BackgroundCetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC).MethodsPatients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH).ResultsForty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes.ConclusionsThe addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.

7019 Background: C, an anti-EGFR monoclonal antibody, enhances the efficacy of both RT and CT. We evaluated a novel strategy of RT plus C followed by consolidation CT plus C for the treatment of stage III NSCLC. Methods: Eligible were pts with unresectable stage IIIA or IIIB NSCLC, ECOG performance status (PS) 0-1, no history of pulmonary fibrosis and adequate end organ function. Pts were treated with chest RT (73.5 Gy in 35 fractions/7 weeks, once daily, with lung and tissue heterogeneity corrections (63 Gy without corrections) and C 250 mg/m2 weekly during RT (after a loading dose of 400 mg/m2 the week prior to starting RT). C was continued after RT completion and during consolidation therapy for 26 weeks. Paclitaxel 200 mg/m2 and carboplatin AUC of 6 were given for 3 cycles (every 3 weeks) after 4-6 weeks from RT. Primary endpoint was the overall survival. Results: Thirty-eight eligible pts were analyzed (2 ineligible pts were excluded from analysis). 25 males; median age 67 yrs; PS 0: 19, PS 1: 19; 14 adenocarcinomas, 10 squamous, 14 non-otherwise specified; Stage: 13 IIIA, 25 IIIB. Median corrected RT dose: 73.5 Gy (56-73.5); median C doses: 18. 33 pts received at least 1 cycle of consolidation. Grade 3/4 toxicities during RT/C were (in > 1 pt): pulmonary embolism (2/2), infection (2/1), fatigue (2/0) and rash (3/0). Grade 3/4 toxicities during consolidation: neutropenia (7/9), neutropenic fever (0/2), lymphopenia (4/0), infection (0/1), rash (2/0). One pt died of pneumonitis, possibly related to C. Best response using RECIST in 31 evaluable pts: 4 CR, 17 PR, 4 SD, 6 PD. With a median follow up of 17.75 months, the median OS and PFS were 17.1 and 9.3 months, respectively. Pts with EGFR positive tumors by FISH (17 of 28 tested) had a trend towards better PFS (p=0.07). Conclusions: C with RT followed by consolidation therapy was associated with acceptable toxicities and efficacy comparable to RT/CT. There was no associated grade 3-4 esophagitis. Supported in part by P50 CA090440.

Acute radiation esophagitis is a common complication in the treatment of lung malignancies which can lead to treatment interruption and undesirable morbidity. We report our experience treating locally-advanced non-small cell lung cancers using chemoradiotherapy via IMRT and the associated acute treatment-related toxicities, and we determined potential dosimetric parameters predictive for acute esophagitis. This retrospective, multi-site study assessed 37 Stage IA-IV lung cancer patients who received IMRT. All patients were scanned during free breathing using coached retrospective 4D-CT and 21 had phase-based gated treatment delivery. A median dose of 70.0 Gy (range: 50 - 81.9 Gy) over 35 fractions (range 25 - 39 fractions) was delivered to the tumor using inhomogeneity correction. The esophagus was contoured and the mean dose and the volume of esophagus receiving 30, 50, 60 and 70 Gy (V30, V50, V60, V70, respectively) was calculated for each patient. Patients were graded for acute and chronic toxicities using the CTCAE 3.0 and logistic regression was performed to test associations between dosimetric parameters and esophageal toxicity. All simulated patients completed their course of chemoradiotherapy treatment. Twenty-eight patients (76%) received radiation treatment with concurrent chemotherapy. The most common acute toxicities were nausea, esophagitis, and fatigue observed in 11, 26, and 18 patients respectively. Only 3 patients (8%) developed Grade 3 radiation pneumonitis confirmed clinical and radiographically and required treatment with oral steroids. Acute Grade 1, 2 and 3 nausea was observed in 5, 4 and 2 patients; acute Grade 1, 2 and 3 esophagitis was observed in 8, 17 and 1 patients and acute Grade 1, 2 and 3 fatigue was observed in 9, 7 and 2 patients, respectively. Patients who experienced any esophagitis had a mean dose in excess of 28.7 Gy to the esophagus (Odds ratio: 1.09, 95% confidence interval: 1.02 - 1.18, p = 0.01). Univariate logistic regression correlated acute Grade ≥2 esophagitis with V60 (p = 0.045) and mean esophageal dose (p = 0.049). We did not identify significant differences in acute esophagitis between patients receiving concurrent chemotherapy and radiation versus those receiving radiation alone (p = 0.058). We were not able to correlate any parameters with late/chronic esophagitis. The mean dose to the esophagus and the volume of esophagus receiving higher doses of irradiation, but not chemotherapy, are associated with the development of esophagitis. Maintaining a mean doses to the esophagus below 28.7 Gy and restricting the volume of esophagus receiving 60 Gy or more can help to minimize treatment associated esophagitis.

