Tumour response and radiation-induced lung injury in patients with recurrent small cell lung cancer treated with radiotherapy and concomitant interferon-alpha.
The aim of this study was to determine whether either natural or recombinant interferon (IFN)-alpha can improve the response to radiotherapy (RT) in patients with small cell lung cancer (SCLC), and to assess the role of IFN in radiation-induced lung injury. All patients had previously participated in a randomised trial of chemotherapy alone or in combination with IFN-alpha in three arms (arm O: no IFN, arm I: natural IFN-alpha, arm II: recombinant IFN-alpha). Patients with locally progressive disease in the lungs following chemotherapy were treated with RT and they continued with their concomitant IFN-alpha. The RT dose was 50 Gy. Radiation-induced lung injury was assessed by lung function tests, computed tomography and bronchoalveolar lavage fluid (BALF) analysis which included cell findings, Interleukin (IL)-1 alpha/-1 beta expression by alveolar macrophages and surfactant components. Seventeen patients were entered in the study, 16 of whom were evaluable. Response rates in Arms O, I and II were 50, 67 and 50%, respectively. Median survival was 18.5, 7 and 23 months respectively, and 1-year survival was 67, 29 and 75% respectively. Long-term survival as assessed by 2- and 3-year survival rates was 29% in patients receiving natural IFN-alpha as compared to 17% in patients not receiving IFN (not statistically significant findings). Every patient had abnormal results when assessed for radiation-induced lung injury. No statistically significant difference was found in toxicity between the treatment arms. A high surfactant protein (SP)-A/phospholipid ratio and a high level of SP-A in BALF before RT was associated with a high degree of radiation-induced lung injury measured by lung function tests and computed tomography in all arms of the study. Thus, we could not show that the combination of IFN-alpha and RT induced more lung toxicity than RT alone as we did in our previous study. The role of high SP-A/phospholipid ratios and high SP-A levels in BALF before RT as predictors of the development of lung injury after RT needs to be determined in the future.
Halme
M
M
Department of Medicine, Helsinki University Central Hospital, Finland.
Hallman
M
M
Ruotsalainen
T
T
Piilonen
A
A
Taskinen
E
E
Pekonen
M
M
Maasilta
P
P
Mattson
K
K
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D002452:Cell Count; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011510:Proteolipids / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism; D017564:Radiation Pneumonitis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D006023:Glycoproteins; D007370:Interferon Type I; D007375:Interleukin-1; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins