Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, Phase I-II study.
OBJECTIVE
This study evaluated the toxicity and tumor efficacy of the halopyrimidine IUdR as a chemical modifier of radiation response in patients with malignant glioma. The preliminary results published in 1993 demonstrated no real advantage in the group of patients with glioblastoma. However, a benefit appeared to be evolving in the group of patients with Anaplastic Astrocytoma (AA). We are now presenting the results on the long-term follow-up of patients with AA.


METHODS
Between August 1987 and October 1991, 79 patients were entered in a prospective study with newly diagnosed malignant glioma. Twenty-one of 79 were AA. The study was designed to have a fixed dose of radiation consisting of 60.16 Gy in 32 fractions in 6.5 weeks but varying the dose schedule of IUdR, delivered in a continuous intravenous infusion of long (96 h) or short (48 and 24 h) duration, every week for the 6.5 weeks of radiation treatment.


RESULTS
The last AA patient was entered in March 1991. Ninety-five percent of the AA patients were under 59 years of age and 86% had a Karnofsky score 80. Thirty-eight percent had a tumor diameter of less than 5 cm and 52% had a tumor diameter between 5-10 cm. Seventy-six percent had partial or total tumor resection. The toxicity of this treatment was acceptable and has already been published elsewhere. At the time of this report, 14 out of 21 patients with AA are dead. The median survival, calculated from the Kaplan-Meier, is 3.2 years. Thirty-three percent of the patients have survived 5 years. These results compare favorably with the best results reported in the literature with postoperative external radiation plus chemotherapy, median survival time (MST) of 3 years, and previous Radiation Therapy Oncology Group (RTOG) experience with radiation alone, MST of 2 years.


CONCLUSIONS
Our findings in patients with AA corroborate the improved therapeutic results published recently when combining external radiation with "long" infusion of i.v. BUdR and indicate the need to proceed with randomized Phase III studies utilizing halogenated pyrimidines and radiation. One such study has already been activated, RTOG # 94-04.
Urtasun
R C
RC
Cross Cancer Institute and University of Alberta, Edmonton, Canada.
Kinsella
T J
TJ
Farnan
N
N
DelRowe
J D
JD
Lester
S G
SG
Fulton
D S
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005909:Glioblastoma / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use*; D008875:Middle Aged; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D011838:Radiation-Sensitizing Agents; D007065:Idoxuridine