Affiliation:
1. From the Henry Ford Health System, Detroit, MI; Radiation Therapy Oncology Group; Fox Chase Cancer Center; Thomas Jefferson University; Hospital of the University of Pennsylvania, Philadelphia, PA; M.D. Anderson Cancer Center, Houston, TX; Medical College of Wisconsin, Milwaukee, WI; University of California Los Angeles School of Nursing, Los Angeles, CA; Washington University, St Louis, MO; and Tom Baker Cancer Center, Calgary, Alberta, Canada
Abstract
Purpose To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms. Patients and Methods A total of 243 patients with stage II to IIIA/B non–small-cell lung cancer received induction paclitaxel 225 mg/m2 intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m2 IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs. Results A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of ≥ grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87). Conclusion AM did not significantly reduce esophagitis ≥ grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.
Publisher
American Society of Clinical Oncology (ASCO)
Reference34 articles.
1. Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Mitomycin, Vindesine, and Cisplatin in Unresectable Stage III Non–Small-Cell Lung Cancer
2. Curran WJ Jr, Scott C, Langer C, et al: Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 22:621,2003,
3. Komaki R, Seiferheld W, Curran W, et al: Sequential vs. concurrent chemotherapy and radiation therapy for inoperable non-small cell lung cancer (NSCLC): Analysis of failures in a phase III study (RTOG 9410). Int J Radiat Oncol Biol Phys 48:113,2003,
4. The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies
5. Calabro-Jones PM, Fahey RC, Smoluk GD, et al: Alkaline phosphatase promotes radioprotection and accumulation of WR-1065 in V79-171 cells incubated in medium containing WR-27821. Int J Radiat Oncol Biol Phys 47:23,1985-27,
Cited by
195 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献