Recently a new isotope, Cesium 131, has been introduced for use in prostate brachytherapy in hopes of decreasing the duration of the bothersome urinary and bowel side effects which occur after the procedure. The present study evaluates the severity and time to resolution of acute urinary and bowel symptoms in men undergoing prostate brachytherapy with Cesium 131. All patients undergoing prostate brachytherapy with Cesium 131 at our institution were asked to complete the Expanded Prostate Cancer Index Composite (EPIC) pre-operatively and at 2 weeks, 4 weeks, 2 months, 3 months, and 6 months postoperatively. Patients who have completed at least 2 EPIC surveys were included in this study. Student's t test was used for comparing the difference between the means. To date, 94 patients have undergone prostate brachytherapy with Cesium 131. 79 patients had at least 2 completed EPIC surveys. The mean EPIC urinary scores at baseline, 2 weeks, 4 weeks, 2 months, 3 months, and 6 months were 84.77, 58.69, 62.82, 66.06, 79.03, 87.03, respectively. The mean EPIC bowel scores at baseline, 2 weeks, 4 weeks, 2 months, 3 months and 6 months were 83.86, 51.44, 56.72, 62.46, 80.12, 84.8, respectively. Urinary and bowel summary scores were significantly different from baseline at 2 weeks, 4 weeks and 2 months. The bowel and urinary summary scores returned to baseline at 3 and 6 months, respectively. Similarly all the bowel subscales including function and bother returned to baseline at 3 months. Urinary subscales including function, bother, incontinence and irritative symptoms returned to baseline at 6 months. In patients undergoing prostate brachytherapy with Cesium 131, postoperative bowel and urinary symptoms peaked between 2 to 4 weeks and returned to baseline at 3 and 6 months, respectively. The symptom scores suggest early peak and decreased duration of symptoms probably because of shorter half life of Cesium 131 radioisotope.

6051 Background: E is a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor that may enhance the efficacy of RT and chemotherapy. Our goal was to incorporate E in the induction and subsequent chemoradiotherapy of HNSCC. We report our preliminary results with TPE induction. Methods: Patients (pts) had pathologically documented HNSCC stage III/IV or selected stage II (base of tongue, hypopharynx, or nasopharynx), no prior therapy, ECOG PS 0–1, and adequate hematologic, kidney and liver laboratory parameters. Induction consisted of T 75 mg/m2 day 1, P 75 mg/m2 day 1, and E 250 mg/m2 days 1,8, and 15 (after an initial dose of 400 mg/m2 on cycle 1, day 1), repeated every 21 days × 3 cycles. Subsequently, pts received RT 70 Gy (2 Gy/day) with concurrent P 30 mg/m2 and E 250 mg/m2 weekly, followed by maintenance E for 6 months. Prophylactic antibiotics were given on days 5–14 of each TPE cycle. Tumor assessment was performed after induction (primary endpoint) and 8 weeks after RT. Sample size was 39; one-stage design; target overall response rate (ORR): 80%. Results: 21 pts have been enrolled to date: median age 55 (39–74); Male/Female: 18/3; primary site: oropharynx (n=13), larynx (n=5), and other (n=3); stage III/IV: 4/17. In 16 evaluable pts, ORR to TPE was 15/16 (94%), CR: 2, PR 13, SD 1. For the primary site (12 evaluable): CR 6, PR 5, SD 1; for the lymph nodes (14 evaluable): CR 1, PR: 12, SD 1. The pt with SD discontinued E in the first cycle due to recurring infusion reaction. Another patient had a grade (G) 3 infusion reaction on the first E administration and was removed from study. Other serious toxicities during TPE (n=20): grade (G) 3/4 neutropenia (n=4/n=7) without incidence of neutropenic fever, G 3 anemia (n=1), G 3 thrombocytopenia (n=1), G 3/4 hypomagnesemia (n=2/n=1), G 3 rash (n=1), G 3 fatigue (n=4), and G 3 diarrhea (n=1). 1 pt had sudden death due to myocardial infarction (autopsy) after the third cycle of TPE. Subsequent RT plus P and E was feasible. 10 pts completed RT and all remain progression-free. Conclusions: Preliminary results suggest that TPE has predictable and manageable toxicities and high activity in HNSCC. Accrual is ongoing and updated data will be available. No significant financial relationships to disclose.