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Ibritumomab tiuxetan (Zevalin) is a murine IgG directed against CD20 and conjugated to yttrium-90. The basic antibody is the murine rituximab. The yttrium-90 isotope was selected because it has a number of properties that are considered to be more favorable than those of iodine-131. These include the fact that ibritumomab tiuxetan is a pure beta-emitter, with higher energy and a longer path length. Ibritumomab tiuxetan has been reported to induce responses in 67% of patients with intermediate- and high-grade NHLs and 82% of those with low-grade NHL who had not been treated previously with rituximab (Witzig et al: J Clin Oncol 17:3793-3803, 1999).

Few advances in the treatment of multiple myeloma have been made in recent years, and this disease remains incurable. The observation that about 20% of plasma cells from myeloma patients express CD20 has led to some interest in studying monoclonal antibodies in this disorder. Treon et al (abstract #1398) reported the preliminary results of their phase II trial with rituximab in previously treated multiple myeloma patients. Among nine patients evaluable for response at the time of the report, there was one PR in a patient with mostly CD20-positive bone marrow plasma cells.

Although responses to rituximab occur in approximately 50% of patients with follicular NHL, several studies in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have shown response rates in the range of only 10% to 15%

One logical next step in research on rituximab was to study its activity in previously untreated patients. At the 1999 ASH meeting, Solal-Céligny et al (abstract #2802) presented the French experience with 50 patients who had low-risk follicular NHL, as defined by the following characteristics: absence of B symptoms, no tumor mass > 7 cm, and a normal LDH and serum beta-2-microglobulin. The overall response rate to rituximab was 69%, including 31% complete remissions (CRs) and 10% unconfirmed complete remissions (CRu), as defined by the international response criteria (Cheson et al: J Clin Oncol 17:1244-1253, 1999). Of considerable interest was the fact that over 50% of patients who were positive for the bcl-2 rearrangement (as determined by polymerase chain reaction [PCR] assay) prior to therapy were PCR negative after treatment. A quarter of the patients had recurred at a median of 13 months. Therefore, longer follow-up will be required to determine whether a molecular response will be associated with more durable responses and the potential for prolongation of survival.

One of the unfortunate consequences of solid organ or bone marrow transplantation is the occurrence of a post-transplant lymphoproliferative disorder (PTLD). These tumors run a variable course; some regress with a reduction in the doses of immunosuppressive agents, whereas others progress to an aggressive NHL and require systemic therapy. Chemotherapy has been relatively unsuccessful against such tumors, and the outcome is generally fatal.

Mantle cell lymphoma is one of the most challenging of the NHLs. It exhibits the worst features of both the indolent and aggressive lymphomas. With its short survival of 2 ½ to 3 years, mantle cell lymphoma resembles an aggressive NHL, but,

Leonard et al (abstract #404) described their experience with a new humanized anti-CD22 monoclonal antibody, epratuzumab. This antibody has previously been studied conjugated to both iodine-131 and yttrium-90 in the treatment of

A number of mechanisms of action for rituximab have been proposed,includingantibody-dependent cellular cytotoxicity, complement-mediated cytotoxicity, induction of apoptosis, recruitment of effector cells, and elaboration of cytokines

Unfortunately, even with the high response rates achieved by rituximab relapse is inevitable. With traditional chemotherapeutic regimens, retreatment using the same or similar agents results in lower response rates, and the duration of

Monoclonal antibody therapy has proven to be expensive, and, therefore, it is important to compare the cost-efficacy of a drug such as rituximab with other standard therapies for low-grade lymphoma. Two abstracts presented at the 1998 ASH

At the 1999 ASH meeting, Vose et al (abstract #387) analyzed the overall multicenter experience with iodine-131 tositumomab in 179 patients as a function of histologic subtype. The overall response rate was 81%, with 39% CRs . The median time to progression for responders was 13 months, with a median duration of response of 11 months, although the median duration of CRs was 57 months. The response rates for the follicular small cleaved cell NHL and follicular mixed (follicular grades I and II) were similar (83% and 78%, respectively), as were the CR rates (38% and 39%, respectively). These histologies have shown similar responses to various chemotherapy regimens in most studies.

Since hepatocellular carcinoma almost always develops in patients with underlying hepatitis or cirrhosis of the liver, it cannot be viewed as a single disease. Not only does the biology of the cancer vary depending on the underlying etiology of the liver disease-hepatitis B, hepatitis C, or cirrhosis of another etiology-but also patient outcomes are determined by the interplay between tumor growth and

Iodine-131 tositumomab (Bexxar) is a new radioimmunotherapy in development for the treatment of patients with low-grade or transformed low-grade non-Hodgkin’s lymphoma. The data from five phase I-III studies, which enrolled patients with low-

Tositumomab and iodine -131 tositumomab (Bexxar) is a new radioimmunotherapy in development for the treatment of low-grade or transformed, low-grade non-Hodgkin’s lymphoma (NHL).

