News

WASHINGTON-Walden-ström’s macroglobulinemia is a rare low-grade B-cell lymphoproliferative disorder. Patients with Waldenström’s also often have small lymphocytic lymphoma (SLL). Hyperviscosity in Waldenström’s responds temporarily to plasmapheresis. Alkylator therapy, fludarabine (Fludara), and cladribine (Leustatin) are effective in many cases, but there are no good options for patients refractory to purine analogs.

Rituximab (IDEC-C2B8 [Rituxan]) is a chimeric anti-CD20 monoclonal antibody (MoAb) that was recently approved by the FDA for the treatment of patients with low-grade or follicular B-cell non-Hodgkin’s lymphoma. Its potential efficacy in other B-cell malignancies is currently being explored. This article reviews the mechanisms of action of rituximab, as well as preclinical data and results of the clinical trials that led to its approval. Also discussed are the mechanics of administering rituximab on the recommended weekly ´ 4 outpatient schedule. Finally, the article describes ongoing and planned trials of rituximab in other dosage schedules, in other B-cell neoplasms, and in conjunction with chemotherapy. As the first MoAb to gain FDA approval for the treatment of a malignancy, rituximab signals the beginning of a promising new era in cancer therapy. [ONCOLOGY 12(12):1763-1770, 1998]

SAN DIEGO--The longest follow-up studies to date on dose-intensive therapy with peripheral blood stem cell or bone marrow support in patients with Hodgkin’s disease or non-Hodgkin’s lymphoma (NHL) show some promising results with specific drug regimens.

INDIANAPOLIS--Eli Lilly and Company’s Gemzar (gemcitabine) has received FDA approval for use as first-line treatment of inoperable, locally advanced, or metastatic non-small-cell lung cancer (NSCLC) in combination with cisplatin (Platinol). The agent was previously approved as first-line, single-agent therapy of locally advanced or metastatic pancreatic cancer

It was not until 1995 that a phase III randomized trial demonstrated that autologous stem cell transplants (ASCT) improve the progression-free and overall survival of patients with relapsed refractory diffuse aggressive non-Hodgkin’s lymphoma. Investigators are now focusing on improving the clinical benefit of transplants. The relative contributions made by more intensive preparative regimens, purging, concomitant immunotherapy, and the timing of transplants are under study. Also, as transplant trials shift from relapsed disease to initial therapy, anticipated benefits must be balanced against both short-term and long-term toxicities.[ONCOLOGY 12(Suppl 8):56-62, 1998]

Doctors at the University of Pittsburgh Cancer Institute are exploring a new experimental therapy in which they transfer the tumor-suppressing gene TP53 (alias p53) into patients to reverse tumor progression. University of Pittsburgh clinical

BETHESDA, Md--A Food and Drug Administration panel has urged expanding the use of Photofrin (porfimer sodium, QLT PhotoTherapeutics) in lung cancer. In a unanimous vote, the Oncologic Drugs Advisory Committee (ODAC) recommended that the FDA approve the photodynamic therapy (PDT) for reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial non-small-cell lung cancer (NSCLC).

GENEVA--Highly active antiretroviral therapy (HAART), usually including a protease inhibitor, can suppress human immunodeficiency virus (HIV) so much that the immune system actually begins to heal, according to work presented at the 12th World Conference on AIDS. In patients who respond well to HAART, CD4+ and CD8+ cell counts move toward normal, and the risk of opportunistic infections decreases (see Oncology News International, August, 1998, pp 1 and 20).

WASHINGTON--Despite questions about dose levels and number of treatment courses, the FDA’s Oncology Drugs Advisory Committee (ODAC) gave a vote of confidence to Seragen’s Ontak (denileukin diftitox or DAB389IL-2) for its approval for use in cutaneous T-cell lymphoma (CTCL) that persists or recurs despite prior therapy. Ontak is an interleukin-2 (IL-2) fusion protein that delivers a diphtheria toxin fragment to lesions via IL-2 receptor binding. The panel was not asked to formally recommend the agent to the FDA.

It has been hypothesized that intratumoral thymidylate synthase (TS) gene expression might be used to select therapy for patients with disseminated colorectal cancer. We recently

LOS ANGELES--Preliminary results with a gene-therapy approach to recurrent prostate cancer suggest antitumor activity in at least some patients. Three of 18 patients have had decreases in PSA levels of more than 50%. The effects have persisted for 45 to 290 days, including one patient who became biopsy negative for a brief period of time.

CHICAGO--A role is emerging for multimodality therapy in the treatment of both resectable and unresectable stage III non-small-cell lung cancer (NSCLC). When given as an adjunct to radiotherapy or surgery, chemotherapy can downstage local disease and control systemic disease spread by eliminating micro-metastases or delaying the development of metastases, Ann Mauer, MD, a senior fellow in oncology at the University of Chicago, said at the International Conference of the American Thoracic Society and American Lung Association.

In order for the immune system to protect against cancer, it must recognize tumors as "non-self." Markers present on the surface of tumors, known as antigens, allow the immune system to recognize tumors as non-self. However, in order for the

Scientists at Ohio University Edison Biotechnology Institute have used a nonviral gene expression system, invented and patented by Ohio University several years ago, to eliminate human cancer cells in animals. The investigators reported achieving

HOUSTON--Adenoviral-p53 gene therapy with Introgen Therapeutics’ INGN 201 was well tolerated and showed evidence of clinical activity both alone and with cisplatin (Platinol) in patients with advanced non-small-cell lung cancer (NSCLC) who had failed conventional therapy. Stephen Swisher, MD, of the M. D. Anderson Cancer Center, presented the completed phase I/II trial results at an ASCO poster session.

CHICAGO--Molecular biologic markers may be able to identify patients with early-stage non-small-cell lung cancer (NSCLC) who are at the highest risk for metastasis and therefore may benefit from aggressive therapy.

NEW ORLEANS--After delivery with a cationic liposome complex, the tumor-suppressor gene E1A was expressed by cells in many places in the body, Naoto Ueno, MD, of the M.D. Anderson Cancer Center, reported at the 89th annual meeting of the American Association for Cancer Research (AACR).

BETHESDA, Md--Bristol-Myers Squibb went 2-for-2 before the FDA’s Oncologic Drugs Advisory Committee (ODAC). The panel recommended that the FDA approve injectable Taxol (pacli-taxel), in combination with cisplatin (Platinol), for both the first-line treatment of ovarian cancer and for the treatment of non-small-cell lung cancer (NSCLC) in patients who are not candidates for potentially curative surgery and/or radiation therapy.

Prophylactic cranial irradiation (PCI) is being reintroduced into multimodality treatment protocols of patients with small-cell lung cancer (SCLC). The history of its use brings interesting insights into clinical evaluations of treatment strategies and design of relevant and informative trials. The critical issues of effectiveness and overall health gains of prophylactic cranial irradiation have been addressed in a series of recently completed clinical trials. These trials tested prophylactic cranial irradiation in small-cell lung cancer patients achieving good response to induction therapy and confirmed the ability of standard prophylactic cranial irradiation schedules to significantly reduce the lifetime risk of brain metastases. A subset of these trials evaluated neurotoxicity in a formal and prospective manner. No sustained or significant detriment in neuropsychometric function could be linked to the use of prophylactic cranial irradiation. In addition, all the large trials have shown a consistent survival advantage in favor of the prophylactic cranial irradiation arm. None of the individual sample sizes were large enough to statistically confirm this survival benefit, but a meta-analysis is in progress and will report on this aspect of evidence shortly. Issues that remain to be answered are the optimal dose and schedule of prophylactic cranial irradiation as well as the timing of this administration. These questions form the nucleus of the next generation of collaborative trials that are being designed.[ONCOLOGY 12(Suppl 2):19-24, 1998]

Preclinically, the taxanes appear to potentiate radiation more effectively than do the platinum compounds. In our phase I trial (LUN-17) in patients with advanced non-small-cell lung cancer, we defined the maximum tolerated

Non-small-cell lung cancer (NSCLC) will increasingly come under better control as the current approaches to therapy are more broadly employed and as new therapies are deployed against recently elucidated molecular

Lung cancer is the leading cause of death due to cancer in the United States, and approximately 178,100 new cases were estimated to occur last year. Small-cell lung cancer (SCLC) accounts for approximately 17% to 25% of all lung cancers. Due to its aggressive nature and rapid proliferation rate, small-cell lung cancer is usually widespread at diagnosis. Therefore, chemotherapy is the cornerstone of therapy for this disease. Cisplatin (Platinol) is an active chemotherapeutic agent used to treat small-cell lung cancer, but its toxicity, including nausea and vomiting, nephrotoxicity, neurotoxicity, and ototoxicity, has led to the investigation of combination regimens with different toxicity profiles. Carboplatin (Paraplatin), a derivative of cisplatin, has far less nonhematologic toxicity, although myelosuppression may be slightly greater than that observed with cisplatin. The reduced toxicity and equivalent efficacy of carboplatin have resulted in the increased use of carboplatin-based regimens to treat small-cell lung cancer. Phase I and II trials of carboplatin as single-agent treatment for small-cell lung cancer resulted in overall response rates of approximately 60% for previously untreated patients and 17% for those who had received prior therapy. New combination chemotherapy regimens that include carboplatin may improve survival in patients with small-cell lung cancer and potentially cure those patients with limited disease. Further investigation of carboplatin and other new agents is warranted.[ONCOLOGY 12(Suppl 2):36-43, 1998]

We report here the preliminary results of a large phase II multicenter study done in the community setting, using paclitaxel (Taxol) (given by 1-hour infusion) plus carboplatin (Paraplatin) to treat patients with advanced non-small-cell lung cancer (NSCLC). In this study, 155 chemotherapy-naive patients with stage IIIB, stage IV, or recurrent metastatic non-small-cell lung cancer received the two drugs in 21-day cycles. Paclitaxel 225 mg/m² was given by 1-hour intravenous infusion followed immediately by carboplatin at a targeted area under the concentration-time curve of 6.0 (calculated according to the Calvert formula). Colony-stimulating factors were not used routinely. Objective responses occurred in 53 of 155 patients (34%) (53 of 144 [36%] evaluable patients) including three complete responses and 50 partial responses. Fifty-two other patients had stable disease at initial reevaluation. The median survival among all 155 patients was 8 months; the 1-year survival rate was 42%, and the 2-year survival rate was 20%. Leukopenia and cumulative peripheral neuropathy occurred consistently but rarely were severe or affected the course of therapy. One patient died due to sepsis. Other grade 3 and grade 4 toxicities were uncommon. This paclitaxel-carboplatin combination chemotherapy appears to be a relatively convenient, safe, and active regimen in advanced non-small-cell lung cancer.[ONCOLOGY 12(Suppl 2):71-73, 1998]

Although the need to combine thoracic radiotherapy with systemic chemotherapy in the curative treatment of limited small-cell lung cancer is now widely acknowledged, there is substantial disagreement on how best to do this. This paper reviews radiotherapeutic factors but also highlights the important interactions that occur with some classes of chemotherapeutics. Studies examining variables like dose and volume are clearly in order. Concurrent therapy given early has been adopted throughout most of the world, except Europe. The reasons for this are explored. Multiple studies are now showing excellent results with fewer total cycles of chemotherapy. Integrationof newer drugs is another challenge for clinical investigators at the close of this century. [ONCOLOGY 12(Suppl 2):15-18, 1998]

For more than 25 years, chemotherapy has been the cornerstone of treatment for small-cell lung cancer. Many studies have tested a wide variety of drugs in different combinations, resulting in a number of standard

Rituximab (Rituxan) has been cleared for marketing by the FDA. Previously known as the C2B8 antibody, rituximab, is a single-agent monoclonal antibody therapy for relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-

Newer chemotherapy drugs have shown encouraging activity in advanced non-small-cell lung cancer. Based on these improved outcomes, as well as the high rate of distant relapse in patients with locally advanced disease, several recent studies have evaluated the use of systemic therapy in patients with earlier-stage disease.

DUBLIN-Preliminary results suggest that the use of single-agent topotecan (Hycamtin) as second-line therapy for small-cell lung cancer (SCLC) in patients who failed after an initial response to first-line therapy provides efficacy similar to that of the commonly used regimen of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV).

SAN FRANCISCO-About 4,000 human diseases have a genetic cause, and many such diseases are untreatable or poorly treated by conventional medicine, said R. Michael Blaese, MD, chief of the Clinical Gene Therapy Branch at the NIH National Center for Human Genome Research. In theory, many of these diseases could be treated by adding, deleting, or altering genes.

BETHESDA, Md-The Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) has recommended approval of QLT Photo-Therapeutics’ Photofrin (porfimer sodium) for use as photodynamic therapy (PDT) of T1 stage endobronchial carcinoma in patients with non-small-cell lung cancer (NSCLC) for whom surgery and radiotherapy are not indicated.