Effect of amifostine on toxicities associated with sequential chemotherapy and radiation therapy for unresectable non-small-cell lung cancer: results of a phase II trial.
OBJECTIVE
To determine the effect of amifostine on the safety and efficacy of induction chemotherapy with high-dose cisplatin and vinblastine followed by large-field thoracic irradiation to 60 Gy in patients with stage IIIA or IIIB non-small-cell lung cancer (NSCLC).


METHODS
Twenty-six patients with unresectable stage IIIA or IIIB NSCLC were entered onto the study between May 1991 and November 1994. Patients received amifostine (740 or 910 mg/m2) followed by cisplatin (120 mg/m2) on days 1 and 29. Vinblastine (5 mg/m2) was given weekly for 5 weeks with no amifostine pretreatment. Following chemotherapy, patients received amifostine (340 mg/m2 4 days a week for 5 weeks, or 200 mg/m2 5 days a week for 6 weeks) 15 minutes before definitive thoracic radiation therapy to a total dose of 60 Gy in 6 weeks.


RESULTS
Twenty-five patients were assessable for response and survival. The objective response rate was 60%. One-, 2-, and 3-year survival rates were 55%, 23%, and 23%. There was no grade 3 or greater renal toxicity during chemotherapy or grade 3 or greater esophagitis during radiation therapy. Neutropenia (secondary to vinblastine use) was the only grade 4 toxicity. There were no treatment-related deaths.


CONCLUSIONS
Amifostine can be administered safely with high-dose cisplatin, vinblastine, and radiation therapy for NSCLC. The response rate and survival data provide no evidence that amifostine impairs response to treatment. Amifostine appears to reduce cisplatin-related nephrotoxicity and radiation-induced esophagitis.
Tannehill
S P
SP
Department of Human Oncology, University of Wisconsin Medical School, Madison 53792-0600, USA.
Mehta
M P
MP
Larson
M
M
Storer
B
B
Pellet
J
J
Kinsella
T J
TJ
Schiller
J H
JH
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004941:Esophagitis / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011292:Premedication; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011878:Radiotherapy / Q000009:adverse effects; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
D011837:Radiation-Protective Agents; D014747:Vinblastine; D004999:Amifostine; D002945:Cisplatin