (Paraplatin).[2-4] I will describe three cases in which patients with recurrent, multicentric glioblastoma responded to thalidomide plus chemotherapy after failing initial treatment with conventional radiation and chemotherapy for a single malignant glioma.

Treatment of Acute Myelogenous Leukemia

March 01, 2002

Therapeutic strategies are evolving for the treatment of patients with newly diagnosed acute myelogenous leukemia (AML), as well as for those with relapsed or refractory disease. Clinical and laboratory studies have demonstrated that AML is not a single disease, but a heterogeneous group of diseases with different clinical features and natural histories. There are variable responses to therapy depending on both the biologic characteristics of the disease and the clinical characteristics of the patient. Nevertheless, studies evaluating the outcomes of relatively large numbers of patients with newly diagnosed AML show that the majority still die of their disease.[1-3]

Management of Fatigue in the Cancer Patient

March 01, 2002

The Lesage and Portenoy article fulfills several important purposes. First, the authors remind us of the critical need to become more systematic and diligent in assessing and monitoring fatigue, a potentially debilitating symptom that is now recognized as the most common adverse effect experienced by cancer patients undergoing active treatment.[1] In the assessment of fatigue, the authors acknowledge that "the gold standard of evaluation is the patient’s self-report."

The Role of PC-SPES, Selenium, and Vitamin E in Prostate Cancer

March 01, 2002

The use of complementary and alternative medicine is a well-known phenomenon among cancer patients, and prostate cancer patients are no exception. The review article by Drs. Das and Kaplan nicely summarizes most of the data available on the use of PC-SPES, selenium, and vitamin E by prostate cancer patients. These three agents are probably the most widely used complementary approaches in prostate cancer, and they are the ones that have been studied most extensively. However, true data on efficacy, careful toxicity analyses, dose-response analysis, or pharmacokinetic analyses of these agents are extremely limited.

Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer

March 01, 2002

A number of molecularly targeted agents directed at critical pathways involved in cell survival and cell proliferation have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while diminishing acute and long-term toxic effects. Systematic evaluations of agents such as these are essential if continuing improvements in outcome are to be achieved in children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these agents in pediatric populations

Management of Fatigue in the Cancer Patient

March 01, 2002

Fatigue is the most common problem experienced by oncology patients.[1-2] In this issue of ONCOLOGY, Drs. Lesage and Portenoy present an excellent overview of the potential etiologies, assessment parameters, and treatment options for this complex, multidimensional symptom. As they note in their comprehensive review, research on this symptom, which has a significant impact on oncology patients’ ability to function and quality of life, is limited. Therefore, one is left to consider what important research questions need to be answered regarding cancer-related fatigue.

Management of Fatigue in the Cancer Patient

March 01, 2002

The article by Drs. Lesage and Portenoy is an excellent overview of current knowledge regarding the etiology, diagnosis, and treatment of fatigue in the cancer patient. Although we still have much to learn about cancer-related fatigue, noteworthy progress has been made over the past 10 years in identifying the problem, describing its consequences, establishing it as a recognized diagnostic entity, understanding its causes, and offering treatments.

Commentary on Abstracts #1535, #3354, and #3030

March 01, 2002

Increasing data suggest that rituximab may have activity in a variety of uncommon B-cell malignancies. Although earlier preliminary data suggested a high response rate in hairy cell leukemia (HCL) (Thomas et al: Blood 94:705a[abstract 3116], 1999), the complete response rate of 20% in patients who had previously failed cladribine (Leustatin) therapy reported by Nieva et al was considered disappointing (abstract #1535). A more promising approach to patients with refractory HCL is the BL-22 immunotoxin, in which anti-CD22 is linked to a Pseudomonas exotoxin (Kreitman et al: N Engl J Med 345:241-247, 2001). Of 16 patients treated on a phase I study who had failed at least one purine analog, 13 responded, including 11 complete remissions. At a median of 16 months, only three complete responders relapsed and these were successfully reinduced.

Commentary on Abstracts #3213, #3358, and #3506

March 01, 2002

Rituximab has been combined with a number of biological agents, including alpha-interferon (Davis et al: Clin Cancer Res 6:2644-2652, 2000; Kimby et al: Blood 96:577a[abstract 2479], 2000) and interleukin (IL)-12 (Ansell et al: Blood 99:67-74, 2002). The current design of combination trials is often based more on the availability of active agents than on any scientific rationale. The bcl-2 protein is overproduced in 60% to 80% or more of follicular NHL patients and in more than 80% of patients with CLL. A result is decreased apoptosis related to the prevention or slowing of activation of caspases. A resulting effect is a form of multidrug resistance. bcl-2 knockout mice have severe immunodeficiency and lymphocytopenia, suggesting that bcl-2 may be required for the viability of these cells. G3139 is an antisense bcl-2 oligonucleotide currently in clinical trials for a variety of solid tumors and hematologic malignancies.

