Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer.
OBJECTIVE
Greater toxicities have been recognized to be a consequence of combined chemotherapy and radiotherapy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This study was designed to determine if the use of amifostine could reduce treatment-related toxicities associated with the use of paclitaxel plus carboplatin and thoracic radiotherapy.


METHODS
Sixty patients with unresectable stage III NSCLC were treated with two cycles of paclitaxel 175 mg/m2 and carboplatin (area under the time-concentration curve = 6), followed by thoracic radiotherapy (64 Gy) with concurrent weekly paclitaxel 60 mg/m2. Patients were randomly assigned to receive 740 mg/m2 of amifostine (arm A) or placebo (arm B) before each dose of paclitaxel and carboplatin. Treatment-related toxicities were evaluated at each visit and nerve conduction tests were performed before and after treatment for the objective assessment of neurotoxicity.


RESULTS
There was no significant difference between arms A and B in grade 3 to 4 neutropenia. In all 72 neurophysiological parameters measured, there was no significant difference between the two treatment arms, although there was a trend toward fewer patients showing deterioration in arm A for six of the parameters. Grade 2 to 3 esophagitis occurred in 43% of patients in arm A and in 70% of patients in arm B. The difference of -27% (95% confidence limit = -50%, 0.4%) was not statistically significant. Response rates and survival were also not significantly different between the two arms.


CONCLUSIONS
Pretreatment with amifostine showed a trend toward reducing the severity of esophagitis associated with concurrent chemoradiotherapy, but it did not reach statistical significance. There was no significant protective effect on hematologic or neurologic toxicities induced by paclitaxel and carboplatin.
Leong
Swan Swan
SS
Department of Medical Oncology, National Cancer Centre, 11 Hospital Dr, Singapore 169610. dmolss@nccs.com.sg
Tan
Eng Huat
EH
Fong
Kam Weng
KW
Wilder-Smith
Einar
E
Ong
Yew Kwang
YK
Tai
Bee Choo
BC
Chew
Lita
L
Lim
Shih Hui
SH
Wee
Joseph
J
Lee
Khai Mun
KM
Foo
Kian Fong
KF
Ang
Peter
P
Ang
Peng Tiam
PT
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004941:Esophagitis / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010919:Placebos; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
D010919:Placebos; D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine; D017239:Paclitaxel