CLINICAL CANCER LETTER Cancer Research News for Clinicians
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Vol. 27 No. 1 THE January 2004 CLINICAL CANCER LETTER Cancer research news for clinicians © Copyright 2004 American Society of Hematology: The Cancer Letter Inc. New Treatment Approaches For A Variety All rights reserved. Of Leukemias Described At ASH Meeting By Lawrence M. Prescott SAN DIEGO—A number of new treatment approaches appear to ASH Annual Meeting: be of real value in patients with a variety of leukemias including acute Trisenox In Children promyelocytic leukemia, chronic lymphocytic leukemia, acute myeloid With APML leukemia, and chronic myeloid leukemia, according to investigators . Page 2 presenting their findings at the 45th annual meeting of the American Society of Hematology last month. (Continued to page 2) Campath In CLL . Page 2 ASH Highlights: Improved Treatments For NHL, Genasense In AML Poor Prognostic Factors For B-Cell In Children . Page 3 By Lawrence M. Prescott SAN DIEGO—New therapeutic modalities for the treatment of Gleevec For CML adults with relapsed and aggressive non-Hodgkin’s lymphoma, as well as . Page 4 the identification of poor prognostic factors in children with advanced B- cell NHL and ways to combat this problem are proving to be of particular Zevalin In Mantle Cell benefit in developing effective therapeutic modalities for patients with . Page 4 forms of difficult-to-treat NHL, said investigators at the 45th annual meeting of the American Society of Hematology. Rituxan In NHL . Page 6 Pixantrone in Relapsed Aggressive NHL A variant of the CHOP (cyclophosphamide, vincristine, prednisone, Sphingosomal Vincristine and doxorubicin) regimen, which substitutes the new anthracycline-derived drug pixantrone for doxorubicin in elderly patients with aggressive NHL Tested in Relapsed NHL who had failed prior doxorubicin-containing CHOP, proved to be a feasible . Page 6 and safe approach for the treatment of multiple relapsed aggressive NHL in these difficult-to-treat patients, said Peter Borchmann, hematologist/ Poor Prognostic Factors oncologist, Klinik fur Innere Medizin, University of Cologne, Germany. In Children With B-NHL “This new agent, as a replacement for doxorubicin, in combination . Page 7 with the CHOP-like regimen is highly active and well tolerated and appears to be very promising in this setting,” Borchmann said. Arixtra Prevents VTE The CHOP chemotherapy regimen is the standard-of-care treatment . Page 8 for newly diagnosed aggressive NHL, said Borchmann.While 70 percent of the patients respond to the CHOP therapy, and the regimen is curative in up to 35 percent to 40 percent of patients, the prognosis is poor for PO Box 9905 individuals who have a recurrence of the disease. Furthermore, despite Washington DC 20016 (Continued to page 5) Telephone 202-362-1809 Study Tests Trisenox with a median age of 12 years, were enrolled in this study from 1998 to 2003. All patients had the In Children With APML hypergranular variety of APML with an average (Continued from page 1) white blood cell count at presentation of 3380/mm3. Highlights of research presentations follow. Induction therapy consisted of intravenous arsenic trioxide 0.15 mg/kg daily until hematologic Arsenic Trioxide for APML remission, or a maximum of 60 days. This was In a study of the role of arsenic trioxide followed by a single course of consolidation therapy (Trisenox, Cti) in the primary treatment of pediatric lasting 28 days, one month after induction therapy. patients with acute promyelocytic leukemia, positive Monthly cycles of maintenance therapy, each lasting data was provided regarding the value of arsenic for 10 days, were administered for six months. trioxide in a pediatric setting, said Mammen Chandy, Nine of the 10 patients achieved hematologic a hematologist/oncologist at Christian Medical remission, Chandy said. One patient died on day 5 of College, Vallore, TN, India. therapy due to an intracranial hemorrhage. Median “Arsenic trioxide can achieve hematologic and time to hematologic remission was 49 days, ranging molecular remission in newly diagnosed children with from 41 to 60 days. Seven patients completed therapy; APML with no significant short-term toxicity,” said two are still on treatment. All patients continue in Chandy. “Long-term followup in a larger number of hematologic remission with a median followup of 24 patients is needed to evaluate late effects and to study months, ranging from 3 to 57 months. the minimum dose and duration of therapy with All 9 patients in hematologic remission are also arsenic trioxide required to reach a sustained in molecular remission, using a nested RT-polymerase remission in children with APML.” chain reaction with a sensitivity of 10-4 in peripheral Arsenic trioxide is a pharmaceutical grade