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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.

CHICAGO-Brachytherapy devices that deliver radiation therapy directly to the lumpectomy site drastically reduce the time needed for radiotherapy after surgery for early-stage breast cancer, according to two studies presented at the 87th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA).

BETHESDA, Maryland-A long-term study to determine which of two common strategies is better for treating HIV-infected individuals was initiated in January, as 21 US centers and several Australian sites began enrolling the first 1,000 patients. Participants in the SMART trial (Strategies for Management of Anti-Retroviral Therapies) are randomized to receive immediate, aggressive antiretroviral therapy ("hit-hard-early") or no HIV drugs until CD4+ T-cell counts fall below 250 cells/µL ("go-slow").

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.

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.

NEW YORK-A photograph of a stone mansion half hidden in violet light decorates the February page of the 2002 Creative Center for Women With Cancer Novartis Desk Calendar. The photographer, Susan Markisz, writes in the calendar that "cancer, like photography, is both a positive and negative process, one that does not quite define me, but which demands interpretation."

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.

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).