Background We designed a phase i study of concurrent chemoradiotherapy (ccrt) with docetaxel (D) and cisplatin (C), followed by consolidation dc, for unresectable stage iii non-small cell lung cancer (nsclc). Methods Patients with histologically proven and unresectable stage iii nsclc were eligible. During ccrt, C was given every 3 weeks (75 mg/m2) and D given weekly. The starting dose of D was 20 mg/m2, escalated in cohorts of 3 to define the maximum tolerated dose (mtd). Radiotherapy was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidation dc, which were dose escalated if ccrt was tolerated. Results Twenty-six patients were enrolled, with 1 excluded following evidence of metastatic disease. Nineteen patients completed both phases of treatment. There were 7 grade 3 events during ccrt (5 esophagitis, 2 nausea), and 8 grade 3 events during consolidation (2 neutropenia, 2 leukopenia, 1 esophagitis, 2 nausea, and 1 pneumonitis). Three patients had grade 4 neutropenia. No patients died due to toxicities. The mtd of concurrent weekly D was 20 mg/m2. Consolidation D and C were each dose escalated to 75 mg/m2 in 8 patients. The median overall survival (os) and progression-free survival (pfs) of all patients were 33.6 months and 17.2 months, respectively, with median follow-up of 26.6 months (range 0.43-110.8). Conclusions The use of docetaxel 20 mg/m2 weekly and cisplatin 75 mg/m2 every 3 weeks concurrent with thoracic radiotherapy, followed by consolidation docetaxel and cisplatin, both given at 75 mg/m2 every 3 weeks, appears to be safe in this phase i trial.

The current standard of care for unresectable locally advanced stage III non-small cell lung cancer (NSCLC) is chemoradiation therapy. However, there is no established consensus for the optimal chemotherapy regimen. We designed a phase I study of docetaxel and cisplatin (DC) chemotherapy with concurrent thoracic radiation therapy (RT) followed by consolidative DC for locally advanced NSCLC. The primary objective of this study is to determine optimal concurrent and consolidative DC doses, with secondary objectives to describe associated toxicities. Patients with histologically or cytologically proven and unresectable Stage IIIA or IIIB (dry) NSCLC were eligible for this single-institution research-ethics board approved study. In the concurrent cycles with thoracic RT, C was given every 3 weeks (fixed at 75mg/m2) and D given weekly. The starting dose of D was 20mg/m2 weekly escalated in cohorts of 3 to define the maximum tolerated dose. RT was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidative DC, which were dose escalated if concurrent chemoradiation therapy was tolerated. Evaluation for dose limiting toxicities was performed on a weekly basis during RT. Tumor response was characterized through the RECIST criteria. Actuarial outcomes of overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier analysis. Between September 2004 and June 2014, 26 patients were enrolled. One patient did not receive protocol-specified treatment due to metastatic disease on baseline staging investigations. Of the eligible patients, 18 had stage IIIA and 7 had stage IIIB disease. The median OS of all patients was 33.6 months (95% CI 15.8-71.6). Median PFS was 17.0 months (95% CI 9.2-26.3) with median follow-up of 26.6 months (range 0.43-110.8). The majority of patients (19/26) completed both phases of treatment and most received concurrent D at 20mg/m2 weekly. Eight patients tolerated dose escalation of posterior consolidative C or D. Twelve patients experienced grade 3 toxicities (5 esophagitis, 1 pneumonitis, 3 nausea, 1 leukopenia, and 2 neutropenia). Three patients had grade 4 neutropenia. No patients died due to early or late treatment toxicities. Complete response, partial response, and stable disease were observed in 1, 16, and 4 patients, respectively. Five patients underwent surgical resection, and 3 of 5 did not have evidence of residual disease. Cisplatin and docetaxel (DC) chemotherapy with concurrent radiation treatment followed by consolidative DC achieved promising results in the treatment of stage III NSCLC in light of reported outcomes from RTOG 0617 (standard arm median PFS 11.8, OS 28.7 months). However, treatment toxicities should be considered. The dose finding results of this study will inform the design of phase II/III trials.