blood, with a median followup of 22 months, ranging arsenic compound that is used in the U.S., Europe, from 1 to 57 months. and a number of countries in Asia to treat patients There was no significant short-term toxicity, with relapsed or refractory APML, Chandy said. Chandy said. Also, there is no cardiac or hepatic There is, however, very limited data on the role of toxicity. Minor hyperpigmentation of the skin and arsenic trioxide in the primary treatment of pediatric icthyosis occurred in five patients, but resolved after patients with APML. To assess the value of arsenic treatment was completed. Increased sleep and mild trioxide in this setting, 10 children aged 6 to 14 years, reversible peripheral neuropathy were seen in one patient each. Hyperleukocytosis was reported in 5 Member, patients, but this resolved with treatment. THE CLINICAL Newsletter and Electronic Publishers Association CANCER LETTER World Wide Web: http:// Alemtuzumab in CLL www.cancerletter.com The administration of alemtuzumab (Campath, Publisher: Kirsten Boyd Goldberg Berlex) for the elimination of minimal residual disease Editorial Assistant: Shelley Whitmore Wolfe after chemotherapy in patients with CLL results in a clearing of residual bone marrow disease in most Editorial: 202-362-1809 Fax: 202-318-4030 patients and a molecular remission in better than a PO Box 9905, Washington DC 20016 third of patients in whom polymerase chain reaction E-mail: [email protected] results were available, reported Susan O’Brien, professor of medicine, University of Texas M.D. Customer Service: 800-513-7042 Anderson Cancer Center. PO Box 40724, Nashville TN 37204-0724 “These and other data being presented at the American Society of Hematology meeting are THE CLINICAL CANCER LETTER (ISSN 164-985X). encouraging because they demonstrate that Campath Published monthly, subscription $99 per year, by The Cancer Letter Inc. All rights reserved. None of the content of this publication is a safe and effective treatment that induces a durable may be reproduced, stored in a retrieval system, or transmitted in response in CLL patients who show evidence of any form (electronic, mechanical, photocopying, facsimile, or residual disease following chemotherapy, improving otherwise) without prior written permission of the publisher. remissions induced by chemotherapy,” O’Brien said. Violators risk criminal penalties and $100,000 damages. “Furthermore, given the extent of treatment in these The Clinical Cancer Letter Page 2 January 2004 patients, the median time to progression of 42 months combined with a daunorubicin and cytarabine was very encouraging.” chemotherapy regimen proved to be a safe, potentially Alemtuzumab targets the CD52 antigen found active approach for the treatment of patients over on the surface of both cancerous and noncancerous the age of 60 with acute myeloid leukemia, according lymphocytes, but not on the surface of cells that have to Guido Marcucci, assistant professor of medicine, the ability to mature and differentiate into new, healthy Ohio State University. lymphocytes, O’Brien said. It is the first and only “Our data suggest that Genasense in humanized monoclonal antibody approved for B-CLL combination with standard 7+3 cytarabine- and has been shown to be of proven efficacy in daunorubicin induction is feasible with no additional patients who have failed both alkylating agents and toxicity, including cardiotoxicity, observed beyond that fludarabine phosphate treatment. commonly seen with daunorubicin and cytarabine The purpose of this trial was to evaluate the therapy,” Marcucci said. “The 10-day infusion of efficacy of alemtuzumab in patients who had partial Genasense at 7 mg/kg daily is well tolerated.” remission (PR) after chemotherapy but had residual Oblimersen sodium works by inhibiting the disease in their bone marrow and/or lymph nodes, production of Bcl-2, a protein made by cancer cells O’Brien said. Fifty-eight patients with a PR, nodular that is thought to block chemotherapy-induced cell PR (nPR), or complete remission (CR) with evidence death, Marcucci said. Expression of Bcl-2 may render of disease on immunophenotyping were eligible. AML cells resistant to chemotherapy and has been Alemtuzumab was administered at a dose of 10 mg associated with unfavorable outcome. Obimersen intravenously three times a week (TIW) for four sodium is a phosphorothiate 18-mer antisense weeks. This was followed by a four-week rest period. oligonucleotide directed against the first six codons If disease was still present, patients were given of Bcl-2. By reducing the amount of Bcl-2 in cancer another four weeks of alemtuzumab at 30 mg TIW. cells, oblimersen sodium may enhance the All patients received prophylactic trimethoprin-sulfa effectiveness of current anticancer treatments. and valacyclovir. Treatment