ONCOLOGY Table Of Contents

Mucosa-associated lymphoid tissue (MALT) lymphomas account for only 5% of NHLs, and yet they represent the most common low-grade lymphoma involving the stomach. Gastric MALT lymphomas tend to occur in association with

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.

In 1998, a retrospective cost-minimization
analysis from the perspective of a British hospital was performed
comparing the use of cyclophosphamide, doxorubicin, Oncovin, and
prednisolone (CHOP), fludarabine (FLU [Fludara]), and rituximab

At the recent annual meeting of the Society of Gynecologic Oncologists (SGO), researchers announced findings suggesting that the putative tumor-suppressor gene—the fragile histidine triad (FHIT) gene—may be central to the development of

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;

Many readers may find the article by Ost on photodynamic therapy (PDT) for lung cancer to be their introduction to this novel modality. If, for no other reason than this, the article is valuable. For those who address cancer as a systemic problem, first and foremost, the article may offer little to whet the appetite. On the other hand, the review may tempt the intellectual palates of those of us who focus our efforts on solving the sour problems of local cancers, their control, and the cost of aggressive therapies.

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.

This phase II trial investigated the safety and efficacy of retreatment with rituximab (Rituxan) in patients with low-grade or follicular non-Hodgkin’s lymphoma who relapsed following a response to rituximab therapy.

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).

Ibritumomab tiuxetan (IDEC-Y2B8 [Zevalin]) is an anti-CD20 murine immunoglobulin G1 (IgG1) kappa monoclonal antibody conjugated to tiuxetan (MXDTPA), which can securely chelate either indium-111 (111In) for imaging/dosimetry or yttrium-90 (90Y) for therapy.

When Janet Woodcock, MD, a top FDA official, appeared before a Senate committee in early February, she tried to put the issue of medical errors in perspective by referring to a patient who dies after chemotherapy. She rhetorically asked whether

Researchers in Germany and Austria have found a way to achieve high survival rates in children with Hodgkin’s disease while reducing serious long-term side effects. Until now, children with Hodgkin’s disease have experienced high survival rates but

A study released at the recent annual meeting of the Society of Gynecologic Oncologists (SGO) challenges the traditional management of ovarian cancer in young women by suggesting that conservative surgery (which often allows for future

Randomized trials are defining the role of autologous stem-cell transplantation in aggressive non-Hodgkin’s lymphoma (NHL), but there is less experience with this treatment in follicular lymphomas. Approximately 40% to 50% of patients with follicular NHL are in remission 4 to 5 years following autologous stem-cell transplantation. Results from phase II studies and retrospective analyses are remarkably similar, despite differences in patient populations, preparative regimens, use of purging, and source of stem cells. Nevertheless, there is little evidence of a plateau in disease-free survival curves, and we do not know whether patients are cured or overall survival is prolonged. Relapses 9 years following transplantation have been described.[1]

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.

Freedman et al provide an extensive overview of the literature on
high-dose therapy and transplantation in follicular non-Hodgkin’s

Transformation of low-grade non-Hodgkin’s lymphoma (NHL) to a more aggressive histology is associated with a very poor response to chemotherapy and shortened survival. Therefore, new therapeutic agents are needed. Tositumomab/iodine-

Research presented recently at the Society of Gynecologic Oncologists (SGO) annual meeting found that survival rates of African-American women with advanced-stage endometrial cancers are significantly worse than those of Caucasian women.

Rituximab (Rituxan) is a chimeric monoclonal antibody binding to CD20. A multicenter trial in relapsed low-grade lymphoma (375 mg/m²/wk × 4) produced a response rate of 48%. However, patients with small lymphocytic lymphoma

Rituximab (Rituxan) has mechanisms of
antilymphoma action that differ significantly from those of
chemotherapeutic agents: both direct (induction of apoptosis and
chemosensitization) and indirect (complement-dependent cytotoxicity
and antibody

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.

