Premium
Phase 1 study of concurrent RMP‐7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas
Author(s) -
Packer Roger J.,
Krailo Mark,
Mehta Minesh,
Warren Katherine,
Allen Jeffrey,
Jakacki Regina,
Villablanca Judith G.,
Chiba Akiko,
Reaman Gregory
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21301
Subject(s) - medicine , carboplatin , radiation therapy , chemotherapy , nausea , toxicity , neutropenia , surgery , anesthesia , cisplatin
BACKGROUND Ninety percent of children with diffuse intrinsic brainstem tumors will die within 18 months of diagnosis. Radiotherapy is of transient benefit, and one way to potentially improve its efficacy is to add radiosensitizers. Carboplatin is antineoplastic and radiosensitizing. However, delivery to the primary tumor site is problematic. RMP‐7 is a bradykinin analog that causes selective permeability of the blood‐brain‐tumor interface. The goal of the current Phase I study was to determine the toxicity and feasibility of delivering RMP‐7 and carboplatin for 5 successive days during radiotherapy. METHODS RMP‐7 was given before the end of carboplatin infusion. Local radiotherapy (5940 centigrays) was given within 4 hours of completion of drug delivery. Duration of treatment was escalated in a stepwise, weekly fashion, in cohorts of 3, until there was treatment‐limiting toxicity or until radiotherapy was completed. Thirteen patients were treated, whose median age was 7 years (range, 3–14 yrs). RESULTS One child died early in treatment of progressive disease and was not assessable for toxicity. Treatment for 3, 4, or 5 weeks was tolerated well, with mild flushing, tachycardia, nausea, emesis, dizziness, and abdominal pain. Of 3 children treated at the full duration of therapy (33 doses over 7 wks), 1 developed dose‐limiting hepatotoxicity and neutropenia. The estimated median survival period was 328 days, and 1 patient remained disease progression free > 400 days from initiation of treatment. CONCLUSIONS The results of the current study confirmed the feasibility of giving RMP‐7 and carboplatin daily during radiotherapy. Cancer 2005. © 2005 American Cancer Society.