PITTSBURGH-Adjuvant therapy in patients with small, node-negative breast tumors has been controversial due to the lack of randomized studies. To explore this question, University of Pittsburgh researchers reviewed data on patients with tumors of 1 cm or less from five large clinical trials of adjuvant therapy that enrolled women with various-sized tumors.

Strength for Caring is a community-based educational program led by trained nurses or social workers who teach caregivers about the skills and resources they need to care for a loved one with cancer.

HOUSTON-The treatment of relapsed or refractory non-Hodgkin’s lymphoma has clearly been improved by the monoclonal antibody, rituximab (Rituxan). Because of encouraging results in this setting, rituximab is being studied in previously treated patients with chronic lymphocytic leukemia (CLL), where it is showing significant activity as well, according to a presentation at ASH by M. D. Anderson investigators.

BETHESDA, Md-The National Institutes of Health has proposed a set of guidelines aimed at ensuring the ethical and legal conduct of any embryonic and fetal stem cell research that it funds.

ROCKVILLE, Md—An old agency has a new name. On orders from Congress, the Agency for Health Care Policy and Research (AHCPR) is now the Agency for Healthcare Research and Quality (AHRQ), pronounced “arc.”

PHILADELPHIA—SmithKline Beecham has announced that labeling for Engerix-B (hepatitis B vaccine recombinant) now includes a statement recognizing the hepatitis B vaccine as “the first anti-cancer vaccine because it can prevent primary liver cancer. A clear link has been demonstrated between chronic hepatitis B infection and the occurrence of hepatocellular carcinoma.”

Better Symmetry With Tissue Reconstruction vs Implants

WASHINGTON-President Clinton will ask Congress to appropriate an additional $100 million to battle AIDS outside the United States in his budget request for fiscal year 2001. This would raise to $325 million the amount of funding pledged by the United States that year to help foreign nations prevent and treat the disease.

ROCKVILLE, Md-The monoclonal antibody rituximab (Rituxan), which is directed against the CD20 antigen expressed in most B-cell malignancies, can be given repeatedly to patients with non-Hodgkin’s lymphoma (NHL) and may produce longer responses with retreatment. This unusual increase in response duration is in contrast to the ever-diminishing efficacy seen with repeated rounds of chemotherapy, researchers reported at the 41st annual meeting of the American Society of Hematology (ASH).

WASHINGTON-The American Federation of Clinical Oncologic Societies (AFCOS) has developed a 15-item list of basic standards for consumers to consider in selecting a health insurance plan. The aim is to ensure that patients will obtain high-quality cancer care, should they need it. AFCOS, a coalition of nine professional medical societies, released the list at a Capitol Hill briefing sponsored by Rep. Sue Kelly (R-NY) and Rep. Anna Eshoo (D-CA).

The National Cancer Institute has compressed 45 years of cancer mortality data into a single atlas. The new publication contains 254 color-coded maps showing variations in cancer deaths over two time periods, across various

BUFFALO, New York-Gerald P. Murphy, MD, DSc, seventh director of Roswell Park Cancer Institute (RPCI), died suddenly, January 21, 2000, in Tel Aviv, Israel, while attending an International Union Against Cancer meeting in his role as secretary-general. Dr. Murphy was 65. He began his career at RPCI in 1967 when he was appointed associate director for clinical affairs and chief of the Departments of Urology and Experimental Surgery. He served as director of RPCI from 1970 to 1985.

SEATTLE-A phase III study of 168 patients with hematologic malignancies found that those receiving peripheral blood stem cells (PBSC) had fewer relapses, fewer deaths, and faster engraftment than those receiving bone marrow, without a greater risk of acute graft-vs-host disease (GVHD). Both the PBSC and bone marrow transplants were from HLA identical sibling donors. William Bensinger, MD, a researcher in the Clinical Research Division at the Fred Hutchinson Cancer Research Center reported the study at the ASH meeting.

BETHESDA, Md-The National Cancer Institute (NCI) plans to increase both the number of research grants it awards in fiscal year 2000 and the size of the average grant, but it also expects to fund a smaller percentage of grant requests because of the increasing number of proposals it is receiving.

WASHINGTON-Rep. Rick Lazio (R-NY) is a vocal advocate within Congress for cancer research and cancer patients. The fourth-term representative from Long Island is founder of the House Cancer Awareness Working Group. He has been a leader in efforts to increase the National Cancer Institute (NCI) budget and has sponsored or co-sponsored major pieces of cancer legislation.

BETHESDA, Md-J. Paul Van Nevel ended a 26-year career at the National Cancer Institute on Dec. 31, when he retired as associate director for cancer communications. He immediately began a new career as a communications consultant, with NCI as a client.