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THOUSAND OAKS, California-The US Food and Drug Administration has approved Amgen’s Neulasta (pegfilgrastim), its pegylated granulocyte colony-stimulating factor (G-CSF) that is administered as a single fixed dose per chemotherapy cycle, the company said in a news release. Neulasta is indicated for decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

MONTREAL-Delirium in patients with advanced cancer appeared to be associated with changes in the circadian distribution of analgesia for breakthrough pain and may be due to a reversal of the normal circadian rhythm in these patients, reported Bruno Gagnon, MD, of McGill University and Montreal General Hospital.

BETHESDA, Maryland-The new director of the National Cancer Institute intends to advance NCI’s role in the discovery and application of specific targets for diagnosing and treating cancer, and to increase its interaction with other organizations to more fully integrate and coordinate cancer research and care.

In this report, we present our results of the biochemotherapy combination of rituximab (Rituxan), a monoclonal antibody against CD20, with fludarabine (Fludara) and cyclophosphamide (Cytoxan, Neosar).

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).

Monoclonal antibodies demonstrate impressive response rates in lymphoid diseases, and treatment indications are expanding. Both alemtuzumab (Campath) (anti-CD52) and rituximab (Rituxan) (anti-CD20) are active in chronic lymphocytic leukemia (CLL) and low-grade lymphomas.

SAN DIEGO--Recognizing the stress associated with oncology nursing care, the Regional Cancer Center of Faxton-St. Luke’s Healthcare, Utica, NY, initiated a novel 6-week staff wellness pilot project, dubbed "The Take a Break Club." Karen Miller, RN, OCN, the Center’s cancer program education coordinator, described the program and its benefits in her podium presentation at the 26th Annual Conference of the Oncology Nursing Society (abstract 31). "We all know there is a nursing shortage, and so you can’t forget staff satisfaction," Ms. Miller said. "That’s what I’m looking to accomplish with this particular project."

SAN DIEGO-A multidisciplinary group of nurses at New York’s Memorial Sloan-Kettering Cancer Center have developed a standard of care for cancer patients suffering from decreased quality of life due to constipation.

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]).

WASHINGTON-Advocacy groups have played a significant role in the thus-far successful effort to double the National Institutes of Health budget and will continue to wield important influence in promoting federal funding for biomedical research, a panel of experts agreed during a media forum.

ORLANDO-Adding rituximab (Rituxan) to paclitaxel (Taxol)/topotecan (Hycamtin) salvage therapy raises response rates by about 25%, more than triples complete response rates, and is effective in both primary refractory and relapsed aggressive B-cell lymphomas.

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."

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

A 51-year-old man presents with iron deficiency anemia and occasional blood in his stool. He has no abdominal pain, no change in appetite, no diarrhea or constipation, no melena, and no loss of weight. The patient denies any nausea and vomiting.

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.

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.

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.

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.

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.

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).

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).

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.

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).

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.

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).

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.

This phase II trial investigated the safety and efficacy of a combined-modality treatment with rituximab (Rituxan) and fludarabine (Fludara) in patients with fludarabine- and anthracycline-naive chronic lymphocytic lymphoma (CLL).

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.

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.

ROCKVILLE, Maryland-The Food and Drug Administration (FDA) has approved the use of Gleevec (imatinib mesylate, Novartis) for the treatment of c-kit-positive inoperable and metastatic malignant gastrointestinal stromal tumors (GISTs).