ONCOLOGY Vol 14 No 3

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

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

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

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.

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]

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.

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.

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.

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.