Successful multifold dose escalation of anti-GD2 monoclonal antibody 3F8 in patients with neuroblastoma: A phase I study Journal Article

Authors: Kushner, B. H.; Kramer, K.; Modak, S.; Cheung, N. K. V.
Article Title: Successful multifold dose escalation of anti-GD2 monoclonal antibody 3F8 in patients with neuroblastoma: A phase I study
Abstract: Purpose: Pain can hinder immunotherapy with anti-GD2 monoclonal antibodies (MoAbs) like 3F8. Heat-modified 3F8 (HM3F8) lacks effector functions and could mask GD2 or cross-reactive epitopes on nerves, thereby preventing a subsequent dose of unmodified 3F8 from activating pain fibers. We hypothesized that 3F8 dose escalation is possible without increased analgesic requirements in patients pretreated with HM3F8. Patients and Methods: Thirty patients with resistant neuroblastoma (NB) received one to two cycles of 3F8 plus granulocyte-macrophage colony-stimulating factor. 3F8 dosing began at 20 mg/m2/d and increased by 20 mg/m2/d in the absence of dose-limiting toxicity (DLT). Premedication included analgesics, antihistamines, and 5-minute infusions of HM3F8. On the basis of experience with 3F8 10 mg/m2/d in prior protocols, the DLT of pain was defined as more than seven doses of opioids administered within 2 hours. Opioid use was compared with a contemporary control group treated with 3F8 20 mg/m2/d but no HM3F8. Disease response was assessed. Results: Treatment was administered in the outpatient setting. Dose escalation stopped at 160 mg/m2/d because of drug supply limitations; even through this dosage level, analgesic requirements were similar to historical controls, and there were no DLTs. Analgesic requirements at 3F8 dosage levels through 80 mg/m2/d were significantly less compared with controls. Anti-NB activity occurred at all dosages. Conclusion: Multifold dose escalation of 3F8 is feasible. The findings can be interpreted as compatible with the possibility that HM3F8 can modify toxicity without blunting anti-NB activity. This pain control strategy may help achieve dose escalation with other anti-GD2 MoAbs. © 2011 by American Society of Clinical Oncology.
Keywords: adolescent; adult; child; clinical article; controlled study; preschool child; school child; treatment response; unclassified drug; drug efficacy; drug safety; hypertension; side effect; unspecified side effect; multiple cycle treatment; pain; monoclonal antibody; abdominal pain; drug dose escalation; drug fever; hypoalbuminemia; hypokalemia; hyponatremia; thorax pain; neuroblastoma; erythema; phase 1 clinical trial; drug dose increase; analgesia; recombinant granulocyte macrophage colony stimulating factor; urticaria; monoclonal antibody 3f8; heat modified 3f8
Journal Title: Journal of Clinical Oncology
Volume: 29
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2011-03-20
Start Page: 1168
End Page: 1174
Language: English
DOI: 10.1200/jco.2010.28.3317
PROVIDER: scopus
PMCID: PMC3083872
PUBMED: 21343563
Notes: --- - "Export Date: 23 June 2011" - "CODEN: JCOND" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Brian Kushner
    270 Kushner
  2. Nai-Kong Cheung
    579 Cheung
  3. Kim Kramer
    204 Kramer
  4. Shakeel Modak
    208 Modak