Commentary on Abstract #2540

March 01, 2002

Several reports have focused on other interesting monoclonal antibodies under evaluation in patients with lymphoid malignancies. Apolizumab (Hu1D10) is a humanized monoclonal antibody directed at an human leukocyte antigen epitope on malignant and benign B cells. The expression is somewhat variable by disease, but cells from about 40% to 60% of patients are positive for the 1D10 antigen.

Commentary on Abstracts #1533, #1530, #3212, #1534, #3210, #2650, #3215, #1536, and #1537

March 01, 2002

The initial experience with rituximab in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) was disappointing. In the first six papers, primarily including patients with relapsed and refractory SLL, there were no complete remissions, with an overall response rate of about 12%, of brief duration (McLaughlin et al: J Clin Oncol 16:2825-2833, 1998; Maloney et al: Blood 90:2188-2195, 1997; Nguyen et al: Eur J Haematol 62:76-82, 1999; Piro et al: Ann Oncol 10:655-661, 1999; Winkler et al: Blood 94:312a [abstract 1396], 1999; Foran et al: J Clin Oncol 18:317-324, 2000).

Commentary on Abstracts #3025, #3502, #2519, and #1447

March 01, 2002

Rituximab as a single agent induces responses in about 32% of patients with aggressive B-cell NHL, although these responses tended to be partial and brief (Coiffier et al: Blood 92:1927-1932, 1998). Nevertheless, because of its favorable toxicity profile, the antibody was rapidly incorporated into combination chemotherapy regimens, most often with CHOP, the standard program for this histology. Vose and coworkers (J Clin Oncol 19:389-397, 2001) published the results of a multicenter phase II trial in which the antibody was administered on day 1 of each 21-day cycle, with CHOP beginning on day 3, in contrast to the schedule reported by Czuczman et al (J Clin Oncol 17:268-276, 1999).

Commentary on Abstracts #633 and #2523

March 01, 2002

How the monoclonal antibodies work in lymphoid malignancies remains unclear. Several studies presented at the 2001 American Society of Hematology (ASH) meeting provided insight into their mechanisms of action, and also into how cells become resistant to their effects.

Commentary on Abstracts #3504, #2526, #836, and #2533

March 01, 2002

Radioimmunotherapy is another promising area of lymphoma therapy. The two radioimmunoconjugates (RICs) that have been the most widely studied in patients with follicular, low-grade NHL are tositumomab/iodine-131 tositumomab (Bexxar) and yttrium-90 ibritumomab tiuxetan (Zevalin). Both have demonstrated a high level of activity in patients who have failed chemotherapy and rituximab (Witzig et al: J Clin Oncol 17:3793-3803, 1999; Kaminski et al: J Clin Oncol 19:3918-3928, 2001).

Commentary on Abstracts #2519, #3502, #2518, #3500, and #3507

March 01, 2002

Rituximab was approved by the US Food and Drug Administration largely on the basis of the pivotal trial conducted in 166 patients with follicular/low-grade NHL who had failed a median of two prior chemotherapy regimens (McLaughlin et al: J Clin Oncol 16:2825-2833, 1998). The response rate was 48%, including 6% complete remissions (CR), lasting a median of about a year. Attempts to improve on these results by using rituximab as initial therapy have not provided convincing evidence for improved patient outcome (Hainsworth et al: Blood 95:3052-3056, 2000; Colombat et al: Blood 97:101-106, 2001). The high response rates in the French trial by Colombat and co-workers are related in large part to the favorable nature of the patient population. Moreover, median duration of response was only about a year. In the study from Hainsworth et al mentioned above, response rates when calculated by standard methods were comparable to those seen in relapsed and refractory patients.