Aims: Uncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer. Systematic reviews and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000, respectively. The systematic reviews were updated and revised and new recommendations for preoperative and postoperative therapy were developed based on the updated body of evidence. The following research questions were addressed: After appropriate preoperative staging tests, should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy (with or without chemotherapy)? What is the role of postoperative radiotherapy and/or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, in terms of improving survival and delaying local recurrence?Materials and methods: The MEDLINE, EMBASE and Cochrane Library databases, as well as meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer. The draft practice guideline and systematic reviews were distributed through a mailed survey to 129 health care providers in Ontario for review.Results: Systematic reviews on preoperative and postoperative therapy for rectal cancer were developed. On the basis of the evidence contained in these reviews, the Gastrointestinal Cancer Disease Site Group drafted recommendations. Of the 33 practitioners who responded to the mailed survey, 97% agreed with the draft recommendations as stated, 88% agreed that the report should be approved as a practice guideline and 94% indicated that they were likely to use the guideline in their own practice.Conclusions: Preoperative chemoradiotherapy is preferred, compared with standard fractionation preoperative radiotherapy alone, to decrease local recurrence. Preoperative chemoradiotherapy is also preferred, compared with a postoperative approach, to decrease local recurrence and adverse effects. For patients with relative contraindications to chemotherapy in the preoperative period, an acceptable alternative is preoperative radiotherapy alone followed by surgery. Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy. (C) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

ObjectivesThe present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (CRT) in high-risk esophageal cancer patients.Patients and MethodsFrom 1989 to 1999, we followed high-risk resected esophageal cancer patients who had completed postoperative CRT therapy. Patients who relapsed with a disease-free interval of less than 3 months were treated with palliative CRT when appropriate. Patients with a disease-free interval of 3 months or more were treated with best supportive care. Post-recurrence survival was estimated using the Kaplan-Meier technique, and statistical comparisons were made using log-rank chi-square tests and Cox regression.ResultsOf the 69 patients treated with adjuvant CRT after esophagectomy, 46 experienced recurrence. Median time to relapse was 28 months (range: 0.1-40 months). Among the 46 relapsed patients, median age was 61 years (range: 37-82 years), and 42 were men. At the initial staging, 44 of 46 were node-positive; 31 of 46 had adenocarcinoma. In 33 of 46, post-esophagectomy resection margins were clear. Median follow-up after recurrence was 30.5 months (range: 1.3-100 months). Median overall survival after recurrence was 5.8 months, and the 12-month, 24-month, and 36-month survival rates were 20%, 10%, and 5% respectively. Of the prognostic factors analyzed, only resection margin status and interval to recurrence were statistically significant for patient outcome in univariate and multivariate analysis. Patients who had positive resection margins and who relapsed 12 or fewer months after surgery and adjuvant CRT had a median post-recurrence overall survival of 0.85 months as compared with 6.0 months in other patients (more than 12 months to relapse, or negative resection margins, or both; log-rank p = 0.003).ConclusionsResection margin status and interval to disease relapse are significant independent prognostic factors for patient outcome after adjuvant CRT therapy.

Background and Purpose: Extended-volume external-beam radiation therapy (rt) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume rt treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. Patients and Methods: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume rt. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3–4, N0–1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous rt were excluded. All 15 study patients received 4 cycles of 5-fluorouracil–based chemotherapy. External-beam rt was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The rt was delivered concurrently with the third cycle of chemotherapy. The study outcomes—disease-free survival (dfs) and overall survival (os)—were calculated by the Kaplan–Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute’s Common Toxicity Criteria. Results: The study accrued 10 men and 5 women of median age 64 years (range: 48–80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5–53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median dfs was 23 months, and the median os was 21 months. Conclusions: Extended-volume external-beam rt encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3–4, N0–1 esophageal cancer patients after esophagectomy.

Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population. Patients and Methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm. Results: Median survival was 7.8 months, and at last follow-up, 3 patients (8.6%) were alive and well, 6 patients (17.1%) were alive and with disease, 24 patients (68.6%) had died of disease, and 2 patients (5.7%) had died of other causes. Univariate analysis demonstrated that lung surgery (P = .0033), primary lung treatment > 8 weeks after brain surgery (P = .0128), and stage I/II disease (P = .0467) were predictive of overall survival. Conclusion: Survival remains poor for patients with NSCLC with an SSBM. However, patients with thoracic disease amenable to local resection should be considered for such therapy because a survival advantage could exist compared with patients with more locally advanced disease.

