Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer.
OBJECTIVE
Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population.


METHODS
Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease.


RESULTS
Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively.


CONCLUSIONS
Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting.
North Central Cancer Treatment Group, Mayo Clinic, Rochester, MN 55905.
E G
EG
Shaw
R L
RL
Deming
E T
ET
Creagan
S
S
Nair
J Q
JQ
Su
R
R
Levitt
P D
PD
Steen
M
M
Wiesenfeld
J A
JA
Mailliard
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins; D012074:Remission Induction
D011994:Recombinant Proteins; D007371:Interferon-gamma