Outcome after reduced chemotherapy for intermediate-risk neuroblastoma
David L Baker, Mary L Schmidt, Susan L Cohn, John M Maris, Wendy B London, Allen Buxton, Daniel Stram, Robert P Castleberry, Hiroyuki Shimada, Anthony Sandler, Robert C Shamberger, A Thomas Look, C Patrick Reynolds, Robert C Seeger, Katherine K Matthay, Children’s Oncology Group, Martha Greenwood, Sharad Salvi, Vikramjit Kanwar, Douglas Strother, Christopher Frantz, Doured Daghistani, Satkiran Grewal, Cynthia Kretschmar, Mason Bond, Rajen Mody, Rochelle Yanofsky, William Ferguson, Mandy Atkinson, Daniel McMahon, Bruno Michon, Lolie Yu, James Feusner, Vonda Crouse, Steven Kuerbitz, Jacqueline Halton, Yaddanapudi Ravindranath, Emmett Broxson, Jeffrey Dome, Leo Mascarenhas, Violet Shen, Frank Balis, Eric Lowe, Bruce Bostrom, David Walterhouse, John Perentesis, Tanya Tekautz, Alice Lee, Michael Isakoff, Meaghan Granger, Latha Prasannan, Carlos Rodriguez-Galindo, Sara Chaffee, Sharon Lockhart, M Cris Johnson, Susan Kreissman, Ray Pais, Howard Katzenstein, Clifford Selsky, Jeffrey Taylor, Aziza Shad, Cary Stroud, Burton Appel, Jerry Finklestein, David Dickens, Yvan Samson, Ronald Grant, Robert Fallon, Marshall Schorin, John Hand, Robert Arceci, Vincent Kiley, Jeffrey Lobel, Mariana Silva, Salvatore Bertolone, Emad Salman, Janice Olson, Antranik Bedros, Jong-Hyo Kwon, Eric Larsen, Michael McManus, Ronald Louie, Howard Weinstein, Carola Arndt, Carol Portwine, Carl Lenarsky, Colleen McDonough, Jacqueline Kraveka, J Johnston, Iftikhar Hanif, Rama Jasty, Nathan Kobrinsky, Jaime Estrada, Renuka Gera, Michael Kelly, Rosanna Ricafort, Eugenia Chang, Gregory Kirkpatrick, Amanda Termuhlen, Eric Sandler, Jonathan Bernstein, Mehmet Ozkaynak, Peri Kamalakar, John Neely, Jessica Boklan, Paulette Bryant, Phillip Barnette, Catherine Cole, William Roberts, Yousif Joe Matloub, Torrey Mitchell, Cindy Schwartz, Martin Brecher, David Ashley, Helen Irving, Judy Felgenhauer, Assanasen Chatchawin, Tebbi Cameron, Hill John, Razzouk Bassem, Clavell Luis, Greenfield Daniel, Mpofu Christopher, Redner Arlene, Hawkins Douglas, Wiley Joseph, Wayne Furman, Stephen Smith, Narayana Gowda, Neyssa Marina, Sunil Jayantilal Desai, Irene Cherrick, Yisheng Lee, Roland Ammann, Maja Beck Popovic, Lisa Bomgaars, Curtis Turner, Kelly Maloney, Geoffrey McCowage, Maxine Hetherington, Susan Cohn, Dagmar Stein, Charles Scher, Cecilia Fu, Richard Drachtman, Alyssa Reddy, Brenda Wittman, David Becton, Robert Goldsby, Jonathan Ducore, Amy Smith, Mary Schmidt, Raymond Tannous, Mukta Kumar, Teresa York, Christopher Keuker, Joseph Neglia, Gail Megason, Thomas Loew, Stuart Winter, Stuart Gold, Rene McNall-Knapp, Arthur Ritchey, Lisa Hackney, Paul Thomas, Alan Homans, Kenneth De Santes, Naomi Winick, John Kuttesch, Anne Cairney, Kamar Godder, Thomas McLean, Robert Hayashi, Allen Chauvenet, Charles Main, Mark Weinblatt, Gary Kupfer, David L Baker, Mary L Schmidt, Susan L Cohn, John M Maris, Wendy B London, Allen Buxton, Daniel Stram, Robert P Castleberry, Hiroyuki Shimada, Anthony Sandler, Robert C Shamberger, A Thomas Look, C Patrick Reynolds, Robert C Seeger, Katherine K Matthay, Children’s Oncology Group, Martha Greenwood, Sharad Salvi, Vikramjit Kanwar, Douglas Strother, Christopher Frantz, Doured Daghistani, Satkiran Grewal, Cynthia Kretschmar, Mason Bond, Rajen Mody, Rochelle Yanofsky, William Ferguson, Mandy Atkinson, Daniel McMahon, Bruno Michon, Lolie Yu, James Feusner, Vonda Crouse, Steven Kuerbitz, Jacqueline Halton, Yaddanapudi Ravindranath, Emmett Broxson, Jeffrey Dome, Leo Mascarenhas, Violet Shen, Frank Balis, Eric Lowe, Bruce Bostrom, David Walterhouse, John Perentesis, Tanya Tekautz, Alice Lee, Michael Isakoff, Meaghan Granger, Latha Prasannan, Carlos Rodriguez-Galindo, Sara Chaffee, Sharon Lockhart, M Cris Johnson, Susan Kreissman, Ray Pais, Howard Katzenstein, Clifford Selsky, Jeffrey Taylor, Aziza Shad, Cary Stroud, Burton Appel, Jerry Finklestein, David Dickens, Yvan Samson, Ronald Grant, Robert Fallon, Marshall Schorin, John Hand, Robert Arceci, Vincent Kiley, Jeffrey Lobel, Mariana Silva, Salvatore Bertolone, Emad Salman, Janice