Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer.

Abstract

PURPOSE:

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.

PATIENTS AND 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.

CONCLUSION:

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.

• Authors: Swan Swan Leong, Eng Huat Tan, Kam Weng Fong, Einar Wilder-Smith, Yew Kwang Ong, Bee Choo Tai, Lita Chew, Shih Hui Lim, Joseph Wee, Khai Mun Lee, Kian Fong Foo, Peter Ang, Peng Tiam Ang
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 9 Pg. 1767-74 (May 01 2003) ISSN: 0732-183X [Print] United States
• PMID: 12721253 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Radiation-Protective Agents
• Carboplatin
• Amifostine
• Paclitaxel

Topics

• Adult
• Aged
• Amifostine (administration & dosage, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology, radiotherapy)
• Combined Modality Therapy
• Double-Blind Method
• Esophagitis (etiology, prevention & control)
• Female
• Humans
• Infusions, Intravenous
• Lung Neoplasms (drug therapy, pathology, radiotherapy)
• Male
• Middle Aged
• Paclitaxel (administration & dosage)
• Placebos
• Radiation Injuries (prevention & control)
• Radiation-Protective Agents (administration & dosage, pharmacology)
• Treatment Outcome