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BETHESDA, Md-Seeking better mice for research, the National Cancer Institute has funded the Mouse Models of Human Cancer Consortium, which will consist of 19 new research groups involving investigators at 30 US institutions. The teams will seek to create models that duplicate the ways human cancers develop, progress, and respond to therapies or preventive agents.

Anti–B-cell monoclonal antibodies have been proven effective in B-cell post-transplant lymphoproliferative diseases (PTLDs; Benkerrou et al: Blood 92,3137, 1998). Other treatments, such as chemotherapy or antiviral drugs, are toxic or

Hepatocellular carcinoma is a major public health problem worldwide, although at present it remains a relatively uncommon cancer in the United States. As pointed out by Dr. Venook in his elegant review of the topic, most hepatocellular carcinomas progress locoregionally. Hepatic failure is the most common mode of death for patients with this disease. For this reason, regional management strategies would appear to be attractive. Dr. Venook is to be commended for an accurate review of the literature regarding this issue. Unfortunately, that literature suffers from many limitations.

Drs. Lee and Levine have written a thoughtful, thorough review of the management of venous thromboembolism in cancer patients. Venous thromboembolism remains an important, common, and potentially fatal complication of cancer and many of its therapies. Certainly, the incidence of upper extremity and catheter-related thrombosis has increased significantly in recent years with the widespread use of central venous catheters. On the other hand, recent years have also brought new, less invasive methods of diagnosis and the promise of still more new diagnostic methods to come.

When one considers the frequency with which practicing oncologists encounter situations and issues involving venous thrombosis in their patients, it is remarkable how little attention has been paid to this problem in the oncology literature or standard textbooks of oncologic theory and practice. Although the topic of hypercoagulability in cancer patients has been the subject of several excellent articles,[1,2] these reviews, while exhaustive with respect to pathophysiology, provide relatively little information of practical use to the oncologist.

In his review, Dr. Venook correctly argues that, in the majority of pa;tients, hepatocellular carcinoma results from underlying liver disease; the most common culprit is cirrhosis, which, in turn, is frequently related to hepatitis B and/or hepatitis C exposure and alcohol abuse. Given that patient outcomes are determined by the “interplay between tumor growth and adequate hepatic reserve,” and that most patients with hepatocellular carcinoma eventually die of liver failure, Dr. Venook argues that there is a good rationale for locoregional tumor control of hepatocellular carcinoma. Locoregional therapies may include hepatic intraarterial (HIA) chemotherapy, transarterial chemoembolization, Lipiodol chemo-embolization, radiation therapy (conformal external radiation therapy or intraarterially delivered radiation), or ablative procedures. These therapies are less aggressive than conventional resectional therapies, such as cryosurg-ery, percutaneous ethanol injection, radiofrequency ablation, and other intratumoral therapies.

The growing quantity of clinical research data has created a need to find ways to effectively provide an overview of information that addresses specific medical questions. Meta-analysis is being used ever more frequently for this purpose. Therefore, it is important to recognize both the strengths and weaknesses of this analytical methodology.

In general, results with autologous stem-cell transplantation for patients with follicular NHL have been disappointing, without the evidence for cure observed in patients with large B-cell NHL (Rohatiner et al: J Clin Oncol 12:1177-1184, 1994;

Hairy cell leukemia is one of the success stories of hematologic oncology. The purine analogs cladribine (Leustatin) and pentostatin (Nipent) are similarly active, with responses in more than 90% of patients, including 65% to 85% CRs

Rituximab is generally well tolerated, with toxicities that tend not to overlap with those resulting from chemotherapy. Moreover, in vitro data suggest that monoclonal antibodies may sensitize lymphoma cells to the effects of chemotherapeutic

Campath-1H is an unconjugated, humanized monoclonal antibody directed against the CD52 antigen present on B cells, as well as T cells and other mononuclear cells. In phase II trials, this antibody has shown impressive activity in chronic lymphocytic leukemia (CLL) and T-cell prolymphocytic leukemia (T-PLL) but limited activity in NHL (Österborg et al: J Clin Oncol 15:1567-1574, 1997; Pawson et al: J Clin Oncol 15:2667-2672, 1997; Lundin et al: J Clin Oncol 16:3257-3263, 1998). In CLL, responses to Campath-1H have been reported in 30% to 70% of patients who had not responded to prior treatment, including fludarabine (Fludara), with complete response (CR) rates ranging from 4% to 50%. More than two-thirds of T-PLL patients have achieved CRs, but these do not seem to be durable. Only 14% of patients with low-grade NHL achieved partial responses (PRs), although responses were noted in about half of a small number of patients with mycosis fungoides.

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.”