14560 Background: The oral fluoropyrimidine X (Xeloda®) has efficacy, safety and convenience benefits vs. 5-FU/LV in adjuvant / first-line CRC. E (Tarceva®) inhibits epidermal growth factor receptor (EGFR), which predicts poor prognosis. A randomized open-label phase II study was performed to establish activity of X alone vs. X + E (XE) in first-line. Methods: Pts (ECOG PS 0–2 and/or elevated LDH) with MCRC not eligible for immediate surgical metastatectomy and unwilling/unable to undergo combination chemotherapy were randomized to X (1000mg/m2/d bid d1–14 q3w) or XE (X 1000mg/m2/d bid d1–14 q3w + E 150mg/d). A third arm (E alone) was included but dropped after 13 pts, following safety committee review of progressions at first CT scan. Primary endpoint: time to progression (TTP). Results: 59 pts (median age 65y, range 46–84; 44 M, 15 F) have been accrued (X=21; XE=25; E=13). Mean time on study: 3.8 months (range 0.2–12). 9 pts are on active treatment, 21 pts on follow-up and 29 pts have died. Interim efficacy results are available for 50 pts (X n=15; XE n=22, E n=13). There were no significant differences in response rate, median TTP (4.9 vs. 9.2 months) and median overall survival (18.2 vs. 15.1 months) for X vs. XE. Grade 3 adverse events (AEs) with X were diarrhea, nausea, hand-foot syndrome (HFS), angina, dyspnea (all 5%). Corresponding rates of grade 3 AEs with XE were diarrhea (20%), fatigue (16%), stomatitis (12%), HFS (8%), vomiting (8%), dehydration (8%), thrombosis, weight loss, decreased appetite, dry eyes, headache, anxiety, abdominal pain, anorexia, hyponatremia (all 4%). The only grade 4 AEs were skin rash (4%) and subjective weakness (4%) - both XE. Conclusions: Interim results indicate that XE is at least as effective as X alone in first-line MCRC. Recruitment is continuing and further follow-up may help fully determine the potential benefits of adding E to X. [Table: see text] No significant financial relationships to disclose.

3577 Background: Combination chemotherapy results in improved outcomes in trials of selected fit patients with ACRC. For older, less fit, more complicated patients, combination chemotherapy is associated with greater toxicity and less benefit. Sequential monotherapy is a reasonable option for these patients. Methods: A multicentre phase I/II trial of capecitabine (Xeloda) 2000mg/m2 d1–14 q21d was conducted in 214 patients in one or more of the following subsets: age≥65 years (167 pts), ECOG performance status ≥1 (139 pts), elevated LDH (105 pts), prior pelvic radiation (54 pts), liver enzyme abnormalities (5 pts). Results: Median age was 72 years (range 38 to 90). At a median follow-up of 7.2 months, 131 patients are alive. A median 4 and mean 6.5 cycles were given (range 1 to 33). Prior pelvic radiation required dose reduction to 1500mg/m2 for diarrhea in the 3rd cycle. Of 192 patients evaluable for toxicity, there were no grade 3/4 hematologic toxicities. Grade 3/4 toxicity occurred in 22% of patients d...

The role of fluorouracil and folinic acid and adjuvant therapy for colon cancer is not clear. We undertook independently three randomised trials to find out the efficacy of fluorouracil and high-dose folinic acid after surgery for Dukes' B and C stage colon cancer. The three studies by the Gruppo Interdisciplinare Valutazione Interventi Oncologia (GIVIO), the National Cancer Institute Canada Clinical Trials Group (NCIC-CTG), and the Fondation Francaise de Cancerologie Digestive (FFCD) were pooled for combined analysis.Each trial was multicentre and used the same treatment regimen (fluorouracil 370-400 mg/m(2) plus folinic acid 200 mg/m(2) daily for 5 days, every 28 days for 6 cycles). A pooled analysis of the results was done on the basis of a previously agreed protocol when there were sufficient events to detect at least a 10% reduction in mortality with 80% power. 1526 patients with resected B (56%) and C (44%) carcinoma of the colon were enrolled and 1493 were confirmed as eligible. 736 were assigned to the treatment group and 757 to the control group. Fluorouracii/folinic acid significantly reduced mortality by 22% (95% Cl 3-38; p=0.029) and events by 35% (22-46; p<0.0001), increasing 3-year event-free survival from 62% to 71% and overall survival from 78% to 83%. Compliance with treatment was good; more than 80% of patients completed the planned treatment. Side-effects were clinically acceptable with only 1 treatment-related death. The commonest side-effects were gastrointestinal, but severe toxic effects (WHO grade 4) occurred in fewer than 3% of cases.We conclude that fluorouracil plus high-dose folinic acid is a well-tolerated and effective 6-month adjuvant regimen for colon cancer.