Due to the growing problem of antibiotic resistance, physicians have been clamoring for new drug companies to ratchet up antibiotic research and development. Congress had the same concern when it passed the FDA Modernization Act in 1997,

Photodynamic therapy (PDT) involves the use of photosensitizing agents that are selectively retained within tumor cells. The agents remain inactive until exposed to light of the proper wavelength. When activated by light, these

The rationale for combining rituximab
(Rituxan), a chimeric anti-CD20 monoclonal antibody, with
chemotherapy includes single-agent efficacy, non–cross-resistant
mechanisms of action, possible synergy, and few overlapping
toxicities. The safety

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%

Results from the compassionate use program for linezolid (Zyvox), an investigational new antibiotic still under development, show that the drug is effective in the treatment of patients with bacteremia associated with significant gram-positive infections,

Ibritumomab tiuxetan (IDEC-Y2B8 [Zevalin]) is
an anti-CD20 murine immunoglobulin G₁ (IgG₁)
kappa monoclonal antibody conjugated to tiuxetan that can securely
chelate either indium-111 (¹¹¹In) for imaging/dosimetry or
yttrium-90 (⁹⁰Y) for

Avax Technologies, Inc., has released 9-year follow-up data of stage III melanoma patients from company-sponsored phase II studies of M-Vax, an individualized cell-based vaccine for cancer. Ernest W. Yankee, PhD, the company’s executive vice-president, presented the data at the 26th annual meeting of the Clinical Oncological Society of Australia in Melbourne.

An Arkansas Cancer Research Center study,
published in the November 18, 1999, issue of The New England
Journal of Medicine, found that thalidomide (Thalidomid)
effectively reduced or, in some cases, eliminated tumor activity in
multiple myeloma patients who had not responded previously to other agents.

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 (MCL) is a recently identified, aggressive, B-cell neoplasm that is incurable with current combination chemotherapy regimens. Novel therapeutic strategies are needed. MCLs express high levels of cell-surface CD20 and are

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-

Venous thromboembolism is a common complication in patients with cancer. The management of deep-vein thrombosis and pulmonary embolism can be a considerable challenge in these patients. Diagnosing venous

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

Autologous peripheral blood stem-cell (PBSC) transplantation may play an important role in the treatment of indolent lymphomas, as well as aggressive lymphomas. Concern about the contamination of the autologous graft with lymphoma

There is no formula for telling a patient that he or she has cancer. The diagnosis is still perceived, for the most part, as a death sentence, and a patient’s reaction is usually a combination of fear, despair, and anger. How a physician

Most patients with advanced-stage follicular non-Hodgkin’s lymphoma (NHL) are not cured with conventional therapy. The use of high-dose therapy and autologous stem-cell transplantation in patients with relapsed follicular

Rituximab (Rituxan) may be an ideal agent for
combination with chemotherapy in patients with extensive indolent
lymphoma because of non–cross-resistant efficacy and
differential toxicity. However, lethal complications have occurred.
Furthermore

Epratuzumab is a humanized anti-CD22 monoclonal
antibody immunoglobulin G₁ (hLL2 [LymphoCide]) that has
been studied in radiolabeled forms (iodine-131[¹³¹I] and
yttrium-90 [90Y]) in the treatment of chemotherapy-refractory

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

Childhood Leukemias is a comprehensive text that encompasses every aspect of leukemia in children, ranging from general diagnosis, classification, and pathobiology to management and supportive care.

Campath-1H is a humanized anti-CD52 monoclonal antibody, which has demonstrated marked activity against advanced, refractory CLL. This multicenter phase II clinical trial sought to establish the level of activity against CLL patients exposed to

We previously reported that “in vivo purging” with rituximab (Rituxan) during stem-cell collection is safe and does not adversely affect engraftment. We now report on our transplant experience with rituximab. From June 1998 to December

Tositumomab/iodine-131 tositumomab (Bexxar) is a new
radioimmunotherapy for relapsed and refractory low-grade and
transformed low-grade non-Hodgkin’s lymphoma (NHL). Iodine-131
tositumomab is a radiolabeled murine immunoglobulin

Rituximab (Rituxan) has significant activity in low-grade non-Hodgkin’s lymphoma (NHL), but lower responses were noted in small lymphocytic lymphoma (SLL), a nodal variant of chronic lymphocytic leukemia (CLL). Pharmacokinetic data

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.