Commentary (Cheson): Rituximab in the Treatment of Autoimmune Hemolytic Anemia

March 01, 2002

Based on its B-cell-depleting properties, rituximab as a single agent or in combination with immunosuppressive chemotherapy drugs has been used to successfully treat nonmalignant hematologic conditions such as immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia, cold agglutinin disease, and pure red cell aplasia (Hegde et al: Proc Am Soc Clin Oncol 20:305a[abstract 1218], 2001; Perrota and Abuel: Blood 92:88b[abstract 3360, 1998; Saleh et al: Blood 96:252a[abstract 1086], 2000; Lee et al: Blood 96:596a[abstract 2560], 2000; Rai et al: Blood 96:754a[abstract 3264, 2000; Zecca et al: Blood 97:3995-3997, 2001; Stasi et al: 98:952-957, 2001), with encouraging success. Anecdotal reports also suggest activity for rituximab in systemic lupus erythematosus, rheumatoid arthritis, inflammatory arthropathy, and paraneoplastic pemphigus (Edwards and Cambridge: Rheumatology 40:205-211, 2001; Protheroe et al: Rheumatology 38:1150-1152, 1999; Heizmann et al: Am J Hematol 66:142-144, 2001).

Management of Fatigue in the Cancer Patient

March 01, 2002

Fatigue is one of the most common symptoms experienced by patients with cancer and other progressive diseases. Although reported to be a major obstacle to maintaining normal daily activities and quality of life, remarkably few studies of this syndrome have been conducted.

Treatment of Acute Myelogenous Leukemia

March 01, 2002

The treatment of patients with acute myelogenous leukemia (AML) ranges from palliative care only, to standard therapy, to investigational approaches. Acute myelogenous leukemia is, in fact, several different diseases, and the percentage of clinical responses varies with disease and prognostic subsets.

Current Approaches to the Treatment of Well-Differentiated Thyroid Cancer

March 01, 2002

The management of well-differentiated thyroid cancer requires a multidisciplinary approach. The majority of patients are diagnosed only after a nodule is palpable. A cytologic evaluation can readily diagnose a papillary thyroid carcinoma but a follicular carcinoma requires determination of capsular or vascular invasion.

The Role of PC-SPES, Selenium, and Vitamin E in Prostate Cancer

March 01, 2002

Prostate cancer patients commonly use complementary and alternative medications. There has been growing interest in recent years in the role of the herbal medication PC-SPES and the essential nutrients selenium and vitamin E in the prevention and treatment of prostate cancer. This article reviews the preclinical and clinical studies of these therapies.

Activity of Rituximab in Extranodal Marginal Zone Lymphomas (MALT Type)

March 01, 2002

This phase II study aimed to evaluate the tolerability and activity of the monoclonal anti-CD20 antibody rituximab (Rituxan) in patients with either untreated or relapsed biopsy-proven extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, with measurable or evaluable disease.

Rituximab Plus CHOP in the Treatment of Elderly Patients With Diffuse Large B-Cell Lymphoma: An Update of the GELA Study

March 01, 2002

At the 2000 Annual Meeting of the American Society of Hematology, we presented the benefits of rituximab (Rituxan) combined with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone), known as R-CHOP, in comparison with CHOP alone for the treatment of elderly patients with diffuse large B-cell lymphoma (DLCL).

Therapeutic Activity of Humanized Anti-CD20 Monoclonal Antibody and Polymorphism in IgG FcReceptor FcgRIIIa Gene

March 01, 2002

Rituximab (Rituxan) is a chimeric IgG1 anti-CD20 monoclonal antibody increasingly used in the treatment of non-Hodgkin’s lymphoma (NHL). Previous in vitro studies have suggested the role of antibody-dependent cellular cytotoxicity (ADCC) and FcgR-positive effector cells (natural killer and macrophage) in the antitumor effects of anti-CD20 antibodies, but the actual mechanism of rituximab action in vivo remains largely unknown. The FCGR3A gene coding for the FcgRIIIa receptor displays a functional dimorphism with either a phenylalanine (FCGR3A-158F) or a valine (FCGR3A-158V) at amino acid 158, with a higher affinity of human IgG1 and increased ADCC for the latter. The aim of this study was thus to determine the influence of this FCGR3A polymorphism on clinical and molecular responses to rituximab.

Cost-Effectiveness of Rituximab in Treatment of Diffuse Large B-Cell Lymphoma

March 01, 2002

Rituximab (Rituxan), when combined with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy (R-CHOP) in the treatment of patients with CD20-positive diffuse large B-cell lymphoma (DLCL), significantly prolongs event-free and overall survival (GELA [Groupe d’Etude des Lymphomes de l’Adulte] LNH 98-5 study). Our objective was to estimate the cost-effectiveness of R-CHOP based on the evidence currently available.

