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 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: JCOND" - "Source: Scopus" |
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