Meta-analysis is a systematic, quantitative approach to the combination of data from several clinical trials that address the same question. This analytic approach can help resolve questions that remain unclear from the results

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

B cells, plasma cells, or both may act as clonogenic cells in multiple myeloma. Circulating CD20-positive B cells bearing identical immunoglobulin H (IgH) rearrangements as autologous plasma cells circulate in most multiple myeloma patients. In

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

A total of 29 patients with chronic lymphocytic leukemia (CLL) refractory to therapy, including purine analogs in all cases, were treated with the monoclonal antibody, Campath-1H. (A 30-mg dose of Campath-1H was administered intravenously

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

CMA-676 (gemtuzumab zogamicin) is an
antibody-targeted chemotherapeutic agent consisting of a humanized
anti-CD33 antibody linked to calicheamicin, a potent cytotoxic

Originally described in the 1980s, mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent, B-cell lymphoma that has been reclassified by the revised European-American Lymphoma (REAL) classification system as extranodal, marginal

We evaluated the safety and efficacy of
rituximab (Rituxan) in combination with CHOP (cyclophosphamide,
doxorubicin HCl, Oncovin, and prednisone) in a study of 40 patients
(31 treatment-naive, 9 previously treated) with low-grade/follicular

Treatment of recurrent or nucleoside analog–refractory hairy cell leukemia (HCL) may be limited by poor tolerance (eg, interferon), profound CD4 lymphopenia, or comorbid conditions in which prolonged myelosuppression from nucleoside analog

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).

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.

One important future direction for rituximab (Rituxan) is to expand its therapeutic role into other CD-positive disorders. Rituximab induces responses in up to one-third of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

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.

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.

The National Institutes of Health (NIH) is sponsoring a Consensus Development Conference on Adjuvant Therapy for Breast Cancer, to be held in Bethesda, Maryland, on November 1-3, 2000.

A total of 77 patients have been entered into
an ongoing, randomized protocol integrating rituximab (Rituxan) with
chemotherapy for patients with newly diagnosed stage IV indolent
lymphoma. Patients are receiving FND (fludarabine

Low toxicity and high efficacy have been observed after treatment of patients with relapsed low-grade follicular non-Hodgkin’s lymphoma (NHL) using the chimeric monoclonal anti-CD20 antibody rituximab (Rituxan). Since the CD20-

The efficacy and toxicity of readministration of rituximab (Rituxan) in patients with indolent B-cell non-Hodgkin’s lymphoma (NHL) that recurs after an initial response to rituximab are unknown.

American men and women are living longer than ever before. The gender disparity in life expectancy is narrowing, as the increase in longevity among men continues to outpace that among women. The projected life expectancy of a boy born in

Iodine-131 tositumomab (Bexxar), a radiolabeled immunoglobulin G2a (IgG2a) monoclonal antibody directed against the CD20 antigen, is effective in the treatment of previously untreated, as well as relapsed and refractory, low-grade and transformed, low-grade non-Hodgkin’s lymphoma (NHL).

Ibritumomab tiuxetan (Zevalin) is an anti-CD20
murine immunoglobulin G1 (IgG₁) kappa monoclonal antibody
conjugated to tiuxetan that forms a strong chelate with the pure
beta-emitting isotope yttrium-90 (⁹⁰Y). Mechanisms of
action include

As a practicing physician, Dr.Ost’s perspective on the use of photodynamic therapy (PDT) in the treatment of lung cancer is informative and helpful, particularly regarding its application in the multimodality setting. My comments represent the viewpoint of a scientist involved in the clinical use of PDT in an academic tertiary referral institution.

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

While response rates of 50% have been reported after treatment of patients with low-grade follicular non-Hodgkin’s lymphoma (NHL) using the chimeric monoclonal anti-CD20 antibody rituximab (Rituxan), only minimal data are available on

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.

Rituximab (Rituxan) therapy is successfully used to treat many B-cell malignancies. Absent or diminished CD20 expression on certain B-cell tumors may limit the efficacy of CD20-directed serotherapies

Multiple myeloma is a neoplastic disease characterized by the expansion of monoclonal plasma cells that seed throughout the bone marrow. Induction regimens for multiple myeloma result in a 60% to 70% response rate. In vitro studies suggest

There is no standard treatment of stage III-IV follicular lymphoma patients with a low-tumor burden. Rituximab (Rituxan), a chimeric anti-CD20 antibody, is active in pretreated patients with an overall response (OR) rate of 50% and good tolerance.