Monoclonal Antibodies That Mimic the Action of Intravenous Immunoglobulin Can Inhibit Immune Thrombocytopenia

March 01, 2002

Intravenous immunoglobulin (IVIG) is prepared from large pools of plasma from healthy donors and is widely used to treat autoimmune diseases, especially immune thrombocytopenic purpura (ITP). Human polyclonal antierythrocyte antibodies, such as anti-D, can also be effective at treating ITP in individuals expressing the appropriate antigen. The demand for IVIG and anti-D exceeds the supply, and the development of a recombinant product to replace these human-derived blood products would be highly desirable. We have hypothesized that monoclonal antibodies directed against red cells may be effective in inhibiting immune forms of thrombocytopenia.

FDA Approves Pegfilgrastim to Protect Against Chemotherapy-Related Neutropenia

March 01, 2002

The US Food and Drug Administration has approved Amgen’s pegfilgrastim (Neulasta) for use in decreasing the incidence of infection, as manifested by febrile neutropenia. The agent, administered in a single fixed dose per chemotherapy cycle, is indicated for patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy associated with a significant incidence of febrile neutropenia.

Rubitecan Active in Hematologic Malignancies

March 01, 2002

Data from a phase II clinical study demonstrated that the investigational oral agent rubitecan (9-nitrocamptothecin, or 9NC) is active in both chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). These data were presented at the 43rd annual meeting of the American Society of Hematology (ASH) in Orlando.

The Role of PC-SPES, Selenium, and Vitamin E in Prostate Cancer

March 01, 2002

Prostate cancer has been the most common visceral malignancy in American men for the last decade. The estimated lifetime risk of the disease in the United States is 16.6% for white men and 18.1% for African-American men, with a lifetime risk of death of 3.5% and 4.3%, respectively.[1] Recently, the National Cancer Institute (NCI) reported that the overall cancer mortality rate decreased between 1990 and 1997, including a reduction of approximately 6% in prostate cancer mortality.[1] Furthermore, Tarone et al reported that the mortality rate for prostate cancer among white men in the United States declined to a level lower than that reported prior to the introduction of prostate-specific antigen (PSA)-based screening in 1987.[2]

Current Approaches to the Treatment of Well-Differentiated Thyroid Cancer

March 01, 2002

Well-differentiated thyroid cancer is something of an anomaly in the field of oncology for two primary reasons. First, the team of physicians who manage the patient consists primarily of endocrinologists, endocrine surgeons, and nuclear medicine physicians instead of medical oncologists, surgical oncologists, and radiation oncologists. Second, there is an extremely high rate of cure with remarkable 10- and 20-year survival rates due to the indolent nature of the tumor, even in the setting of lymph node metastases.

Durable Responses Reported With Radioimmunotherapy in Low-Grade Non-Hodgkin’s Lymphoma

March 01, 2002

According to studies presented at the 43rd annual meeting of the American Society of Hematology (ASH), tositumomab/iodine-131 tositumomab (Bexxar), an investigational radioimmunotherapy being evaluated for the treatment of low-grade or transformed low-grade non-Hodgkin’s lymphoma (NHL), produced durable, long-term responses when used alone or following chemotherapy. Multiple presentations suggested that tositumomab/iodine-131 tositumomab may be an important new treatment option for patients with relapsed or refractory NHL and, in particular, for patients whose prognosis is poor.

Mantle Cell Lymphoma: High Rates of Complete Remission and Prolonged Failure-Free Survival With Rituximab/Hyper-CVAD Without Stem Cell Transplant

March 01, 2002

Previously untreated mantle cell lymphoma (MCL) is an uncommon disorder with a poor prognosis when treated with CHOP-like (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) regimens. Typically the complete remission (CR) rate is 20% to 30%, median failure-free survival (FFS) is 10 to 16 months, and median overall survival (OS) is 3 years.

Tolerance of Treatment Subsequent to Front-Line Tositumomab/Iodine-131 Tositumomab in Patients With Follicular Lymphoma

March 01, 2002

Front-line treatment for previously untreated follicular B-cell lymphoma with the iodine-131-labeled anti-CD20 antibody tositumomab (Bexxar) has been reported to result in a 97% response rate and a 74% complete response rate. Although the median duration of response has not yet been reached with a median follow-up of 2.7 years, concerns have been raised over the tolerability of salvage treatments upon relapse of disease. We have reviewed the clinical course of the 28 patients that have relapsed among the original group of 76 patients treated with tositumomab/iodine-131 tositumomab as front-line therapy.