Radiation Oncology/NSCLC/Miscellaneous

Role of Amifostine RTOG 98-01 (1998-2002) 15800308, 2005 — "Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01." Movsas B et al. J Clin Oncol. 2005 Apr 1;23(10):2145-54. 120 pts. Stage II-III NSCLC. Induction chemo and hyperfractionated RT with concurrent chemotherapy, randomized to +/- Amifostine. Grade 3 esophagitis 30% (Amifostine) vs 34%, N.S. However, improved swallowing diary area under the curve suggests a possible benefit. EGFR Gefitinib (Iressa) Is an inhibitor of the tyrosine kinase domain of EGFR. EGFR is overexpressed in 40-80% of NSCLC. Harvard, 2004 - 15118073 — "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib." Lynch TJ et al. N Engl J Med. 2004 May 20;350(21):2129-39. Most patients with NSCLC have no response to gefitinib, however about 10% show a rapid and dramatic response. A subgroup of patients with NSCLC have specific mutations in the EGFR gene which correlate with response to gefinitib. The mutations lead to increased growth factor signaling Conclusion: screening for EGFR mutations may enable selection of patients who will respond to treatment with gefitinib. IDEAL (Iressa Dose Evaluation in Advanced Lung Cancer) trials Previously treated NSCLC who failed 1-2 prior chemotherapy regimens. IDEAL-1: 12748244 — "Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial)" Fukuoka M et al. J Clin Oncol. 2003 Jun 15;21(12):2237-46. IDEAL-2: 14570950 — "Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial." Kris MG et al. JAMA. 2003 Oct 22;290(16):2149-58. Both trials tested 250 mg vs 500 mg daily doses and showed no difference in efficacy but fewer side effects in the low dose arm. Erlotinib (Tarceva) Is a tyrosine kinase inhibitor. NCI Canada Clinical Trials Group trial BR.21 16014882 — "Erlotinib in previously treated non-small-cell lung cancer." Shepherd FA et al. N Engl J Med. 2005 Jul 14;353(2):123-32. 731 pts. Stage IIIB-IV who received 1-2 prior chemotherapy regimens. Randomized to erlotinib vs placebo. Response rate 8.9%. PFS 2.2 vs 1.8 months (placebo), S.S. OS 6.7 vs 4.7 m (HR = 0.7). TRIBUTE trial 16043829 — "TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non-Small-Cell Lung Cancer." Herbst RS et al. J Clin Oncol. 2005 Sep 1;23(25):5892-9.p 1059 pts. Stage IIIB/IV. Randomized. Received 6 cycles of carboplatin and paclitaxel, combined with erlotinib vs placebo. No difference in OS or TTP. Pts who never smoked had improved OS with erlotinib, 22 vs 10 months. Predictors of response: 16043828 — "Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non-Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib." Eberhard DA et al. J Clin Oncol. 2005 Sep 1;23(25):5900-9. From TRIBUTE trial, treated with chemotherapy +/- erlotinib. EGFR mutations (in 13%) associated with improved survival in all arms. Among those receiving erlotinib, there is an improved response rate for those with EGFR mutations and a trend toward improved TTP but no difference in survival. K-RAS mutations (21%) associated with decreased TTP and survival.