Olson, Antranik Bedros, Jong-Hyo Kwon, Eric Larsen, Michael McManus, Ronald Louie, Howard Weinstein, Carola Arndt, Carol Portwine, Carl Lenarsky, Colleen McDonough, Jacqueline Kraveka, J Johnston, Iftikhar Hanif, Rama Jasty, Nathan Kobrinsky, Jaime Estrada, Renuka Gera, Michael Kelly, Rosanna Ricafort, Eugenia Chang, Gregory Kirkpatrick, Amanda Termuhlen, Eric Sandler, Jonathan Bernstein, Mehmet Ozkaynak, Peri Kamalakar, John Neely, Jessica Boklan, Paulette Bryant, Phillip Barnette, Catherine Cole, William Roberts, Yousif Joe Matloub, Torrey Mitchell, Cindy Schwartz, Martin Brecher, David Ashley, Helen Irving, Judy Felgenhauer, Assanasen Chatchawin, Tebbi Cameron, Hill John, Razzouk Bassem, Clavell Luis, Greenfield Daniel, Mpofu Christopher, Redner Arlene, Hawkins Douglas, Wiley Joseph, Wayne Furman, Stephen Smith, Narayana Gowda, Neyssa Marina, Sunil Jayantilal Desai, Irene Cherrick, Yisheng Lee, Roland Ammann, Maja Beck Popovic, Lisa Bomgaars, Curtis Turner, Kelly Maloney, Geoffrey McCowage, Maxine Hetherington, Susan Cohn, Dagmar Stein, Charles Scher, Cecilia Fu, Richard Drachtman, Alyssa Reddy, Brenda Wittman, David Becton, Robert Goldsby, Jonathan Ducore, Amy Smith, Mary Schmidt, Raymond Tannous, Mukta Kumar, Teresa York, Christopher Keuker, Joseph Neglia, Gail Megason, Thomas Loew, Stuart Winter, Stuart Gold, Rene McNall-Knapp, Arthur Ritchey, Lisa Hackney, Paul Thomas, Alan Homans, Kenneth De Santes, Naomi Winick, John Kuttesch, Anne Cairney, Kamar Godder, Thomas McLean, Robert Hayashi, Allen Chauvenet, Charles Main, Mark Weinblatt, Gary Kupfer
Abstract
Background: The survival rate among patients with intermediate-risk neuroblastoma who receive dose-intensive chemotherapy is excellent, but the survival rate among patients who receive reduced doses of chemotherapy for shorter periods of time is not known.
Methods: We conducted a prospective, phase 3, nonrandomized trial to determine whether a 3-year estimated overall survival of more than 90% could be maintained with reductions in the duration of therapy and drug doses, using a tumor biology-based therapy assignment. Eligible patients had newly diagnosed, intermediate-risk neuroblastoma without MYCN amplification; these patients included infants (<365 days of age) who had stage 3 or 4 disease, children (≥365 days of age) who had stage 3 tumors with favorable histopathological features, and infants who had stage 4S disease with a diploid DNA index or unfavorable histopathological features. Patients who had disease with favorable histopathological features and hyperdiploidy were assigned to four cycles of chemotherapy, and those with an incomplete response or either unfavorable feature were assigned to eight cycles.
Results: Between 1997 and 2005, a total of 479 eligible patients were enrolled in this trial (270 patients with stage 3 disease, 178 with stage 4 disease, and 31 with stage 4S disease). A total of 323 patients had tumors with favorable biologic features, and 141 had tumors with unfavorable biologic features. Ploidy, but not histopathological features, was significantly predictive of the outcome. Severe adverse events without disease progression occurred in 10 patients (2.1%), including secondary leukemia (in 3 patients), death from infection (in 3 patients), and death at surgery (in 4 patients). The 3-year estimate (±SE) of overall survival for the entire group was 96±1%, with an overall survival rate of 98±1% among patients who had tumors with favorable biologic features and 93±2% among patients who had tumors with unfavorable biologic features.
Conclusions: A very high rate of survival among patients with intermediate-risk neuroblastoma was achieved with a biologically based treatment assignment involving a substantially reduced duration of chemotherapy and reduced doses of chemotherapeutic agents as compared with the regimens used in earlier trials. These data provide support for further reduction in chemotherapy with more refined risk stratification. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003093.)
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Source: PubMed